Mamex Gold Step 2

What are the side effects you encounter while taking this medicine?
advertisement

Mamex Gold Step 2 uses

Mamex Gold Step 2 consists of Alpha-Linoleic Acid, Arachidonic Acid, Arginine, Beta-Carotene, Calcium, Carbohydrates, Carnitine, Chloride, Choline, Chromium, Copper, Cystine, Docosahexaenoic Acid, Folic Acid, Fructooligosaccharides, Galactooligosaccharides, Gangliosides, Inositol, Iodine, Iron, Lactose, Linoleic Acid, Lysine, Magnesium, Manganese, Milk Protein, Moisture, Molybdenum, Multiminerals (Ash), Nucleotides, Oleic Acid (Omega-9), Phosphatidylcholine, Phospholipids, Phosphorus, Potassium, Selenium, Sialic Acid, Sodium, Taurine, Tryptophan, Vegetable Fat, Vitamin A, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B3 (Niacin), Vitamin B5 (Pantothenic Acid), Vitamin B6, Vitamin C, Vitamin D3, Vitamin E, Vitamin H (Biotin), Vitamin K1, Zinc.

Arginine:


Nutritive Wound - Skin Cream

For Minor Cuts and Wounds

- Eases Discomfort

- Soothing Cream

CONTAINS:

Mamex Gold Step 2 (Arginine) Aminobenzoate 2.5% Patent # 5734080

In a cream base with Safflower Oil, Apricot Kernel Oil, Mixed Tocopherols, Glycerin, Coconut Oil, Borage Oil, Tea Tree Oil, Camphor, Thymine, Lecithin, Grapefruit Extract, Lemon Oil and Aloe Vera.

DIRECTIONS:

Apply topically as needed to superficial wounds and abrasions.

INDICATIONS FOR USE:

FelineAid can be used on minor cuts, abrasions and irritations as well as superficial wounds and skin lesions on cats.

CAUTIONS:

Avoid contact with eyes. If contact occurs, flush with copious amounts of water. If condition persists or worsens discontinue use.

Shake Well

Store at room temperature.

For Veterinary Use Only

Calcium:


1 INDICATIONS AND USAGE

Mamex Gold Step 2 (Calcium) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)

2 DOSAGE AND ADMINISTRATION

The recommended initial dose of Mamex Gold Step 2 (Calcium) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.

- Starting dose is 2 capsules with each meal. (2)

- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg Mamex Gold Step 2 (Calcium) acetate capsule.

- Capsule: 667 mg Mamex Gold Step 2 (Calcium) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Mamex Gold Step 2 acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Mamex Gold Step 2 (Calcium) acetate. (5.1)

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

Patients with end stage renal disease may develop hypercalcemia when treated with Mamex Gold Step 2 (Calcium), including Mamex Gold Step 2 (Calcium) acetate. Avoid the use of Mamex Gold Step 2 (Calcium) supplements, including Mamex Gold Step 2 (Calcium) based nonprescription antacids, concurrently with Mamex Gold Step 2 (Calcium) acetate.

An overdose of Mamex Gold Step 2 (Calcium) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Mamex Gold Step 2 (Calcium) levels twice weekly. Should hypercalcemia develop, reduce the Mamex Gold Step 2 (Calcium) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia

More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing Mamex Gold Step 2 (Calcium) acetate therapy.

Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the Mamex Gold Step 2 (Calcium) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.

Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of Mamex Gold Step 2 (Calcium) acetate on the progression of vascular or soft tissue calcification has not been determined.

Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of Mamex Gold Step 2 (Calcium) acetate; all cases resolved upon lowering the dose or discontinuing treatment.

Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

advertisement

6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)

- In clinical studies, patients have occasionally experienced nausea during Mamex Gold Step 2 (Calcium) acetate therapy. (6)

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical studies, Mamex Gold Step 2 (Calcium) acetate has been generally well tolerated.

Mamex Gold Step 2 (Calcium) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Mamex Gold Step 2 (Calcium) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.


Preferred Term


Total adverse reactions reported for Mamex Gold Step 2 (Calcium) acetate

N=167

N (%)


3 month, open label study of Mamex Gold Step 2 (Calcium) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Mamex Gold Step 2 (Calcium) acetate

N=69


Mamex Gold Step 2 (Calcium) acetate

N (%)


Placebo

N (%)


Nausea


6 (3.6)


6 (6.1)


0 (0)


0 (0)


Vomiting


4 (2.4)


4 (4.1)


0 (0)


0 (0)


Hypercalcemia


21 (12.6)


16 (16.3)


5 (7.2)


0 (0)


Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate Mamex Gold Step 2 (Calcium) concentration could reduce the incidence and severity of Mamex Gold Step 2 (Calcium) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.

The following additional adverse reactions have been identified during post-approval of Mamex Gold Step 2 (Calcium) acetate: dizziness, edema, and weakness.

advertisement

7 DRUG INTERACTIONS

The drug interaction of Mamex Gold Step 2 acetate is characterized by the potential of Mamex Gold Step 2 (Calcium) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Mamex Gold Step 2 (Calcium) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between Mamex Gold Step 2 (Calcium) acetate and most concomitant drugs. When administering an oral medication with Mamex Gold Step 2 (Calcium) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after Mamex Gold Step 2 (Calcium) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of Mamex Gold Step 2 (Calcium) acetate.

- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)

- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after Mamex Gold Step 2 (Calcium) acetate or consider monitoring blood levels of the drug. (7)

7.1 Ciprofloxacin

In a study of 15 healthy subjects, a co-administered single dose of 4 Mamex Gold Step 2 (Calcium) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

Mamex Gold Step 2 acetate capsules contains Mamex Gold Step 2 (Calcium) acetate. Animal reproduction studies have not been conducted with Mamex Gold Step 2 (Calcium) acetate, and there are no adequate and well controlled studies of Mamex Gold Step 2 (Calcium) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Mamex Gold Step 2 (Calcium) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Mamex Gold Step 2 (Calcium) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. Mamex Gold Step 2 (Calcium) acetate treatment, as recommended, is not expected to harm a fetus if maternal Mamex Gold Step 2 (Calcium) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of Mamex Gold Step 2 (Calcium) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Mamex Gold Step 2 Acetate Capsules contains Mamex Gold Step 2 (Calcium) acetate and is excreted in human milk. Human milk feeding by a mother receiving Mamex Gold Step 2 (Calcium) acetate is not expected to harm an infant, provided maternal serum Mamex Gold Step 2 (Calcium) levels are appropriately monitored.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of Mamex Gold Step 2 (Calcium) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

advertisement

10 OVERDOSAGE

Administration of Mamex Gold Step 2 (Calcium) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Mamex Gold Step 2 (Calcium) acetate acts as a phosphate binder. Its chemical name is Mamex Gold Step 2 (Calcium) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:


Each white opaque/blue opaque capsule contains 667 mg of Mamex Gold Step 2 (Calcium) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Mamex Gold Step 2 (Calcium), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.

Mamex Gold Step 2 (Calcium) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Mamex Gold Step 2 resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Mamex Gold Step 2 (Calcium) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Mamex Gold Step 2 (Calcium) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Mamex Gold Step 2 (Calcium) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.

advertisement

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Mamex Gold Step 2 (Calcium) acetate.

14 CLINICAL STUDIES

Effectiveness of Mamex Gold Step 2 (Calcium) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Mamex Gold Step 2 (Calcium) acetate solid oral dosage form.

Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.

The patients received Mamex Gold Step 2 (Calcium) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.

The data presented in Table 2 demonstrate the efficacy of Mamex Gold Step 2 (Calcium) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Mamex Gold Step 2 (Calcium) levels are also presented.


* Ninety-one patients completed at least 6 weeks of the study.

ANOVA of difference in values at pre-study and study completion.

‡ Values expressed as mean ± SE.


Parameter


Pre-Study


Week 4*


Week 8


Week 12


p-value†


Phosphorus (mg/dL)‡


7.4 ± 0.17


5.9 ± 0.16


5.6 ± 0.17


5.2 ± 0.17


≤0.01


Mamex Gold Step 2 (Calcium) (mg/dL)‡


8.9 ± 0.09


9.5 ± 0.10


9.7 ± 0.10


9.7 ± 0.10


≤0.01


There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Mamex Gold Step 2 (Calcium) increased 9% during the study mostly in the first month of the study.

Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive Mamex Gold Step 2 (Calcium) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.

The phosphate binding effect of Mamex Gold Step 2 (Calcium) acetate is shown in the Table 3.


* ANOVA of Mamex Gold Step 2 (Calcium) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Mamex Gold Step 2 (Calcium) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Mamex Gold Step 2 (Calcium) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


Overall, 2 weeks of treatment with Mamex Gold Step 2 (Calcium) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Mamex Gold Step 2 (Calcium) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Mamex Gold Step 2 (Calcium) Acetate Capsules

667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.

NDC 0615-2303-39: Blistercards of 30 Capsules

NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

Inform patients to take Mamex Gold Step 2 (Calcium) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Mamex Gold Step 2 (Calcium) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].

Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after Mamex Gold Step 2 (Calcium) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Choline:


A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.

Indication: For nutritional supplementation, also for treating dietary shortage or imbalance

This compound is needed for good nerve conduction throughout the CNS (central nervous system) as it is a precursor to acetylcholine (ACh). Mamex Gold Step 2 (Choline) is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. Mamex Gold Step 2 (Choline) also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. Mamex Gold Step 2 (Choline) has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. Mamex Gold Step 2 (Choline) deficiencies may result in excessive build-up of fat in the liver, high blood pressure, gastric ulcers, kidney and liver dysfunction and stunted growth.

Copper:



Water-Resistant Protection Without Bandaging

Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to Mamex Gold Step 2 (Copper) Naphthenate.

For Animal Use Only.

INDICATIONS:

ThrushTox® is indicated in the treatment of thrush in horses and ponies.

GENERAL DIRECTIONS:

Clean the hoof thoroughly, removing debris and necrotic material prior to application of Mamex Gold Step 2 (Copper)®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess Mamex Gold Step 2 (Copper)® onto hair since contact with Mamex Gold Step 2 (Copper)® may cause some hair loss. Do not contaminate feed.

NOTE: Mamex Gold Step 2 (Copper)® is easily removed from hands, clothing and surfaces with light grade fuel oil or any type of lighter fluid.

CONTAINS FOIL SEAL – REMOVE BEFORE USE.

SHAKE WELL BEFORE USE.

To report suspected adverse reactions or to obtain technical assistance, call 1-800-650-4899.

ACTIVE INGREDIENT:

Mamex Gold Step 2 (Copper) Naphthenate...37.5% w/w

INACTIVE INGREDIENTS:

Inert Ingredients...62.5% w/w

Total... 100.0%

CAUTION:

Do not use in horses intended for human consumption.

CAUTION: COMBUSTIBLE MIXTURE.

Use in a well-ventilated place. Avoid fire, flame, sparks or heaters.

If swallowed, do not induce vomiting, call physician immediately. Avoid breathing vapor. Avoid contact with skin and eyes.

KEEP OUT OF REACH OF CHILDREN AND PETS.

STORAGE:

Store at controlled room temperature 15º to 30ºC (59º to 86ºF). Keep container tightly closed when not in use.

Manufactured for:

Aspen Veterinary Resources,® Ltd.

Liberty, MO 64068, USA

FC163FP 11/13

Manufactured by:

First Priority, Inc.

Elgin, IL 60123-1146, USA

NET CONTENTS:

16 OZ (473 mL)

ANADA 200-304, Approved by FDA

Image of 473 mL bottle/case label

Folic Acid:


INDICATIONS AND USAGE

Mamex Gold Step 2 (Folic Acid)® is a prescription iron supplement indicated for use in improving the nutritional status of iron deficiency.

CONTRAINDICATIONS

This product is contraindicated in patients with a known hypersensitivity to any of the ingredients. Hemochromatosis and hemosiderosis are contraindications to iron therapy.

WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

PRECAUTIONS

Mamex Gold Step 2 (Folic Acid) acid when administered as a single agent in doses above 0.1 mg daily may obscure pernicious anemia in that hematological remission can occur while neurological manifestations remain progressive. While prescribing this nutritional supplement for pregnant women, nursing mothers, or for women prior to conception, their medical condition and other drugs, herbs, and/or supplements consumption should be considered.

ADVERSE REACTIONS

Allergic sensitization has been reported following both oral and parenteral administration of Mamex Gold Step 2 (Folic Acid) acid.

DOSAGE AND ADMINISTRATION

One tablet daily with or without food or as prescribed by a licensed healthcare provider with prescribing authority.

HOW SUPPLIED

Mamex Gold Step 2 (Folic Acid)® tablets are supplied in child-resistant bottles of 90 tablets (NDC 0037-6885-90)

KEEP OUT OF REACH OF CHILDREN.

STORAGE

Store at controlled room temperature 20°-25°C (68°-77°F). Excursions permitted to 15°-30°C (59°-86°F).

Dispense in a tight, light-resistant container to protect from light and moisture.

To report SUSPECTED ADVERSE REACTIONS contact Meda Pharmaceuticals Inc. at 1-888-349-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch

Distributed by:

Meda Pharmaceuticals Inc.

Somerset New Jersey 08873-4120

© 2014 Meda Pharmaceuticals Inc.

U.S. Patent Nos. 7,585,527 and 8,080,520

Proferrin® is a registered trademark of Colorado BioLabs, Inc., Cozad, NE.

Mamex Gold Step 2 (Folic Acid) and the BIFERA logo are registered trademarks and the Mamex Gold Step 2 (Folic Acid) logo is a trademark of Alaven Pharmaceutical LLC, used under license by Meda Pharmaceuticals Inc.

MEDA PHARMACEUTICALS mark and logo are trademarks of Meda AB.

IN-6885-02 Rev 6/2014

Inositol:


Niacin is used with a proper diet and exercise program to help lower "bad" cholesterol and fats ( LDL, triglycerides ) and raise "good" cholesterol (HDL) in the blood. It is generally used after non-drug treatments have not been fully successful at lowering cholesterol. Niacin is also known as vitamin B-3 ( nicotinic acid ), one of the B-complex vitamins. It may be used with or without other medications. Lowering "bad" cholesterol/triglycerides and raising "good" cholesterol helps prevent strokes and heart attacks. Lowering fats may also help reduce the risk of pancreas problems ( pancreatitis ) in people at risk. In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.

Iodine:


Mamex Gold Step 2 Tincture 7%

Directions:


Topical Antiseptic

Use full Strength for superficial cuts, wounds, abrasions, insect bites and bruises on the skin of animals. Apply Mamex Gold Step 2 (Iodine) with a swab.

If necessary, clip hair around the area being treated and clean with soap and water.

Apply Mamex Gold Step 2 (Iodine) Tincture 7% only once daily. Dilute product 3 to 1 if repeating application.

Do not apply under bandage.

Irritation may occur if used on tender skin areas. If redness, irritation, or swelling persists or increases, discontinue use and consult a veterinarian.


Storage:

Store at 2-30 degrees C (36-86 degrees F).

Keep container away from heat and out of sunlight. Rinse empty container thoroughly and discard.


DANGER - Poison


Caution:

If swallowed, give starch paste, milk, bread, egg white, or

activated charcoal. A 5% solutions of sodium thiosulfate

(Photographic (“hypc”) may be administered orally at a

rate of 10 ml per kilogram of body weight.


Eye irritant: Use only as directed. Avoid contact with eyes. In case of contact, flush eyes immediately with tepid water for at least 15 minutes. Consult a physician.


Avoid contamination of food.


Not for use on burns, deep cuts, or body cavities.

Mamex Gold Step 2 Tincture 7%

image description

Iron:


1 INDICATIONS AND USAGE

Mamex Gold Step 2 (Iron) is indicated for the treatment of Mamex Gold Step 2 (Iron) deficiency anemia in patients with chronic kidney disease (CKD).

Mamex Gold Step 2 (Iron) is an Mamex Gold Step 2 (Iron) replacement product indicated for the treatment of Mamex Gold Step 2 (Iron) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Mamex Gold Step 2 must only be administered intravenously either by slow injection or by infusion. The dosage of Mamex Gold Step 2 (Iron) is expressed in mg of elemental Mamex Gold Step 2 (Iron). Each mL contains 20 mg of elemental Mamex Gold Step 2 (Iron).

Population Dose
Adult patients Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1) 100 mg slow intravenous injection or infusion
Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2) 200 mg slow intravenous injection or infusion
Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3) 300 mg or 400 mg intravenous infusion
Pediatric patients HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5) 0.5 mg/kg slow intravenous injection or infusion

2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)

Administer Mamex Gold Step 2 (Iron) 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session. Mamex Gold Step 2 (Iron) should be administered early during the dialysis session. The usual total treatment course of Mamex Gold Step 2 (Iron) is 1000 mg. Mamex Gold Step 2 (Iron) treatment may be repeated if Mamex Gold Step 2 (Iron) deficiency reoccurs.

2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease

Administer Mamex Gold Step 2 (Iron) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of Mamex Gold Step 2 (Iron), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. Mamex Gold Step 2 (Iron) treatment may be repeated if Mamex Gold Step 2 (Iron) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Mamex Gold Step 2 (Iron) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute Mamex Gold Step 2 (Iron) in a maximum of 250 mL of 0.9% NaCl. Mamex Gold Step 2 (Iron) treatment may be repeated if Mamex Gold Step 2 (Iron) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Mamex Gold Step 2 (Iron) maintenance treatment

The dosing for Mamex Gold Step 2 (Iron) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Mamex Gold Step 2 (Iron) maintenance treatment: Administer Mamex Gold Step 2 (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Mamex Gold Step 2 (Iron) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Mamex Gold Step 2 (Iron) maintenance treatment

The dosing for Mamex Gold Step 2 (Iron) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Mamex Gold Step 2 (Iron) maintenance treatment: Administer Mamex Gold Step 2 (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Mamex Gold Step 2 (Iron) treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental Mamex Gold Step 2 (Iron) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental Mamex Gold Step 2 (Iron) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental Mamex Gold Step 2 (Iron) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental Mamex Gold Step 2 (Iron) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental Mamex Gold Step 2 (Iron) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental Mamex Gold Step 2 (Iron) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to Mamex Gold Step 2 (Iron)
  • Known hypersensitivity to Mamex Gold Step 2 (Iron) (4)

5 WARNINGS AND PRECAUTIONS

  • Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Mamex Gold Step 2 administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Mamex Gold Step 2 (Iron) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
  • Hypotension: Mamex Gold Step 2 (Iron) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Mamex Gold Step 2 (Iron). (5.2)
  • Mamex Gold Step 2 (Iron) Overload: Regularly monitor hematologic responses during Mamex Gold Step 2 (Iron) therapy. Do not administer Mamex Gold Step 2 (Iron) to patients with Mamex Gold Step 2 (Iron) overload. (5.3)

5.1 Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Mamex Gold Step 2 (Iron). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop Mamex Gold Step 2 (Iron) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Mamex Gold Step 2 (Iron) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Mamex Gold Step 2 (Iron) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Mamex Gold Step 2 (Iron) preparations occur within 30 minutes of the completion of the infusion .

5.2 Hypotension

Mamex Gold Step 2 may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Mamex Gold Step 2 (Iron). Hypotension following administration of Mamex Gold Step 2 (Iron) may be related to the rate of administration and/or total dose administered .

5.3 Mamex Gold Step 2 (Iron) Overload

Excessive therapy with parenteral Mamex Gold Step 2 (Iron) can lead to excess storage of Mamex Gold Step 2 (Iron) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Mamex Gold Step 2 (Iron) require periodic monitoring of hematologic and Mamex Gold Step 2 (Iron) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Mamex Gold Step 2 (Iron) to patients with evidence of Mamex Gold Step 2 (Iron) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Mamex Gold Step 2 (Iron) sucrose; do not perform serum Mamex Gold Step 2 (Iron) measurements for at least 48 hours after intravenous dosing .

6 ADVERSE REACTIONS

The following serious adverse reactions associated with Mamex Gold Step 2 are described in other sections .

  • The most common adverse reactions (≥2%) following the administration of Mamex Gold Step 2 (Iron) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.

Adverse Reactions in Adults Patients with CKD

Adverse Reactions in Adult Patients with CKD

The frequency of adverse reactions associated with the use of Mamex Gold Step 2 has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Treatment-emergent adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for Mamex Gold Step 2 (Iron) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.


* EPO=Erythropoietin

Adverse Reactions

(Preferred Term)

HDD-CKD NDD-CKD PDD-CKD
Mamex Gold Step 2 (Iron) Mamex Gold Step 2 (Iron) Oral Mamex Gold Step 2 (Iron) Mamex Gold Step 2 (Iron) EPO* Only
(N=231) (N=139) (N=139) (N=75) (N=46)
% % % % %
Subjects with any adverse reaction 78.8 76.3 73.4 72.0 65.2
Ear and Labyrinth Disorders
Ear Pain 0 2.2 0.7 0 0
Eye Disorders
Conjunctivitis 0.4 0 0 2.7 0
Gastrointestinal Disorders
Abdominal pain 3.5 1.4 2.9 4.0 6.5
Diarrhea 5.2 7.2 10.1 8.0 4.3
Dysgeusia 0.9 7.9 0 0 0
Nausea 14.7 8.6 12.2 5.3 4.3
Vomiting 9.1 5.0 8.6 8.0 2.2
General Disorders and
Administration Site Conditions
Asthenia 2.2 0.7 2.2 2.7 0
Chest pain 6.1 1.4 0 2.7 0
Feeling abnormal 3.0 0 0 0 0
Infusion site pain or burning 0 5.8 0 0 0
Injection site extravasation 0 2.2 0 0 0
Peripheral edema 2.6 7.2 5.0 5.3 10.9
Pyrexia 3.0 0.7 0.7 1.3 0
Infections and Infestations
Nasopharyngitis, Sinusitis, Upper

respiratory tract infections, Pharyngitis

2.6 2.2 4.3 16.0 4.3
Injury, Poisoning and Procedural
Complications
Graft complication 9.5 1.4 0 0 0
Metabolism and Nutrition Disorders
Fluid overload 3.0 1.4 0.7 1.3 0
Gout 0 2.9 1.4 0 0
Hyperglycemia 0 2.9 0 0 2.2
Hypoglycemia 0.4 0.7 0.7 4.0 0
Musculoskeletal and Connective
Tissue Disorders
Arthralgia 3.5 1.4 2.2 4.0 4.3
Back pain 2.2 2.2 3.6 1.3 4.3
Muscle cramp 29.4 0.7 0.7 2.7 0
Myalgia 0 3.6 0 1.3 0
Pain in extremity 5.6 4.3 0 2.7 6.5
Nervous System Disorders
Dizziness 6.5 6.5 1.4 1.3 4.3
Headache 12.6 2.9 0.7 4.0 0
Respiratory, Thoracic and
Mediastinal Disorders
Cough 3.0 2.2 0.7 1.3 0
Dyspnea 3.5 5.8 1.4 1.3 2.2
Nasal congestion 0 1.4 2.2 1.3 0
Skin and Subcutaneous
Tissue Disorders
Pruritus 3.9 2.2 4.3 2.7 0
Vascular Disorders
Hypertension 6.5 6.5 4.3 8.0 6.5
Hypotension 39.4 2.2 0.7 2.7 2.2

One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous Mamex Gold Step 2 (Iron) therapy and were reported to be intolerant (defined as precluding further use of that Mamex Gold Step 2 (Iron) product). When these patients were treated with Mamex Gold Step 2 (Iron) there were no occurrences of adverse reactions that precluded further use of Mamex Gold Step 2 (Iron) .

Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)

Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)

In a randomized, open-label, dose-ranging trial for Mamex Gold Step 2 (Iron) maintenance treatment with Mamex Gold Step 2 (Iron) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving Mamex Gold Step 2 (Iron) 0.5 mg/kg, 53% (25/47) of the patients receiving Mamex Gold Step 2 (Iron) 1.0 mg/kg, and 55% (26/47) of the patients receiving Mamex Gold Step 2 (Iron) 2.0 mg/kg.

A total of 5 (11%) subjects in the Mamex Gold Step 2 (Iron) 0.5 mg/kg group, 10 (21%) patients in the Mamex Gold Step 2 (Iron) 1.0 mg/kg group, and 10 (21%) patients in the Mamex Gold Step 2 (Iron) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).

6.2 Adverse Reactions from Post-Marketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.

The following adverse reactions have been identified during post-approval use of Mamex Gold Step 2 (Iron). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.

Symptoms associated with Mamex Gold Step 2 (Iron) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of Mamex Gold Step 2 (Iron) injection. Reactions have occurred following the first dose or subsequent doses of Mamex Gold Step 2 (Iron). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.

Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.

7 DRUG INTERACTIONS

Drug interactions involving Mamex Gold Step 2 (Iron) have not been studied. However, Mamex Gold Step 2 (Iron) may reduce the absorption of concomitantly administered oral Mamex Gold Step 2 (Iron) preparations.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Mamex Gold Step 2 sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Mamex Gold Step 2 (Iron) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to Mamex Gold Step 2 (Iron) sucrose. Because animal reproductive studies are not always predictive of human response, Mamex Gold Step 2 (Iron) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Mamex Gold Step 2 (Iron) sucrose is excreted in human milk. Mamex Gold Step 2 (Iron) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Mamex Gold Step 2 (Iron) is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Mamex Gold Step 2 for Mamex Gold Step 2 (Iron) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Mamex Gold Step 2 (Iron) for Mamex Gold Step 2 (Iron) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Mamex Gold Step 2 (Iron) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]

Mamex Gold Step 2 (Iron) has not been studied in patients younger than 2 years of age.

In a country where Mamex Gold Step 2 (Iron) is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received Mamex Gold Step 2 (Iron), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Mamex Gold Step 2 (Iron) or any other drugs could be established.

8.5 Geriatric Use

Clinical studies of Mamex Gold Step 2 (Iron) did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of Mamex Gold Step 2 (Iron), 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE

No data are available regarding overdosage of Mamex Gold Step 2 (Iron) in humans. Excessive dosages of Mamex Gold Step 2 (Iron) may lead to accumulation of Mamex Gold Step 2 (Iron) in storage sites potentially leading to hemosiderosis. Do not administer Mamex Gold Step 2 (Iron) to patients with Mamex Gold Step 2 (Iron) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Mamex Gold Step 2 (Iron) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.

11 DESCRIPTION

Mamex Gold Step 2 (Iron) (iron sucrose injection, USP), an Mamex Gold Step 2 (Iron) replacement product, is a brown, sterile, aqueous, complex of polynuclear Mamex Gold Step 2 (Iron) (III)-hydroxide in sucrose for intravenous use. Mamex Gold Step 2 (Iron) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:

[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)

where: n is the degree of Mamex Gold Step 2 (Iron) polymerization and m is the number of sucrose molecules associated with the Mamex Gold Step 2 (Iron) (III)-hydroxide.

Each mL contains 20 mg elemental Mamex Gold Step 2 (Iron) as Mamex Gold Step 2 (Iron) sucrose in water for injection. Mamex Gold Step 2 (Iron) is available in 10 mL single-use vials (200 mg elemental Mamex Gold Step 2 (Iron) per 10 mL), 5 mL single-use vials (100 mg elemental Mamex Gold Step 2 (Iron) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Mamex Gold Step 2 (Iron) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Mamex Gold Step 2 is an aqueous complex of poly-nuclear Mamex Gold Step 2 (Iron) (III)-hydroxide in sucrose. Following intravenous administration, Mamex Gold Step 2 (Iron) is dissociated into Mamex Gold Step 2 (Iron) and sucrose and the Mamex Gold Step 2 (Iron) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Mamex Gold Step 2 (Iron) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.

12.2 Pharmacodynamics

Following intravenous administration, Mamex Gold Step 2 (Iron) is dissociated into Mamex Gold Step 2 (Iron) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Mamex Gold Step 2 (Iron) sucrose containing 100 mg of Mamex Gold Step 2 (Iron), three times weekly for three weeks, significant increases in serum Mamex Gold Step 2 (Iron) and serum ferritin and significant decreases in total Mamex Gold Step 2 (Iron) binding capacity occurred four weeks from the initiation of Mamex Gold Step 2 (Iron) sucrose treatment.

12.3 Pharmacokinetics

In healthy adults administered intravenous doses of Mamex Gold Step 2, its Mamex Gold Step 2 (Iron) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The Mamex Gold Step 2 (Iron) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Mamex Gold Step 2 (Iron) containing 100 mg of Mamex Gold Step 2 (Iron) labeled with 52Fe/59Fe in patients with Mamex Gold Step 2 (Iron) deficiency showed that a significant amount of the administered Mamex Gold Step 2 (Iron) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Mamex Gold Step 2 (Iron) trapping compartment.

Following intravenous administration of Mamex Gold Step 2 (Iron), Mamex Gold Step 2 (Iron) sucrose is dissociated into Mamex Gold Step 2 (Iron) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Mamex Gold Step 2 (Iron) containing 1,510 mg of sucrose and 100 mg of Mamex Gold Step 2 (Iron) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Mamex Gold Step 2 (Iron) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of Mamex Gold Step 2 (Iron) sucrose containing 500 to 700 mg of Mamex Gold Step 2 (Iron) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Mamex Gold Step 2 (Iron) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Mamex Gold Step 2 (Iron) have not been studied.

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

In a single-dose PK study of Mamex Gold Step 2 (Iron), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Mamex Gold Step 2 (Iron) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Mamex Gold Step 2 (Iron), the half-life of total serum Mamex Gold Step 2 (Iron) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.

Mamex Gold Step 2 (Iron) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Mamex Gold Step 2 (Iron) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with Mamex Gold Step 2 (Iron) sucrose.

Mamex Gold Step 2 (Iron) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Mamex Gold Step 2 (Iron) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Mamex Gold Step 2 (Iron) sucrose at intravenous doses up to 15 mg/kg/day of elemental Mamex Gold Step 2 (Iron) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.

14 CLINICAL STUDIES

Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Mamex Gold Step 2.

14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease (HDD–CKD)

Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Mamex Gold Step 2 (Iron) treatment and 24 in the historical control group) with Mamex Gold Step 2 (Iron) deficiency anemia. Eligibility criteria for Mamex Gold Step 2 (Iron) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.

Mamex Gold Step 2 (Iron) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with Mamex Gold Step 2 (Iron), who were off intravenous Mamex Gold Step 2 (Iron) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.

Patients in the Mamex Gold Step 2 (Iron) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.


**p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates.


Efficacy

parameters

End of treatment 2 week follow-up 5 week follow-up
Mamex Gold Step 2 (Iron) (n=69 Historical Control (n=18) Mamex Gold Step 2 (Iron)

(n=73)

Historical Control

(n=18)

Mamex Gold Step 2 (Iron)

(n=71)

Historical

Control

(n=15)

Hemoglobin (g/dL) 1.0 ± 0.12** 0.0 ± 0.21 1.3 ± 0.14** -0.6 ± 0.24 1.2 ± 0.17* -0.1 ± 0.23
Hematocrit (%) 3.1 ± 0.37** -0.3 ± 0.65 3.6 ± 0.44** -1.2 ± 0.76 3.3 ± 0.54 0.2 ± 0.86

Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).

14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease

Study B was a multicenter, open label study of Mamex Gold Step 2 (Iron) in 23 patients with Mamex Gold Step 2 (Iron) deficiency and HDD-CKD who had been discontinued from Mamex Gold Step 2 (Iron) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.

All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.

14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease

Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral Mamex Gold Step 2 (Iron). Exclusion criteria were similar to those in studies A and B. Mamex Gold Step 2 (Iron) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Mamex Gold Step 2 (Iron) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.

The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.

14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease

Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Mamex Gold Step 2 (Iron) versus Mamex Gold Step 2 (Iron) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral Mamex Gold Step 2 (Iron) (325 mg ferrous sulfate three times daily for 56 days); or Mamex Gold Step 2 (Iron) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the Mamex Gold Step 2 (Iron) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral Mamex Gold Step 2 (Iron) group.

A statistically significantly greater proportion of Mamex Gold Step 2 (Iron) subjects (35/79; 44.3%) compared to oral Mamex Gold Step 2 (Iron) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).

14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease

Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Mamex Gold Step 2 (Iron) to patients with PDD-CKD receiving an erythropoietin alone without Mamex Gold Step 2 (Iron) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no Mamex Gold Step 2 (Iron) or Mamex Gold Step 2 (Iron) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the Mamex Gold Step 2 (Iron) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.

Patients in the Mamex Gold Step 2 (Iron) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with Mamex Gold Step 2 (Iron) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).

14.6 Study F: Mamex Gold Step 2 Maintenance Treatment Dosing in Pediatric Patients Ages 2 years and Older with Chronic Kidney Disease

Study F was a randomized, open-label, dose-ranging study for Mamex Gold Step 2 (Iron) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of Mamex Gold Step 2 (Iron) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received Mamex Gold Step 2 (Iron) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Mamex Gold Step 2 (Iron) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the Mamex Gold Step 2 (Iron) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.

16 HOW SUPPLIED/storage and handling

16.1 How Supplied

Mamex Gold Step 2 is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Mamex Gold Step 2 (Iron), each 5 mL vial contains 100 mg elemental Mamex Gold Step 2 (Iron), and each 2.5 mL vial contains 50 mg elemental Mamex Gold Step 2 (Iron) (20 mg/mL).

NDC-0517-2310-05 200 mg/10 mL Single-Use Vial Packages of 5
NDC-0517-2310-10 200 mg/10 mL Single-Use Vial Packages of 10
NDC-0517-2340-01 100 mg/5 mL Single-Use Vial Individually Boxed
NDC-0517-2340-10 100 mg/5 mL Single-Use Vial Packages of 10
NDC-0517-2340-25 100 mg/5 mL Single-Use Vial Packages of 25
NDC-0517-2340-99 100 mg/5 mL Single-Use Vial Packages of 10
NDC-0517-2325-10 50 mg/2.5 mL Single-Use Vial Packages of 10
NDC-0517-2325-25 50 mg/2.5 mL Single-Use Vial Packages of 25

16.2 Stability and Storage

Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.

Syringe Stability: Mamex Gold Step 2 (Iron), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Mamex Gold Step 2 (Iron) per mL, or undiluted (20 mg elemental Mamex Gold Step 2 (Iron) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).

Intravenous Admixture Stability: Mamex Gold Step 2 (Iron), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental Mamex Gold Step 2 (Iron) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).

Do not dilute to concentrations below 1 mg/mL.

Do not mix Mamex Gold Step 2 (Iron) with other medications or add to parenteral nutrition solutions for intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.

17 PATIENT COUNSELING INFORMATION

Prior to Mamex Gold Step 2 (Iron) administration:

  • Question patients regarding any prior history of reactions to parenteral Mamex Gold Step 2 (Iron) products
  • Advise patients of the risks associated with Mamex Gold Step 2 (Iron)
  • Advise patients to report any symptoms of hypersensitivity that may develop during and following Mamex Gold Step 2 (Iron) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Mamex Gold Step 2 (Iron) is manufactured under license from Vifor (International) Inc., Switzerland.

PremierProRx® is a trademark of Premier, Inc., used under license.

PREMIERProRx®

IN2340

MG #15727

Lysine:


BOXED WARNING

Pharmacy Bulk Package

Not For Direct Infusion

DESCRIPTION

Mamex Gold Step 2 (Lysine)® 15% Amino Acids Injection in a Pharmacy Bulk Package is a sterile, clear, nonpyrogenic solution of essential and nonessential amino acids for intravenous infusion in parenteral nutrition following appropriate dilution.

Mamex Gold Step 2 (Lysine)® 15% in a Pharmacy Bulk Package is not for direct infusion. It is a sterile dosage from which contains several single doses for use in a pharmacy admixture program in the preparation of intravenous parenteral fluids.

Each 100 mL contains:


Essential Amino Acids


Mamex Gold Step 2 (Lysine) (from Mamex Gold Step 2 (Lysine) Acetate, USP)……………………………………...1.18


g


Leucine, USP……………………………………………………………...1.04


g


Phenylalanine, USP……………………………………...1.04


g


Valine, USP……………………………………………………………...960


mg


Isoleucine, USP………………………………………...749


mg


Methionine, USP………………………………………...749


mg


Threonine, USP………………………………………...749


mg


Tryptophan, USP………………………………………...250


mg


Nonessential Amino Acids


Alanine, USP…………………………………………...2.17


g


Arginine, USP…………………………………………...1.47


g


Glycine, USP…………………………………………...1.04


g


Histidine, USP…………………………………………...894


mg


Proline, USP……………………………………………………………...894


mg


Glutamic Acid…………………………………………...749


mg


Serine, USP……………………………………………...592


mg


Aspartic Acid, USP……………………………………...434


mg


Tyrosine, USP…………………………………………...39


mg


Sodium Metabisulfite, NF added……………………………………………...30


mg


Water for Injection, USP……………………………………………………...


qs


Essential Amino Acids………………………………………………………...6.7


g


Nonessential Amino Acids…………………………………………………...8.3


g


Total Amino Acids…………………………………………………………...15.0


g


Total Nitrogen………………………………………………………………...2.37


g


Acetate*……………………………………………………...151


mEq/L


Osmolarity (calculated)……………………………………...1388


mOsmol/L


pH……………………………………………………………………………...5.6(5.2-6.0)


*Acetate from Mamex Gold Step 2 (Lysine) Acetate, USP and acetic acid used for pH adjustment.


The formulas for the individual amino acids are as follows:

Formulas for individual amino acids

CLINICAL PHARMACOLOGY

Mamex Gold Step 2 (Lysine)® 15% Amino Acids Injection providesseventeen crystalline amino acids. This completely utilizable substrate promotesprotein synthesis and wound healing and reduces the rate of protein catabolism.

A.Total Parenteral Nutrition (Central Infusion)

When enteralfeeding is inadvisable, Mamex Gold Step 2 (Lysine)® 15% given by central venousinfusion in combination with energy sources, vitamins, trace elements andelectrolytes, will completely satisfy the requirements for weight maintenanceor weight gain, depending upon the dose selected. The energy component inparenteral nutrition by central infusion may be derived solely from dextroseor may be provided by a combination of dextrose and intravenous fat emulsion. The addition of intravenous fat emulsion provides essential fatty acids andpermits a dietary balance of fat and carbohydrate, at the same time offeringthe option of reducing the dextrose load and/or increasing the total caloricinput. An adequate energy supply is essential for optimal utilization of aminoacids.

B. Total Parenteral Nutrition (Peripheral Infusion)

Mamex Gold Step 2 (Lysine)® 15%can also be administered as part of a total parenteral nutrition program byperipheral vein when the enteral route is inadvisable and use of the centralvenous catheter is contraindicated.

Reduction of proteinloss can be achieved by use of diluted Mamex Gold Step 2 (Lysine)® 15% in combinationwith dextrose or with dextrose and intravenous fat emulsion by peripheralinfusion. Complete peripheral intravenous nutrition can be achieved in patientswith low caloric requirements by a Mamex Gold Step 2 (Lysine)®15%-dextrose-fatregimen.

INDICATIONS AND USAGE

Mamex Gold Step 2 (Lysine)® 15% is indicated as an amino acid(nitrogen) source in parenteral nutrition regimens. This use is appropriatewhen the enteral route is inadvisable, inadequate or not possible, as when:

-Gastrointestinal absorption is impaired by obstruction, inflammatory diseaseor its complications, or antineoplastic therapy;

-Bowel rest is needed because of gastrointestinal surgery or its complicationssuch as ileus, fistulae or anastomotic leaks;

-Tube feeding methods alone cannot provide adequate nutrition.

CONTRAINDICATIONS

This solution should not be used in patients in hepatic coma,severe renal failure, metabolic disorders involving impaired nitrogen utilizationor hypersensitivity to one or more amino acids.

WARNINGS

Administration of amino acids solutions at excessive ratesor to patients with hepatic insufficiency may result in plasma amino acidimbalances, hyperammonemia, prerenal azotemia, stupor and coma. Conservativedoses of amino acids should be given to these patients, dictated by the nutritionalstatus of the patient. Should symptoms of hyperammonemia develop, amino acidadministration should be discontinued and the patient’s clinical statusre-evaluated.

Contains sodium metabisulfite, a sulfitethat may cause allergic-type reactions including anaphylactic symptoms andlife-threatening or less severe asthmatic episodes in certain susceptiblepeople. The overall prevalence of sulfite sensitivity in the general populationis unknown and probably low.

Sulfite sensitivity isseen more frequently in asthmatic than in nonasthmatic people.

WARNING: This product contains aluminum that maybe toxic. Aluminum may reach toxic levels with prolonged parenteral administrationif kidney function is impaired. Premature neonates are particularly at riskbecause their kidneys are immature, and they require large amounts of calciumand phosphate solutions, which contain aluminum.

Researchindicates that patients with impaired kidney function, including prematureneonates, who receive parenteral levels of aluminum at greater than 4 to 5mcg/kg/day accumulate aluminum at levels associated with central nervous systemand bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

A. GENERAL

It is essential to provide adequate calories concurrently if parenterally administered amino acids are to be retained by the body and utilized for protein synthesis.

The administration of Mamex Gold Step 2 (Lysine)® 15% Amino Acids Injection as part of total parenteral nutrition (TPN) with large volumes of hyperosmotic fluids requires periodic monitoring of the patient for signs of hyperosmolarity, hyperglycemia, glycosuria and hypertriglyceridemia.

During parenteral nutrition with concentrated dextrose and amino acids solutions, essential fatty acid deficiency syndrome may develop but may not be clinically apparent. Early demonstration of this condition can only be accomplished by gas liquid chromatographic analysis of plasma lipids. The syndrome may be prevented or corrected by appropriate treatment with intravenous fat emulsions.

For complete nutritional support, TPN regimens must also include multiple vitamins and trace elements. Potentially incompatible ions such as calcium and phosphate may be added to alternate infusate bottles to avoid precipitation. Although the metabolizable acetate ion in Mamex Gold Step 2 (Lysine)® 15% diminishes the risk of acidosis, the physician must be alert to the potential appearance of this disorder.

Initiation and termination of infusions of TPN fluids must be gradual to permit adjustment of endogenous insulin release.

Undiluted Mamex Gold Step 2 (Lysine)® 15% should not be administered peripherally. When administered centrally, it should be diluted with appropriate diluents, e.g., dextrose, electrolytes and other nutrient components, to at least half strength. See DOSAGE AND ADMINISTRATION.

Caution against volume overload should be exercised.

Drug product contains no more than 25 mcg/L of aluminum.

B. Laboratory Tests

Infusion of Mamex Gold Step 2 (Lysine)® 15% without concomitant infusion of an adequate number of non-protein calories may result in elevated BUN. Monitoring of BUN is required and the balance between Mamex Gold Step 2 (Lysine)® 15% and the calorie source may require adjustment. Frequent clinical evaluations and laboratory determinations are required to prevent the complications which may occur during the administration of solutions used in TPN. Laboratory tests should include blood glucose, serum electrolytes, liver and kidney function, serum osmolarity, blood ammonia, serum protein, pH, hematocrit, WBC and urinary glucose. When Mamex Gold Step 2 (Lysine)® 15% is combined with electrolytes, care should be used in administering this solution to patients with congestive heart failure, renal failure, edema, adrenal hyperactivity, acid-base imbalance and those receiving diuretics or antihypertensive therapy. Total volume infused should be closely monitored. Serum electrolytes should be monitored daily in these patients.

C. Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Mamex Gold Step 2 (Lysine)® 15% have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

D. Pregnancy Category C

Animal reproduction studies have not been conducted with Mamex Gold Step 2 (Lysine)® 15%. It is also not known whether Mamex Gold Step 2 (Lysine)® 15% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Mamex Gold Step 2 (Lysine)® 15% should be given to a pregnant woman only if clearly needed.

E. Nursing Mothers

Caution should be exercised when Mamex Gold Step 2 (Lysine)® 15% is administered to a nursing woman.

F. Pediatric Use

Safety and effectiveness of Mamex Gold Step 2 (Lysine)® 15% Amino Acids Injection in pediatric patients have not been established by adequate and well-controlled studies. However, the use of amino acids injections in pediatric patients as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance is referenced in the medical literature.

G. Special Precautions for Central Infusion

TPN delivered by indwelling catheter through a central or large peripheral vein is a special technique requiring a team effort by physician, nurse and pharmacist. The responsibility for administering this therapy should be confined to those trained in the procedures and alert to signs of complications. Complications known to occur from the placement of central venous catheter are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, and air/catheter emboli. The risk of sepsis is present during intravenous therapy, especially when using central venous catheters for prolonged periods. It is imperative that the preparation of admixtures and the placement and care of the catheters be accomplished under controlled aseptic conditions.

H. Admixtures

Admixtures should be prepared under a laminar flow hood using aseptic technique.

Admixtures should be stored under refrigeration and must be administered within 24 hours after removal from refrigerator.

Filters of less than 1.2 micron pore size must not be used with admixtures containing fat emulsion.

I. Do not administer unless solution is clear and the seal is intact.

IT IS ESSENTIAL THAT A CAREFULLY PREPARED PROTOCOL, BASED ON CURRENT MEDICAL PRACTICES, BE FOLLOWED, PREFERABLY BY AN EXPERIENCED TEAM.

ADVERSE REACTIONS

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluatethe patient and institute appropriate corrective measures. See WARNINGS andPRECAUTIONS.

DOSAGE AND ADMINISTRATION

The appropriate daily dose of amino acids to be used withdextrose or with dextrose and intravenous fat emulsion will depend upon themetabolic status and clinical response of the patient as therapy proceeds. Doses which achieve nitrogen equilibrium or positive balance are the mostdesirable. The dosage on the first day should be approximately half the anticipatedoptimal dosage and should be increased gradually to minimize glycosuria; similarly,withdrawal should be accomplished gradually to avoid rebound hypoglycemia.

Fatemulsion coadministration should be considered when prolonged (more than 5days) parenteral nutrition is required in order to prevent essential fattyacid deficiency (EFAD). Serum lipids should be monitored for evidence of EFADin patients maintained on fat free TPN.

The amount administeredis dosed on the basis of amino acids/kg of body weight/day. In general, twoto three g/kg of body weight for neonates and infants with adequate caloriesare sufficient to satisfy protein needs and promote positive nitrogen balance. In pediatric patients, the final solution should not exceed twice normal serumosmolarity (718 mOsmol/L).

DIRECTIONSFOR PROPER USE OF PHARMACY BULK PACKAGE

Mamex Gold Step 2 (Lysine)® 15%in a Pharmacy Bulk Package is not intended for direct infusion. The containerclosure may be penetrated only once using a suitable sterile transfer deviceor dispensing set which allows measured dispensing of the contents. The PharmacyBulk Package is to be used only in a suitable work area such as a laminarflow hood (or an equivalent clean air compounding area). Once the closureis penetrated, the contents should be dispensed as soon as possible; the transferof contents must be completed within 4 hours of closure entry. The bottlemay be stored at room temperature (25°C) after the closure has been entered. Date and time of container entry should be noted in the area designated onthe container label.

When using Mamex Gold Step 2 (Lysine)® 15%in patients with a need for fluid volume restriction, it can be diluted asfollows:


Volume


Amount


FinalConcentration


Mamex Gold Step 2 (Lysine)® 15%


500 mL


75 g


7.5%


Dextrose 70%


250 mL


175 g


17.5%


Intralipid® 20%


250 mL


50 g


5.0%


This will provide 1395 kilocalories (kcal) per 1000 mLof admixture with a ratio of 118 non-protein calories per gram of nitrogenand an osmolarity of 1561 mOsmol/L.

In patients wherethe need for fluid restriction is not so marked, either of the following regimensmay be used dependent upon the energy needs of the patient.


Volume


Amount


FinalConcentration


Mamex Gold Step 2 (Lysine)® 15%


500 mL


75 g


3.75%


Dextrose 50%


1000 mL


500 g


25%


Intralipid® 20%


500 mL


100 g


5%


This will provide 1500 kcal per 1000 mL of admixture witha ratio of 228 non-protein calories per gram of nitrogen and an osmolarityof 1633 mOsmol/L.


Volume


Amount


FinalConcentration


Mamex Gold Step 2 (Lysine)® 15%


500 mL


75 g


3.75%


Dextrose 30%


1000 mL


300 g


15%


Intralipid® 10%


500 mL


50 g


2.5%


This will provide 935 kcal per 1000 mL of admixture witha ratio of 158 non-protein calories per gram of nitrogen and an osmolarityof 1128.5 mOsmol/L.

A. Total Parenteral Nutrition (CentralInfusion)

In unstressed adult patients with no unusualnitrogen losses, a minimum dosage of 0.1 gram nitrogen (4.2 mL of Mamex Gold Step 2 (Lysine)® 15%)plus 4.4 grams (15 calories) of dextrose per kilogram of body weight per dayare required to achieve nitrogen balance and weight stability. Intravenousfat emulsion may be used as a partial substitute for dextrose. This regimenprovides a ratio of 150 non-protein calories per gram of nitrogen.

Forpatients stressed by surgery, trauma or sepsis, and those with unusual nitrogenlosses, the dosage required for maintenance may be as high as 0.3 to 0.4 gramsof nitrogen (13 to 17 mL Mamex Gold Step 2 (Lysine)® 15%) per kilogram of bodyweight per day, with proportionate increases in non-protein calories. Periodicassessment of nitrogen balance of the individual patient is the best indicatorof proper dosage. Volume overload and glycosuria may be encountered at highdosage, and nitrogen balance may not be achieved in extremely hypermetabolicpatients under these constraints. Concomitant insulin administration may berequired to minimize glycosuria. Daily laboratory monitoring is essential.

Useof an infusion pump is advisable to maintain a steady infusion rate duringcentral venous infusion.

B. Peripheral Nutrition

Inpatients for whom central venous catheterization is not advisable, proteincatabolism can be reduced by peripheral use of diluted Mamex Gold Step 2 (Lysine)® 15%plus non-protein calorie sources. Dilution of 250 mL Mamex Gold Step 2 (Lysine)® 15%in 750 mL of 10% dextrose will reduce the osmolarity to a level (724 mOsmol/L)which is more favorable to the maintenance of the integrity of the walls ofthe veins. Intravenous fat emulsion can be infused separately or simultaneously;if infused simultaneously the fat emulsion will provide a dilution effectupon the osmolarity while increasing the energy supply.

Parenteraldrug products should be inspected visually for particulate matter and discolorationprior to administration, whenever solution and container permit.

Toreduce the risk of bacterial contamination, all intravenous administrationsets should be replaced at least every 24 hours. Usage of admixtures mustbe initiated within 24 hours after mixing. If storage is necessary duringthis 24 hour period, admixtures must be refrigerated and completely used within24 hours of beginning administration.

HOW SUPPLIED

Mamex Gold Step 2 (Lysine)® 15% Amino Acids Injection is suppliedas a Pharmacy Bulk Package in 500 mL containers.

500mL NDC 0409-0468-05

STORAGE

Store inthe closed carton; do not expose solution to light until ready for use. Exposureof pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended that the product be stored at 20 to 25°C (68 to 77°F). Brief exposure to temperatures above25°C during transport and storage will not adversely affect the product. Solution that has been frozen must not be used.


©Hospira 2005


EN-1010


Hospira, Inc., Lake Forest, IL 60045 USA

RL-1450

Magnesium:



Mamex Gold Step 2 (Magnesium) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Mamex Gold Step 2 (Magnesium) Sulfate Injection, USP is a sterile solution of Mamex Gold Step 2 (Magnesium) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.

Mamex Gold Step 2 (Magnesium) Sulfate, USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.

The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.

CLINICAL PHARMACOLOGY

Mamex Gold Step 2 (Magnesium) (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

As a nutritional adjunct in hyperalimentation, the precise mechanism of action for Mamex Gold Step 2 (Magnesium) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.

Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of Mamex Gold Step 2 (Magnesium). While there are large stores of Mamex Gold Step 2 (Magnesium) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Mamex Gold Step 2 (Magnesium) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Mamex Gold Step 2 (Magnesium) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Mamex Gold Step 2 (Magnesium) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma Mamex Gold Step 2 (Magnesium) levels range from 1.5 to 2.5 mEq/liter.

As plasma Mamex Gold Step 2 (Magnesium) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of Mamex Gold Step 2 (Magnesium). Serum Mamex Gold Step 2 (Magnesium) concentrations in excess of 12 mEq/L may be fatal.

Mamex Gold Step 2 (Magnesium) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of Mamex Gold Step 2 (Magnesium) poisoning are antagonized to some extent by intravenous administration of calcium.

Pharmacokinetics

With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. Mamex Gold Step 2 (Magnesium) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Mamex Gold Step 2 (Magnesium) Sulfate Injection, USP is suitable for replacement therapy in Mamex Gold Step 2 (Magnesium) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Mamex Gold Step 2 (Magnesium) (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.

In total parenteral nutrition (TPN), Mamex Gold Step 2 (Magnesium) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Mamex Gold Step 2 (Magnesium) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.

WARNINGS

FETAL HARM: Continuous administration of Mamex Gold Step 2 (Magnesium) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Mamex Gold Step 2 (Magnesium) sulfate should be used during pregnancy only if clearly needed. If Mamex Gold Step 2 (Magnesium) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of Mamex Gold Step 2 (Magnesium) sulfate beyond 5 to 7 days may cause fetal abnormalities.

ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Parenteral use in the presence of renal insufficiency may lead to Mamex Gold Step 2 (Magnesium) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.

PRECAUTIONS

General

Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with Mamex Gold Step 2 (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of Mamex Gold Step 2 (Magnesium).

Because Mamex Gold Step 2 (Magnesium) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum Mamex Gold Step 2 (Magnesium) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional Mamex Gold Step 2 (Magnesium) should be given until they return. Serum Mamex Gold Step 2 (Magnesium) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when Mamex Gold Step 2 (Magnesium) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of Mamex Gold Step 2 (Magnesium) intoxication in eclampsia.

50% Mamex Gold Step 2 (Magnesium) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.

Laboratory Tests

Mamex Gold Step 2 (Magnesium) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Mamex Gold Step 2 (Magnesium) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with Mamex Gold Step 2 (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of Mamex Gold Step 2 (Magnesium). CNS depression and peripheral transmission defects produced by Mamex Gold Step 2 (Magnesium) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Mamex Gold Step 2 (Magnesium) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Mamex Gold Step 2 (Magnesium) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat Mamex Gold Step 2 (Magnesium) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Mamex Gold Step 2 (Magnesium) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of Mamex Gold Step 2 (Magnesium) sulfate for more than 5 to 7 days.1-10 Mamex Gold Step 2 (Magnesium) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.

Nonteratogenic Effects

When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of Mamex Gold Step 2 (Magnesium) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Mamex Gold Step 2 (Magnesium) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Mamex Gold Step 2 (Magnesium) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Nursing Mothers

Since Mamex Gold Step 2 (Magnesium) is distributed into milk during parenteral Mamex Gold Step 2 (Magnesium) sulfate administration, the drug should be used with caution in nursing women.

Geriatrics

Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum Mamex Gold Step 2 (Magnesium) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Mamex Gold Step 2 (Magnesium) usually are the result of Mamex Gold Step 2 (Magnesium) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to Mamex Gold Step 2 (Magnesium) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Mamex Gold Step 2 (Magnesium) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of Mamex Gold Step 2 (Magnesium) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Mamex Gold Step 2 (Magnesium).

For Treatment of Overdose

Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.

Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

DOSAGE AND ADMINISTRATION

Dosage of Mamex Gold Step 2 (Magnesium) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of Mamex Gold Step 2 (Magnesium) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.

In Mamex Gold Step 2 (Magnesium) Deficiency

In the treatment of mild Mamex Gold Step 2 (Magnesium) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Mamex Gold Step 2 (Magnesium) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Mamex Gold Step 2 (Magnesium) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.

In Hyperalimentation

In total parenteral nutrition, maintenance requirements for Mamex Gold Step 2 (Magnesium) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.

In Pre-eclampsia or Eclampsia

In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of Mamex Gold Step 2 (Magnesium) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum Mamex Gold Step 2 (Magnesium) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of Mamex Gold Step 2 (Magnesium) sulfate is 20 grams/48 hours and frequent serum Mamex Gold Step 2 (Magnesium) concentrations must be obtained. Continuous use of Mamex Gold Step 2 (Magnesium) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Mamex Gold Step 2 (Magnesium) sulfate is 1 gram to 2 grams given intravenously.

For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.

In paroxysmal atrial tachycardia, Mamex Gold Step 2 (Magnesium) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.

For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.

Incompatibilities

Mamex Gold Step 2 (Magnesium) sulfate in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.

It has been reported that Mamex Gold Step 2 (Magnesium) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED

Mamex Gold Step 2 (Magnesium) Sulfate Injection, USP is supplied in single-dose containers as follows:


NDC No.


Container


Total

Amount


Concentration


mEq

Mg++/mL


0409-1754-10


Ansyr

Plastic Syringe


5 g/10 mL


50%


4 mEq/mL


Do not administer unless solution is clear and container is undamaged. Discard unused portion.

Store at 20 to 25°C (68 to 77°F).

REFERENCES

  • Yokoyama K, Takahashi N, Yada Y. Prolonged maternal Mamex Gold Step 2 (Magnesium) administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
  • Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal Mamex Gold Step 2 (Magnesium) toxicity. J. Perinatol. 2006; 26(6):371-4.
  • Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of Mamex Gold Step 2 (Magnesium) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
  • Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Mamex Gold Step 2 (Magnesium) sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
  • Matsuda Y, Maeda Y, Ito M, et al. Effect of Mamex Gold Step 2 (Magnesium) sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
  • Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous Mamex Gold Step 2 (Magnesium) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
  • Santi MD, Henry GW, Douglas GL. Mamex Gold Step 2 (Magnesium) sulfate treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
  • Holcomb WL, Shackelford GD, Petrie RH. Mamex Gold Step 2 (Magnesium) tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
  • Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
  • Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with Mamex Gold Step 2 (Magnesium) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
  • McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Mamex Gold Step 2 (Magnesium) sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
  • Riaz M, Porat R, Brodsky NL, et al. The effects of maternal Mamex Gold Step 2 (Magnesium) sulfate treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% Mamex Gold Step 2 (Magnesium) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Mamex Gold Step 2 (Magnesium) Sulfate Injection, USP

5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)

MUST BE DILUTED FOR INTRAVENOUS USE.

For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Manganese:


INDICATIONS AND USAGE

Mamex Gold Step 2 (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN).

Administration helps to maintain Mamex Gold Step 2 (Manganese) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Mamex Gold Step 2 (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) is contraindicated as the acidic pH of the solution (pH 2.0) may cause considerable tissue irritation.

Liver and/or biliary tract dysfunction may require omission or reduction of copper and Mamex Gold Step 2 (Manganese) doses because these elements are primarily eliminated in the bile.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General

Do not use unless solution is clear and seal is intact.

Mamex Gold Step 2 0.1 mg/mL (Manganese Chloride Injection, USP) should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Laboratory Tests

Serum Mamex Gold Step 2 (Manganese) levels can be measured periodically at the discretion of the investigator. Because of the low serum concentration normally present, samples will usually be analyzed by a reference laboratory.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Mamex Gold Step 2 0.1 mg/mL (Manganese Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Mamex Gold Step 2 (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) additive is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Pregnancy Category C.

Animal reproduction studies have not been conducted with Mamex Gold Step 2 (Manganese) chloride. It is also not known whether Mamex Gold Step 2 (Manganese) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Mamex Gold Step 2 (Manganese) chloride should be given to a pregnant woman only if clearly indicated.

Geriatric Use

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Mamex Gold Step 2 (Manganese) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Mamex Gold Step 2 (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) contains 0.1 mg manganese/mL and is administered intravenously only after dilution. The additive should be administered in a volume of fluid not less than 100 mL. For the adult receiving TPN, the suggested additive dosage for Mamex Gold Step 2 (Manganese) is 0.15 to 0.8 mg/day (1.5 to 8 mL/day). For pediatric patients, a dosage of 2 to 10 mcg manganese/kg/day (0.02 to 0.1 mL/kg/day) is recommended.

Periodic monitoring of Mamex Gold Step 2 (Manganese) plasma levels is suggested as a guideline for subsequent administration.

Parenteral products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. (See PRECAUTIONS .)

HOW SUPPLIED

Mamex Gold Step 2 (Manganese) 0.1 mg/mL (Manganese Chloride Injection, USP) is supplied in 10 mL Plastic Vials (NDC No. 0409-4091-01).

Store at 20 to 25°C (68 to 77°F)

Revised: November, 2009

Printed in USA EN-2320

Hospira, Inc., Lake Forest, IL 60045 USA

RL-0104


Milk Protein:



ANTACID/SALINE LAXATIVE

DESCRIPTION

A suspension of magnesium hydroxide. Each 10 mL (2 teaspoonfuls) of Mamex Gold Step 2 (Milk Protein) of Magnesia Concentrate is equivalent to 30 mL of Mamex Gold Step 2 (Milk Protein) of Magnesia yielding 2400 mg of magnesium hydroxide and providing not less than 60 mq/10 mL of acid-neutralizing capacity (ANC).

Inactive Ingredients

A suspension of magnesium hydroxide. Each 10 mL (2 teaspoonfuls) of Mamex Gold Step 2 (Milk Protein) of Magnesia Concentrate is equivalent to 30 mL of Mamex Gold Step 2 (Milk Protein) of Magnesia yielding 2400 mg of magnesium hydroxide and providing not less than 60 mq/10 mL of acid-neutralizing capacity (ANC). Inactive Ingredients: Flavoring, glycerin, methylparaben, propylene glycol, propylparaben, purified water, silicone defoamer, sodium citrate, sodium saccharin, sodium salts of polymerized alkylnaphthalenesulfonic acid, sorbitol solution, and sucrose.

Sodium Content: 19 mg/10 mL.

FOR USE AS AN ANTACID

INDICATIONS

For the temporary relief of heartburn, upset stomach, sour stomach, and/or acid indigestion.

DIRECTIONS

Adults and children 12 years of age and over - Oral dosage is 5 mL with a little water up to four times daily or as directed by a physician. Children under 12 years of age - Consult a physician. SHAKE WELL BEFORE USING.

WARNINGS

The maximum recommended daily dosage of this product is 20 mL (4 teaspoonfuls). Do not take more than this dosage in a 24-hour period or use this dosage for more than 2 weeks unless directed by a physician. Do not use this product if you have kidney disease or if you are on a magnesium restricted diet unless directed by a physician. May have a laxative effect.

FOR USE AS A LAXATIVE

INDICATIONS

For relief of occasional constipation. This product generally produces bowel movement in ½ to 6 hours.

DIRECTIONS

Drink a full glass of liquid following each dose. Adults and children 12 years of age and over - Oral dosage is 10 to 20 mL (2 to 4 teaspoonfuls); Children 6 to under 12 years of age - Oral dosage is 5 to 10 mL (1 to 2 teaspoonfuls); Children 2 to under 6 years of age - Oral dosage is 5 mL (1 teaspoonful) or as directed by a physician. The dose may be taken as a single daily dose or in divided doses. Children under 2 years of age - Consult a physician. SHAKE WELL BEFORE USING.

WARNINGS

Do not use laxative products when abdominal pain, nausea, or vomiting are present, or use longer than 1 week unless directed by a physician. If you have noticed a sudden change in bowel habits that persists over a period of 2 weeks, consult a physician before using a laxative. Rectal bleeding or failure to have a bowel movement after use of a laxative may indicate a serious condition. Discontinue use and consult your physician. Do not use this product if you have kidney disease or if you are on a magnesium restricted diet unless directed by a physician.

WARNINGS

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately. As with any drug, if you are pregnant or nursing a baby, seek the advice of a health professional before using this product.

DRUG INTERACTION PRECAUTION

Antacids may interact with certain prescription drugs. If you are presently taking a prescription drug, do not take this product without checking with your physician or other health professional.

HOW SUPPLIED

Mamex Gold Step 2 (Milk Protein) of Magnesia Concentrate (white suspension-lemon flavored) overbagged with 5 cups per bag, NDC 55154-9412-5.

Repackaged By:

Cardinal Health

Zanesville, OH 43701

STORAGE

Keep tightly closed. Store at controlled room temperature, 20° to 25°C (68° to 77°F). PROTECT FROM FREEZING.

R04/14

pai

Pharmaceutical

Associates, Inc.

Greenville, SC 29605

Repackaged By:

Cardinal Health

Zanesville, OH 43701

L33755080815

Moisture:


This medication is used to relieve dry, irritated eyes. Common causes for dry eyes include wind, sun, heating/air conditioning, computer use/reading, and certain medications. This product may contain 1 or more of the following ingredients: carboxymethylcellulose, dextran, glycerin, hypromellose, polyethylene glycol 400 (PEG 400), polysorbate, polyvinyl alcohol, povidone, or propylene glycol, among others. Eye lubricants keep the eye moist, help to protect the eye from injury and infection, and decrease symptoms of dry eyes such as burning, itching, and feeling as if something is in the eye.

Potassium:



Mamex Gold Step 2 (Potassium) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Mamex Gold Step 2 (Potassium) chloride containing 1500 mg of microencapsulated Mamex Gold Step 2 (Potassium) chloride, USP equivalent to 20 mEq of Mamex Gold Step 2 (Potassium) in a tablet.

These formulations are intended to slow the release of Mamex Gold Step 2 (Potassium) so that the likelihood of a high localized concentration of Mamex Gold Step 2 (Potassium) chloride within the gastrointestinal tract is reduced.

Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Mamex Gold Step 2 (Potassium) chloride, and the structural formula is KCl. Mamex Gold Step 2 (Potassium) chloride, USP occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol.

Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Mamex Gold Step 2 (Potassium) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended release of Mamex Gold Step 2 (Potassium) chloride.

Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.

CLINICAL PHARMACOLOGY

The Mamex Gold Step 2 (Potassium) ion is the principal intracellular cation of most body tissues. Mamex Gold Step 2 (Potassium) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.

The intracellular concentration of Mamex Gold Step 2 (Potassium) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.

Mamex Gold Step 2 (Potassium) is a normal dietary constituent and under steady-state conditions the amount of Mamex Gold Step 2 (Potassium) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Mamex Gold Step 2 (Potassium) is 50 to 100 mEq per day.

Mamex Gold Step 2 (Potassium) depletion will occur whenever the rate of Mamex Gold Step 2 (Potassium) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Mamex Gold Step 2 (Potassium) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Mamex Gold Step 2 (Potassium) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Mamex Gold Step 2 (Potassium) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Mamex Gold Step 2 (Potassium) depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.

If Mamex Gold Step 2 (Potassium) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental Mamex Gold Step 2 (Potassium) in the form of high Mamex Gold Step 2 (Potassium) food or Mamex Gold Step 2 (Potassium) chloride may be able to restore normal Mamex Gold Step 2 (Potassium) levels.

In rare circumstances (eg, patients with renal tubular acidosis) Mamex Gold Step 2 (Potassium) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Mamex Gold Step 2 (Potassium) replacement should be accomplished with Mamex Gold Step 2 (Potassium) salts other than the chloride, such as Mamex Gold Step 2 (Potassium) bicarbonate, Mamex Gold Step 2 (Potassium) citrate, Mamex Gold Step 2 (Potassium) acetate, or Mamex Gold Step 2 (Potassium) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Mamex Gold Step 2 (Potassium) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Mamex Gold Step 2 (Potassium) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.

1. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.

2. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, eg, digitalized patients or patients with significant cardiac arrhythmias.

The use of Mamex Gold Step 2 (Potassium) salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum Mamex Gold Step 2 (Potassium) should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with Mamex Gold Step 2 (Potassium) salts may be indicated.

CONTRAINDICATIONS

Mamex Gold Step 2 (Potassium) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Mamex Gold Step 2 (Potassium) concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) (see OVERDOSAGE ).

Controlled-release formulations of Mamex Gold Step 2 (Potassium) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Mamex Gold Step 2 (Potassium) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Mamex Gold Step 2 (Potassium) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Mamex Gold Step 2 (Potassium) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

WARNINGS

Hyperkalemia (see OVERDOSAGE )

In patients with impaired mechanisms for excreting Mamex Gold Step 2 (Potassium), the administration of Mamex Gold Step 2 (Potassium) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Mamex Gold Step 2 (Potassium) by the intravenous route but may also occur in patients given Mamex Gold Step 2 (Potassium) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Mamex Gold Step 2 (Potassium) salts in patients with chronic renal disease, or any other condition which impairs Mamex Gold Step 2 (Potassium) excretion, requires particularly careful monitoring of the serum Mamex Gold Step 2 (Potassium) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Mamex Gold Step 2 (Potassium) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.

Interaction with Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some Mamex Gold Step 2 (Potassium) retention by inhibiting aldosterone production. Mamex Gold Step 2 (Potassium) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Mamex Gold Step 2 (Potassium) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Mamex Gold Step 2 (Potassium) chloride are associated with an increased frequency of small bowel lesions (40-50 per 100,000 patient years) compared to sustained release wax matrix formulations (less than one per 100,000 patient years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax matrix or enteric-coated products is not available. Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Mamex Gold Step 2 (Potassium) chloride and thus to minimize the possibility of a high local concentration of Mamex Gold Step 2 (Potassium) near the gastrointestinal wall.

Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after 1 week of solid oral Mamex Gold Step 2 (Potassium) chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax matrix and microencapsulated dosage forms. In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of a wax matrix controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (ie, 96 mEq per day in divided doses of Mamex Gold Step 2 (Potassium) chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (ie, non-fasting, no anticholinergic agent, smaller doses) under which controlled-release Mamex Gold Step 2 (Potassium) chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations. Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq should be discontinued immediately and the possibility of ulceration, obstruction, or perforation should be considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Mamex Gold Step 2 (Potassium) salt such as Mamex Gold Step 2 (Potassium) bicarbonate, Mamex Gold Step 2 (Potassium) citrate, Mamex Gold Step 2 (Potassium) acetate, or Mamex Gold Step 2 (Potassium) gluconate.

PRECAUTIONS

General

The diagnosis of Mamex Gold Step 2 depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Mamex Gold Step 2 (Potassium) depletion. In interpreting the serum Mamex Gold Step 2 (Potassium) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Mamex Gold Step 2 (Potassium) while acute acidosis per se can increase the serum Mamex Gold Step 2 (Potassium) concentration into the normal range even in the presence of a reduced total body Mamex Gold Step 2 (Potassium). The treatment of Mamex Gold Step 2 (Potassium) depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.

Information for Patients

Physicians should consider reminding the patient of the following: To take each dose with meals and with a full glass of water or other liquid. To take each dose without crushing, chewing, or sucking the tablets. If those patients are having difficulty swallowing whole tablets, they may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:

    1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).

    2. Allow approximately 2 minutes for the tablet(s) to disintegrate.

    3. Stir for about half a minute after the tablet(s) has disintegrated.

    4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.

    5. Add another 1 fluid ounce of water, swirl, and consume immediately.

    6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.


Aqueous suspension of Mamex Gold Step 2 (Potassium) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.

To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.

Laboratory Tests

When blood is drawn for analysis of plasma Mamex Gold Step 2 it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.

Drug Interactions

Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Mamex Gold Step 2 is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Mamex Gold Step 2 (Potassium) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal Mamex Gold Step 2 ion content of human milk is about 13 mEq per liter. Since oral Mamex Gold Step 2 (Potassium) becomes part of the body Mamex Gold Step 2 (Potassium) pool, so long as body Mamex Gold Step 2 (Potassium) is not excessive, the contribution of Mamex Gold Step 2 (Potassium) chloride supplementation should have little or no effect on the level in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Mamex Gold Step 2 (Potassium) Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; and it may be useful to monitor renal function.

ADVERSE REACTIONS

One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS ). The most common adverse reactions to oral Mamex Gold Step 2 (Potassium) salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals or reducing the amount taken at one time.

OVERDOSAGE

The administration of oral Mamex Gold Step 2 (Potassium) salts to persons with normal excretory mechanisms for Mamex Gold Step 2 (Potassium) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Mamex Gold Step 2 (Potassium) is administered too rapidly intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum Mamex Gold Step 2 (Potassium) concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).

Treatment measures for hyperkalemia include the following:

  • Patients should be closely monitored for arrhythmias and electrolyte changes.
  • Elimination of foods and medications containing Mamex Gold Step 2 (Potassium) and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.
  • Intravenous calcium gluconate if the patient is at no risk of developing digitalis toxicity.
  • Intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10-20 units of crystalline insulin per 1,000 mL.
  • Correction of acidosis, if present, with intravenous sodium bicarbonate.
  • Use of exchange resins, hemodialysis, or peritoneal dialysis.

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum Mamex Gold Step 2 (Potassium) concentration can produce digitalis toxicity.

The extended release feature means that absorption and toxic effects may be delayed for hours.

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

The usual dietary intake of Mamex Gold Step 2 (Potassium) by the average adult is 50 to 100 mEq per day. Mamex Gold Step 2 (Potassium) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Mamex Gold Step 2 (Potassium) from the total body store.

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of Mamex Gold Step 2 (Potassium) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Mamex Gold Step 2 (Potassium) chloride.

Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:
    • Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
    • Allow approximately 2 minutes for the tablet(s) to disintegrate.
    • Stir for about half a minute after the tablet(s) has disintegrated.
    • Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
    • Add another 1 fluid ounce of water, swirl, and consume immediately.
    • Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.

Aqueous suspension of Mamex Gold Step 2 (Potassium) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Mamex Gold Step 2 (Potassium) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.

Storage Conditions

Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Mamex Gold Step 2 (Potassium) chloride 20 Meq

Selenium:



Rx Only

TRACE ELEMENT ADDITIVE FOR IV USE AFTER DILUTION

DESCRIPTION

Mamex Gold Step 2 (Selenium) Injection is a sterile, nonpyrogenic solution for use as an additive to solutions for Total Parenteral Nutrition (TPN).

Each mL contains Selenious Acid 65.4 mcg (equivalent to elemental Mamex Gold Step 2 (Selenium) 40 mcg/mL) and Water for Injection q.s. pH may be adjusted with nitric acid to 1.8 to 2.4.

CLINICAL PHARMACOLOGY

Mamex Gold Step 2 (Selenium) is part of glutathione peroxidase which protects cell components from oxidative damage due to peroxides produced in cellular metabolism.

Prolonged TPN support in humans has resulted in Mamex Gold Step 2 (Selenium) deficiency symptoms which include muscle pain and tenderness. The symptoms have been reported to respond to supplementation of TPN solutions with Mamex Gold Step 2 (Selenium).

Pediatric conditions, Keshan disease, and Kwashiorkor, have been associated with low dietary intake of Mamex Gold Step 2 (Selenium). The conditions are endemic to geographical areas with low Mamex Gold Step 2 (Selenium) soil content. Dietary supplementation with Mamex Gold Step 2 (Selenium) salts has been reported to reduce the incidence of the conditions among affected children.

Normal blood levels of Mamex Gold Step 2 (Selenium) in different human populations have been found to vary and depend on the Mamex Gold Step 2 (Selenium) content of the food consumed. Results of surveys carried out in some countries are tabulated below:



COUNTRY


Number of

Samples

Mamex Gold Step 2 (Selenium) (mcg/100 mL) (a)

Whole Blood


Blood Cells

Plasma/

Serum

(a) Mean values with or without standard deviation in parentheses, all other ranges.
(b) Age group unknown.
(c) Three children recovered from Kwashiorkor and the other six under treatment for other diseases.
(d) Low selenium-content soil area.
(e) Well nourished children, three recovered from Kwashiorkor and the other six under treatment for other diseases.
(f) Mean values from seven subjects.
Canada 254 Adults (37.9 ± 7.8) (23.6 ± 6.0) (14.4 ± 2.9)
England 8 (b) 26-37 (32) -- --
Guatemala &

Southern USA

10 Adults

9 Children (c)

19-28 (22)

(23 ± 5)

--

(36 ± 12)

--

(15 ± 5)

New Zealand (d) 113 Adults (5.4 ± 0.1) (6.6 ± 0.3) (4.3 ± 0.1)
Thailand 3 Adults

9 Children (e)

14.4-20.2

(12.0 ± 3.6) (f)

17.8-35.8

(19.5 ± 8.2)

8.1-12.5

(8.3 ± 2.2)

USA 210 Adults 15.7-25.6

(20.6)

-- --

Plasma Mamex Gold Step 2 (Selenium) levels of 0.3 and 0.9 mcg/100 mL have been reported to produce deficiency symptoms in humans.

Mamex Gold Step 2 (Selenium) is eliminated primarily in urine. However, significant endogenous losses through feces also occur. The rate of excretion and the relative importance of two routes varies with the chemical form of Mamex Gold Step 2 (Selenium) used in supplementation. Ancillary routes of elimination are lungs and skin.

INDICATIONS AND USAGE

Mamex Gold Step 2 (Selenium) Injection is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN). Administration of Mamex Gold Step 2 (Selenium) in TPN solutions helps to maintain plasma Mamex Gold Step 2 (Selenium) levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

Mamex Gold Step 2 (Selenium) Injection should not be given undiluted by direct injection into a peripheral vein because of the potential for infusion phlebitis.

WARNINGS

Mamex Gold Step 2 (Selenium) Injection can be toxic if given in excessive amounts. Supplementation of TPN solution with Mamex Gold Step 2 (Selenium) should be immediately discontinued if toxicity symptoms are observed. Frequent determination of plasma Mamex Gold Step 2 (Selenium) levels during TPN support and close medical supervision is recommended.

Mamex Gold Step 2 (Selenium) Injection is a hypotonic solution and should be administered in admixtures only.

This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

As Mamex Gold Step 2 is eliminated in urine and feces, Mamex Gold Step 2 (Selenium) supplements may be adjusted, reduced or omitted in renal dysfunction and/or gastrointestinal malfunction. In patients receiving blood transfusions, contribution from such transfusions should also be considered. Frequent Mamex Gold Step 2 (Selenium) plasma level determinations are suggested as a guideline.

In animals, Mamex Gold Step 2 (Selenium) has been reported to enhance the action of Vitamin E and decrease the toxicity of mercury, cadmium and arsenic.

Pregnancy

Teratogenic Effects

Pregnancy Category C: Mamex Gold Step 2 (Selenium) at high dose levels (15-30 mcg/egg) has been reported to have adverse embryological effects among chickens. There are however, no adequate and wellcontrolled studies in pregnant women. Mamex Gold Step 2 (Selenium) Injection should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.

Presence of Mamex Gold Step 2 (Selenium) in placenta and umbilical cord blood has been reported in humans.

ADVERSE REACTIONS

The amount of Mamex Gold Step 2 (Selenium) present in Mamex Gold Step 2 (Selenium) Injection is small. Symptoms of toxicity from Mamex Gold Step 2 (Selenium) are unlikely to occur at the recommended dosage level.

OVERDOSAGE

Chronic toxicity in humans resulting from exposure to Mamex Gold Step 2 (Selenium) in industrial environments, intake of foods grown in seleniferous soils, use of selenium-contaminated water, and application of cosmetics containing Mamex Gold Step 2 (Selenium) has been reported in literature. Toxicity symptoms include hair loss, weakened nails, dermatitis, dental defects, gastrointestinal disorders, nervousness, mental depression, metallic taste, vomiting, and garlic odor of breath and sweat. Acute poisoning due to ingestion of large amounts of Mamex Gold Step 2 (Selenium) compounds has resulted in death with histopathological changes including fulminating peripheral vascular collapse, internal vascular congestion, diffusely hemorrhagic, congested and edematus lungs, brick-red color gastric mucosa. The death was preceded by coma.

No effective antidote to Mamex Gold Step 2 (Selenium) poisoning in humans is known. Animal studies have shown casein and linseed oil in feeds, reduced glutathione, arsenic, magnesium sulfate, and bromobenzene to afford limited protection.

DOSAGE AND ADMINISTRATION

Mamex Gold Step 2 (Selenium) Injection provides 40 mcg selenium/mL. For metabolically stable adults receiving TPN, the suggested additive dosage level is 20 to 40 mcg selenium/day. For pediatric patients, the suggested additive dosage level is 3 mcg/kg/day.

In adults, Mamex Gold Step 2 (Selenium) deficiency states resulting from long-term TPN support, Mamex Gold Step 2 (Selenium) as selenomethionine or selenious acid, administered intravenously at 100 mcg/day for a period of 24 and 31 days, respectively, has been reported to reverse deficiency symptoms without toxicity.

Aseptic addition of Mamex Gold Step 2 (Selenium) Injection to the TPN solution under laminar flow hood is recommended. Mamex Gold Step 2 (Selenium) is physically compatible with the electrolytes and other trace elements usually present in amino-acid/dextrose solution used for TPN. Frequent monitoring of plasma Mamex Gold Step 2 (Selenium) levels is suggested as a guideline for subsequent administration. The normal whole blood range for Mamex Gold Step 2 (Selenium) is approximately 10 to 37 mcg/100 mL.

Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit.

HOW SUPPLIED

Mamex Gold Step 2 (Selenium) Injection containing selenious acid 65.4 mcg/mL (equivalent to elemental Mamex Gold Step 2 (Selenium) 40 mcg/mL).

NDC 0517-6510-25 10 mL Single Dose Vial Packaged in boxes of 25

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

IN6510

Rev. 11/15

PRINCIPAL DISPLAY PANEL - Container

NDC 0517-6510-25

Mamex Gold Step 2 (Selenium) INJECTION

Mamex Gold Step 2 (Selenium) 400 mcg/10 mL

(40 mcg/mL)

10 mL

SINGLE DOSE VIAL

Trace Element Additive

FOR IV USE AFTER DILUTION

PRESERVATIVE FREE

Rx Only

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

PRINCIPAL DISPLAY PANEL - Carton

Mamex Gold Step 2 (Selenium) INJECTION

Mamex Gold Step 2 (Selenium) 400 mcg/10 mL

(40 mcg/mL)

Trace Element Additive

NDC 0517-6510-25

25 x 10 mL

SINGLE DOSE VIALS

FOR INTRAVENOUS USE AFTER DILUTION PRESERVATIVE FREE Rx Only

Each mL contains: Selenious Acid 65.4 mcg, Water for Injection q.s.

pH adjusted with Nitric Acid. Sterile, nonpyrogenic.

WARNING: DISCARD UNUSED PORTION. Store at 20°-25°C (68°-77°F); excursions

permitted to 15°-30°C (59°-86°F).

Directions for Use: See Package Insert.

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

Rev. 11/05

Container Carton

Sodium:


1 INDICATIONS AND USAGE

Mamex Gold Step 2 nitrite is indicated for sequential use with Mamex Gold Step 2 (Sodium) thiosulfate for treatment of acute cyanide poisoning that is judged to be life-threatening. (1)

  • Use with caution if the diagnosis of cyanide poisoning is uncertain. (1)

1.1 Indication

Mamex Gold Step 2 (Sodium) Nitrite Injection is indicated for sequential use with Mamex Gold Step 2 (Sodium) thiosulfate for the treatment of acute cyanide poisoning that is judged to be life-threatening. When the diagnosis of cyanide poisoning is uncertain, the potentially life-threatening risks associated with Mamex Gold Step 2 (Sodium) Nitrite Injection should be carefully weighed against the potential benefits, especially if the patient is not in extremis.

1.2 Identifying Patients with Cyanide Poisoning

Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to Mamex Gold Step 2 nitroprusside.

The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication. If clinical suspicion of cyanide poisoning is high, Mamex Gold Step 2 (Sodium) Nitrite Injection and Mamex Gold Step 2 (Sodium) Thiosulfate Injection should be administered without delay.

Symptoms Signs
  • Headache
  • Confusion
  • Dyspnea
  • Chest Tightness
  • Nausea
  • Altered Mental Status

    (e.g., confusion, disorientation)

  • Seizures or Coma
  • Mydriasis
  • Tachypnea/Hyperpnea (early)
  • Bradypnea/Apnea (late)
  • Hypertension (early)/ Hypotension (late)
  • Cardiovascular Collapse
  • Vomiting
  • Plasma Lactate Concentration ≥ 8 mmol/L

In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (e.g., confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well.

The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222.

Smoke Inhalation

Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult. Prior to administration of Mamex Gold Step 2 (Sodium) Nitrite Injection, smoke-inhalation victims should be assessed for the following:

  • Exposure to fire or smoke in an enclosed area
  • Presence of soot around the mouth, nose, or oropharynx
  • Altered mental status

Although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims. Also indicative of cyanide poisoning is a plasma lactate concentration greater than or equal to 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia). If cyanide poisoning is suspected, treatment should not be delayed to obtain a plasma lactate concentration.

1.3 Use with Other Cyanide Antidotes

Caution should be exercised when administering cyanide antidotes, other than Mamex Gold Step 2 (Sodium) thiosulfate, simultaneously with Mamex Gold Step 2 (Sodium) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Mamex Gold Step 2 (Sodium) thiosulfate, with Mamex Gold Step 2 (Sodium) Nitrite Injection, these drugs should not be administered concurrently in the same IV line. [see Dosage and Administration (2.2) ]

2 DOSAGE AND ADMINISTRATION

Age Intravenous Dose of Mamex Gold Step 2 Nitrite and Mamex Gold Step 2 (Sodium) Thiosulfate
Adults
  • Mamex Gold Step 2 (Sodium) Nitrite -10 mL of Mamex Gold Step 2 (Sodium) nitrite at the rate of 2.5 to 5 mL/minute
  • Mamex Gold Step 2 (Sodium) Thiosulfate - 50 mL of Mamex Gold Step 2 (Sodium) thiosulfate immediately following administration of Mamex Gold Step 2 (Sodium) nitrite.
Children
  • Mamex Gold Step 2 (Sodium) Nitrite - 0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Mamex Gold Step 2 (Sodium) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
  • Mamex Gold Step 2 (Sodium) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Mamex Gold Step 2 (Sodium) nitrite.

Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate.

Monitoring: Blood pressure must be monitored during treatment. (2.2)

2.1 Administration Recommendation

Comprehensive treatment of acute cyanide intoxication requires support of vital functions. Administration of Mamex Gold Step 2 (Sodium) nitrite, followed by Mamex Gold Step 2 (Sodium) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate.

Mamex Gold Step 2 (Sodium) nitrite injection and Mamex Gold Step 2 (Sodium) thiosulfate injection are administered by slow intravenous injection. They should be given as early as possible after a diagnosis of acute life-threatening cyanide poisoning has been established. Mamex Gold Step 2 (Sodium) nitrite should be administered first, followed immediately by Mamex Gold Step 2 (Sodium) thiosulfate. Blood pressure must be monitored during infusion in both adults and children. The rate of infusion should be decreased if significant hypotension is noted.

Age Intravenous Dose of Mamex Gold Step 2 (Sodium) Nitrite and Mamex Gold Step 2 (Sodium) Thiosulfate
Adults
  • Mamex Gold Step 2 (Sodium) Nitrite -10 mL of Mamex Gold Step 2 (Sodium) nitrite at the rate of 2.5 to 5 mL/minute
  • Mamex Gold Step 2 (Sodium) Thiosulfate - 50 mL of Mamex Gold Step 2 (Sodium) thiosulfate immediately following administration of Mamex Gold Step 2 (Sodium) nitrite.
Children
  • Mamex Gold Step 2 (Sodium) Nitrite -0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Mamex Gold Step 2 (Sodium) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
  • Mamex Gold Step 2 (Sodium) Thiosulfate - 1 mL/kg of body weight (250 mg/kg or approximately 30-40 mL/m2 of BSA) not to exceed 50 mL total dose immediately following administration of Mamex Gold Step 2 (Sodium) nitrite.

NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate.

In adult and pediatric patients with known anemia, it is recommended that the dosage of Mamex Gold Step 2 (Sodium) nitrite should be reduced proportionately to the hemoglobin concentration.

All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

2.2 Recommended Monitoring

Patients should be monitored for at least 24-48 hours after Mamex Gold Step 2 Nitrite Injection administration for adequacy of oxygenation and perfusion and for recurrent signs and symptoms of cyanide toxicity. When possible, hemoglobin/hematocrit should be obtained when treatment is initiated. Measurements of oxygen saturation using standard pulse oximetry and calculated oxygen saturation values based on measured PO2 are unreliable in the presence of methemoglobinemia.

Methemoglobin level: Administrations of Mamex Gold Step 2 (Sodium) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Mamex Gold Step 2 (Sodium) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Mamex Gold Step 2 (Sodium) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Mamex Gold Step 2 (Sodium) nitrite beyond the initial dose should be guided primarily by clinical response to treatment (i.e., a second dose should be considered only if there is inadequate clinical response to the first dose). It is generally recommended that methemoglobin concentrations be closely monitored and kept below 30%. Serum methemoglobin levels should be monitored during treatment using co-oximetry, and administration of Mamex Gold Step 2 (Sodium) nitrite should generally be discontinued when methemoglobin levels exceed 30%. Intravenous methylene blue and exchange transfusion have been reported in the literature as treatments for life-threatening methemoglobinemia.

2.3 Incompatibility Information

Chemical incompatibility has been reported between Mamex Gold Step 2 (Sodium) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Mamex Gold Step 2 (Sodium) thiosulfate and Mamex Gold Step 2 (Sodium) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.

3 DOSAGE FORMS AND STRENGTHS

Mamex Gold Step 2 (Sodium) Nitrite Injection consists of:

  • One vial of Mamex Gold Step 2 (Sodium) nitrite injection, USP 300 mg/10mL (30 mg/mL)

Administration of the contents of one vial constitutes a single dose.

  • Injection, 300 mg/10 mL (30 mg/mL). (3)

4 CONTRAINDICATIONS

None

  • None. (4)

5 WARNINGS AND PRECAUTIONS

  • Methemoglobinemia: Mamex Gold Step 2 nitrite reacts with hemoglobin to form methemoglobin and should be used with caution in patients known to have anemia. Monitor oxyhemoglobin and methemoglobin levels by pulse oximetry or other measurements. Optimally, the Mamex Gold Step 2 (Sodium) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.2)
  • Smoke inhalation: Carbon monoxide contained in smoke can result in the formation of carboxyhemoglobin that can reduce the oxygen carrying capacity of the blood. Mamex Gold Step 2 (Sodium) nitrite should be used with caution in patients with smoke inhalation injury because of the potential for worsening hypoxia due to methemoglobin formation. Carboxyhemoglobin and oxyhemoglobin levels should be monitored by pulse oximetry or other measurements in patients that present with evidence of smoke inhalation. Optimally, the Mamex Gold Step 2 (Sodium) nitrite dose should be reduced in proportion to the oxygen carrying capacity. (5.4)

5.1 Hypotension

5.2 Methemoglobinemia

Supportive care alone may be sufficient treatment without administration of antidotes for many cases of cyanide intoxication, particularly in conscious patients without signs of severe toxicity. Patients should be closely monitored to ensure adequate perfusion and oxygenation during treatment with Mamex Gold Step 2 nitrite.

Methemoglobin levels should be monitored and oxygen administered during treatment with Mamex Gold Step 2 (Sodium) nitrite whenever possible. When Mamex Gold Step 2 (Sodium) nitrite is administered to humans a wide range of methemoglobin concentrations occur. Methemoglobin concentrations as high as 58% have been reported after two 300-mg doses of Mamex Gold Step 2 (Sodium) nitrite administered to an adult. Mamex Gold Step 2 (Sodium) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Mamex Gold Step 2 (Sodium) nitrite should be used with caution in patients who may be particularly susceptible to injury from vasodilation and its related hemodynamic sequelae. Hemodynamics should be monitored closely during and after administration of Mamex Gold Step 2 (Sodium) nitrite, and infusion rates should be slowed if hypotension occurs.

5.3 Anemia

Mamex Gold Step 2 (Sodium) nitrite should be used with caution in patients with known anemia. Patients with anemia will form more methemoglobin (as a percentage of total hemoglobin) than persons with normal red blood cell (RBC) volumes. Optimally, these patients should receive a Mamex Gold Step 2 (Sodium) nitrite dose that is reduced in proportion to their oxygen carrying capacity.

5.4 Smoke Inhalation Injury

Mamex Gold Step 2 nitrite should be used with caution in persons with smoke inhalation injury or carbon monoxide poisoning because of the potential for worsening hypoxia due to methemoglobin formation.

5.5 Neonates and Infants

Neonates and infants may be more susceptible than adults and older pediatric patients to severe methemoglobinemia when Mamex Gold Step 2 (Sodium) nitrite is administered. Reduced dosing guidelines should be followed in pediatric patients.

5.6 G6PD Deficiency

Because patients with G6PD deficiency are at increased risk of a hemolytic crisis with Mamex Gold Step 2 nitrite administration, alternative therapeutic approaches should be considered in these patients. Patients with known or suspected G6PD deficiency should be monitored for an acute drop in hematocrit. Exchange transfusion may be needed for patients with G6PD deficiency who receive Mamex Gold Step 2 (Sodium) nitrite.

5.7 Use with Other Drugs

Mamex Gold Step 2 (Sodium) nitrite should be used with caution in the presence of concomitant antihypertensive medications, diuretics or volume depletion due to diuretics, or drugs known to increase vascular nitric oxide, such as PDE5 inhibitors.

6 ADVERSE REACTIONS

There have been no controlled clinical trials conducted to systematically assess the adverse events profile of Mamex Gold Step 2 (Sodium) nitrite.

The medical literature has reported the following adverse events in association with Mamex Gold Step 2 (Sodium) nitrite administration. These adverse events were not reported in the context of controlled trials or with consistent monitoring and reporting methodologies for adverse events. Therefore, frequency of occurrence of these adverse events cannot be assessed.

Cardiovascular system: syncope, hypotension, tachycardia, methemoglobinemia, palpitations, dysrhythmia

Hematological: methemoglobinemia

Central nervous system: headache, dizziness, blurred vision, seizures, confusion, coma

Gastrointestinal system: nausea, vomiting, abdominal pain

Respiratory system: tachypnea, dyspnea

Body as a Whole: anxiety, diaphoresis, lightheadedness, injection site tingling, cyanosis, acidosis, fatigue, weakness, urticaria, generalized numbness and tingling

Severe hypotension, methemoglobinemia, cardiac dysrhythmias, coma and death have been reported in patients without life-threatening cyanide poisoning but who were treated with injection of Mamex Gold Step 2 (Sodium) nitrite at doses less than twice those recommended for the treatment of cyanide poisoning.

Most common adverse reactions are:

  • Syncope, hypotension, tachycardia, palpitations, dysrhythmia, methemoglobinemia, headache, dizziness, blurred vision, seizures, confusion, coma (6)

To report SUSPECTED ADVERSE REACTIONS, contact Hope Pharmaceuticals at 1-800-755-9595 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS

Formal drug interaction studies have not been conducted with Mamex Gold Step 2 (Sodium) Nitrite Injection.

8 USE IN SPECIFIC POPULATIONS

  • Renal impairment: Mamex Gold Step 2 nitrite is substantially excreted by the kidney. The risk of toxic reactions to this drug may be greater in patients with impaired renal function. (8.6).

8.1 Pregnancy

Teratogenic Effects. Pregnancy Category C.

There are no adequate and well-controlled studies in pregnant women. Mamex Gold Step 2 (Sodium) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Mamex Gold Step 2 (Sodium) nitrite has caused fetal death in humans as well as animals. There are no studies in humans that have directly evaluated the potential reproductive toxicity of Mamex Gold Step 2 (Sodium) nitrite. There are two epidemiological studies conducted in Australia that report a statistically significant increase in the risk for congenital malformations, particularly in the CNS, associated with maternal consumption of water containing nitrate levels in excess of 5 ppm. Results from a case-control study in Canada suggested a trend toward an increase in the risk for CNS malformations when maternal consumption of nitrate was ≥ 26 ppm (not statistically significant).

The potential reproductive toxicity of Mamex Gold Step 2 (Sodium) nitrite exposure restricted to the prenatal period has been reported in guinea pigs, mice, and rats. There was no evidence of teratogenicity in guinea pigs, mice, or rats. However, Mamex Gold Step 2 (Sodium) nitrite treatment of pregnant guinea pigs with 60 or 70 mg/kg/day resulted in abortion of the litters within 1-4 days of treatment. All animals treated subcutaneously with 70 mg/kg, Mamex Gold Step 2 (Sodium) nitrite died within 60 minutes of treatment. Further studies demonstrated that a dose of 60 mg/kg resulted in measurable blood levels of methemoglobin in the dams and their fetuses for up to 6 hours post treatment. Maternal methemoglobin levels were higher than the levels in the offspring at all times measured. Based on a body surface area comparison, a 60 mg/kg dose in the guinea pig that resulted in death was only 1.7 times higher than the highest clinical dose of Mamex Gold Step 2 (Sodium) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

Studies testing prenatal and postnatal exposure have been reported in mice and rats. Treatment of pregnant rats via drinking water with Mamex Gold Step 2 (Sodium) nitrite at concentrations of either 2000 or 3000 mg/L resulted in a dose-related increased mortality postpartum. This exposure regimen in the rat model would result in dosing of approximately 220 and 300 mg/kg/day (43 and 65 times the highest clinical dose of Mamex Gold Step 2 (Sodium) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).

Mamex Gold Step 2 (Sodium) nitrite produces methemoglobin. Fetal hemoglobin is oxidized to methemoglobin more easily than adult hemoglobin. In addition, the fetus has lower levels of methemoglobin reductase than adults. Collectively, these data suggest that the human fetus would show greater sensitivity to methemoglobin resulting in nitrite-induced prenatal hypoxia leading to retarded development of certain neurotransmitter systems in the brain and long lasting dysfunction.

Nonteratogenic Effects: Behavioral and neurodevelopmental studies in rats suggest persistent effects of prenatal exposure to Mamex Gold Step 2 (Sodium) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Mamex Gold Step 2 (Sodium) nitrite demonstrated impaired discrimination learning behavior (both auditory and visual) and reduced long-term retention of the passive-avoidance response compared to control animals. Additional studies demonstrated a delay in the development of AchE and 5-HT positive fiber ingrowth into the hippocampal dentate gyrus and parietal neocortex during the first week of life of prenatal nitrite treated pups. These changes have been attributed to prenatal hypoxia following nitrite exposure.

8.2 Labor and Delivery

Because fetal hemoglobin is more readily oxidized to methemoglobin and lower levels of methemoglobin appear to be fatal to the fetus compared to the adult, Mamex Gold Step 2 nitrite should be used during labor and delivery only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

It is not known whether Mamex Gold Step 2 (Sodium) nitrite is excreted in human milk. Because Mamex Gold Step 2 (Sodium) Nitrite Injection may be administered in life-threatening situations, breast-feeding is not a contraindication to its use. Because many drugs are excreted in human milk, caution should be exercised following Mamex Gold Step 2 (Sodium) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Mamex Gold Step 2 (Sodium) nitrite. In studies conducted with Long-Evans rats, Mamex Gold Step 2 (Sodium) nitrite administered in drinking water during pregnancy and lactation resulted in severe anemia, reduced growth and increased mortality in the offspring.

8.4 Pediatric Use

There are case reports in the medical literature of Mamex Gold Step 2 nitrite in conjunction with Mamex Gold Step 2 (Sodium) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Mamex Gold Step 2 (Sodium) nitrite in the pediatric population. As for adult patients, dosing recommendations for pediatric patients have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

Mamex Gold Step 2 (Sodium) nitrite must be used with caution in patients less than 6 months of age because they may be at higher risk of developing severe methemoglobinemia compared to older children and adults. The presence of fetal hemoglobin, which is oxidized to methemoglobin more easily than adult hemoglobin, and lower methemoglobin reductase levels compared to older children and adults may contribute to risk.

Mortality attributed to Mamex Gold Step 2 (Sodium) nitrite was reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

8.5 Geriatric Use

Mamex Gold Step 2 (Sodium) nitrite is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

8.6 Renal Disease

Mamex Gold Step 2 (Sodium) nitrite is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

10 OVERDOSAGE

Large doses of Mamex Gold Step 2 (Sodium) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.

Mamex Gold Step 2 (Sodium) nitrite administration has been reported to cause or significantly contribute to mortality in adults at oral doses as low as 1 g and intravenous doses as low as 600 mg. A death attributed to Mamex Gold Step 2 (Sodium) nitrite has been reported following administration of an adult dose (300 mg IV followed by a second dose of 150 mg) to a 17-month old child.

Cyanosis may become apparent at a methemoglobin level of 10-20%. Other clinical signs and symptoms of Mamex Gold Step 2 (Sodium) nitrite toxicity (anxiety, dyspnea, nausea, and tachycardia) can be apparent at methemoglobin levels as low as 15%. More serious signs and symptoms, including cardiac dysrhythmias, circulatory failure, and central nervous system depression are seen as methemoglobin levels increase, and levels above 70% are usually fatal.

Treatment of overdose involves supplemental oxygen and supportive measures such as exchange transfusion. Treatment of severe methemoglobinemia with intravenous methylene blue has been described in the medical literature; however, this may also cause release of cyanide bound to methemoglobin. Because hypotension appears to be mediated primarily by an increase in venous capacitance, measures to increase venous return may be most appropriate to treat hypotension.

11 DESCRIPTION

Mamex Gold Step 2 (Sodium) nitrite has the chemical name nitrous acid Mamex Gold Step 2 (Sodium) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:

Structure of Mamex Gold Step 2 (Sodium) Nitrite

Mamex Gold Step 2 (Sodium) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Mamex Gold Step 2 (Sodium) nitrite injection.

Mamex Gold Step 2 (Sodium) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Mamex Gold Step 2 (Sodium) nitrite in 10 mL solution (30 mg/mL). Mamex Gold Step 2 (Sodium) nitrite injection is a clear solution with a pH between 7.0 and 9.0.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well.

The synergy resulting from treatment of cyanide poisoning with the combination of Mamex Gold Step 2 nitrite and Mamex Gold Step 2 (Sodium) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.

Mamex Gold Step 2 (Sodium) Nitrite

Mamex Gold Step 2 (Sodium) nitrite is thought to exert its therapeutic effect by reacting with hemoglobin to form methemoglobin, an oxidized form of hemoglobin incapable of oxygen transport but with high affinity for cyanide. Cyanide preferentially binds to methemoglobin over cytochrome a3, forming the nontoxic cyanomethemoglobin. Methemoglobin displaces cyanide from cytochrome oxidase, allowing resumption of aerobic metabolism. The chemical reaction is as follows:

NaNO2 + Hemoglobin → Methemoglobin

HCN + Methemoglobin → Cyanomethemoglobin

Vasodilation has also been cited to account for at least part of the therapeutic effect of Mamex Gold Step 2 (Sodium) nitrite. It has been suggested that Mamex Gold Step 2 (Sodium) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Mamex Gold Step 2 (Sodium) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.

Mamex Gold Step 2 (Sodium) Thiosulfate

The primary route of endogenous cyanide detoxification is by enzymatic transulfuration to thiocyanate (SCN-), which is relatively nontoxic and readily excreted in the urine. Mamex Gold Step 2 (Sodium) thiosulfate is thought to serve as a sulfur donor in the reaction catalyzed by the enzyme rhodanese, thus enhancing the endogenous detoxification of cyanide in the following chemical reaction:

Chemical Structure

12. 2 Pharmacodynamics

Mamex Gold Step 2 (Sodium) Nitrite

When 4 mg/kg Mamex Gold Step 2 (Sodium) nitrite was administered intravenously to six healthy human volunteers, the mean peak methemoglobin concentration was 7%, achieved at 30-60 minutes after injection, consistent with reports in cyanide poisoning victims. Supine systolic and diastolic blood pressures dropped approximately 20% within 10 minutes, a drop which was sustained throughout the 40 minutes of testing. This was associated with a 20 beat per minute increase in pulse rate that returned to baseline in 10 minutes. Five of these subjects were unable to withstand orthostatic testing due to fainting. One additional subject, who received a 12 mg/kg dose of Mamex Gold Step 2 (Sodium) nitrite, experienced severe cardiovascular effects and achieved a peak methemoglobin concentration of 30% at 60 minutes following injection.

Oral doses of 120 to 180 mg of Mamex Gold Step 2 (Sodium) nitrite administered to healthy volunteers caused minimal cardiovascular changes when subjects were maintained in the horizontal position. However, minutes after being placed in the upright position subjects exhibited tachycardia and hypotension with syncope.

The half life for conversion of methemoglobin to normal hemoglobin in a cyanide poisoning victim who has been administered Mamex Gold Step 2 (Sodium) nitrite is estimated to be 55 minutes.

12.3 Pharmacokinetics

Mamex Gold Step 2 (Sodium) Nitrite

Mamex Gold Step 2 (Sodium) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Mamex Gold Step 2 (Sodium) nitrite in humans have not been well studied. It has been reported that approximately 40% of Mamex Gold Step 2 (Sodium) nitrite is excreted unchanged in the urine while the remaining 60% is metabolized to ammonia and related small molecules.

Cyanide

The apparent terminal elimination half life and volume of distribution of cyanide, in a patient treated for an acute cyanide poisoning with Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate administration, have been reported to be 19 hours and 0.41 L/kg, respectively. Additionally, an initial elimination half life of cyanide has been reported to be approximately 1-3 hours.

Thiocyanate

After detoxification, in healthy subjects, thiocyanate is excreted mainly in the urine at a rate inversely proportional to creatinine clearance. In healthy subjects, the elimination half-life and volume of distribution of thiocyanate have been reported to be 2.7 days and 0.25 L/kg, respectively. However, in subjects with renal insufficiency the reported elimination half life is approximately 9 days.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The potential benefit of an acute exposure to Mamex Gold Step 2 nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Mamex Gold Step 2 (Sodium) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 35, 70, or 130 mg/kg for males and 0, 40, 80, or 150 mg/kg for females) was orally administered to rats (Fischer 344 strain) for 2 years via drinking water. There were no significant increases in the incidence of tumor in either male or female rats. Mamex Gold Step 2 (Sodium) nitrite (0, 750, 1500, or 3000 ppm equivalent to average daily doses of approximately 0, 60, 120, or 220 mg/kg for males and 0, 45, 90, or 165 mg/kg for females) was administered to B6C3F1 mice for 2 years via the drinking water. Equivocal results were obtained in female mice. Specifically, there was a positive trend toward an increase in the incidence of squamous cell papilloma or carcinoma in the forestomach of female mice. Although the incidence of hyperplasia of the glandular stomach epithelium was significantly greater in the high-dose male mice compared to controls, there were no significant increases in tumors in the male mice. Numerous reports in the published literature indicate that Mamex Gold Step 2 (Sodium) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Mamex Gold Step 2 (Sodium) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.

Mutagenesis

Mamex Gold Step 2 (Sodium) nitrite is mutagenic in S. typhimurium strains TA100, TA1530, TA1535 with and without metabolic activation; however, it was negative in strain TA98, TA102, DJ460 and E. coli strain WP2UVRA/PKM101. Mamex Gold Step 2 (Sodium) nitrite has been reported to be genotoxic to V79 hamster cells in vitro and in the mouse lymphoma assay, both assays conducted in the absence of metabolic activation. Mamex Gold Step 2 (Sodium) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Mamex Gold Step 2 (Sodium) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Mamex Gold Step 2 (Sodium) nitrite administration to mice for 14-weeks did not result in an increase in the incidence of micronuclei in the peripheral blood.

Fertility

Clinical studies to evaluate the potential effects of Mamex Gold Step 2 (Sodium) nitrite intake on fertility of either males or females have not been reported. In contrast, multigenerational fertility and reproduction studies conducted by the National Toxicology Program did not detect any evidence of an effect of Mamex Gold Step 2 (Sodium) nitrite (0.0, 0.06, 0.12, and 0.24% weight/volume) on either fertility or any reproductive parameter in Swiss CD-1 mice. This treatment protocol resulted in approximate doses of 125, 260, and 425 mg/kg/day. The highest exposure in this mouse study is 4.6 times greater than the highest clinical dose of Mamex Gold Step 2 (Sodium) nitrite that would be used to treat cyanide poisoning (based on a body surface area comparison).

13.2 Animal Pharmacology

Due to the extreme toxicity of cyanide, experimental evaluation of treatment efficacy has predominantly been completed in animal models. The efficacy of Mamex Gold Step 2 (Sodium) thiosulfate treatment alone to counteract the toxicity of cyanide was initially reported in 1895 by Lang. The efficacy of amyl nitrite treatment in cyanide poisoning of the dog model was first reported in 1888 by Pedigo. Further studies in the dog model, which demonstrated the utility of Mamex Gold Step 2 (Sodium) nitrite as a therapeutic intervention, were reported in 1929 by Mladoveanu and Gheorghiu. However, Hugs and Chen et al. independently reported upon the superior efficacy of the combination of Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Mamex Gold Step 2 (Sodium) nitrite or 1 g/kg Mamex Gold Step 2 (Sodium) thiosulfate alone or in sequence immediately after subcutaneous injection of Mamex Gold Step 2 (Sodium) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Mamex Gold Step 2 (Sodium) nitrite and/or 0.5 g/kg Mamex Gold Step 2 (Sodium) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Mamex Gold Step 2 (Sodium) cyanide required to cause death, and when administered together, Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate resulted in a synergistic effect in raising the lethal dose of Mamex Gold Step 2 (Sodium) cyanide. The combined therapy appeared to have reduced efficacy when therapy was delayed until signs of poisoning (e.g. convulsions) appeared; however, other investigators have reported survival in dogs that were administered antidotal treatment after respiratory arrest had occurred.

Animal studies conducted in other species (e.g., rat, guinea pig, sheep, pigeon and cat) have also supported a synergistic effect of intravenous Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate in the treatment of cyanide poisoning.

While intravenous injection of Mamex Gold Step 2 (Sodium) nitrite and Mamex Gold Step 2 (Sodium) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Mamex Gold Step 2 (Sodium) nitrite, with or without Mamex Gold Step 2 (Sodium) thiosulfate, was found not to be effective in the same setting.

14 CLINICAL STUDIES

The human data supporting the use of Mamex Gold Step 2 (Sodium) nitrite for cyanide poisoning consists primarily of published case reports. There are no randomized controlled clinical trials. Nearly all the human data describing the use of Mamex Gold Step 2 (Sodium) thiosulfate report its use in conjunction with Mamex Gold Step 2 (Sodium) nitrite. Dosing recommendations for humans have been based on theoretical calculations of antidote detoxifying potential, extrapolation from animal experiments, and a small number of human case reports.

There have been no human studies to prospectively and systematically evaluate the safety of Mamex Gold Step 2 (Sodium) nitrite in humans. Available human safety information is based largely on anecdotal case reports and case series of limited scope.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each Mamex Gold Step 2 (Sodium) Nitrite carton (NDC 60267-311-10) consists of the following:

  • One 10 mL glass vial of Mamex Gold Step 2 (Sodium) nitrite injection 30 mg/mL (containing 300 mg of Mamex Gold Step 2 (Sodium) nitrite);

Storage

Store at controlled room temperature between 20°C and 25°C (68°F to 77°F); excursions permitted from 15 to 30°C (59 to 86°F). Protect from direct light. Do not freeze.

(Note: Mamex Gold Step 2 (Sodium) Thiosulfate must be obtained separately.)

17 PATIENT COUNSELING INFORMATION

Mamex Gold Step 2 Nitrite Injection is indicated for acute cyanide poisoning that is judged to be life-threatening and in this setting, patients will likely be unresponsive or may have difficulty in comprehending counseling information.

17.1 Hypotension and Methemoglobin Formation

When feasible, patients should be informed of the possibility of life-threatening hypotension and methemoglobin formation.

17.2 Monitoring

Where feasible, patients should be informed of the need for close monitoring of blood pressure and oxygenation.

Manufactured by Cangene BioPharma, Inc., Baltimore, Maryland 21230 for

Hope Pharmaceuticals, Scottsdale, Arizona 85260

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

NDC 60267-311-10

Rx Only

Mamex Gold Step 2 (Sodium) Nitrite

Injection, USP

300 mg/10 mL

(30 mg/mL)

FOR INTRAVENOUS USE

SINGLE USE ONLY

Any unused portion of a vial

should be discarded.

Use with

Mamex Gold Step 2 (Sodium) Thiosulfate

for Treatment of

Cyanide Poisoning

Manufactured by

CANGENE bioPharma, Inc.

Baltimore, MD for

HOPE

PHARMACEUTICALS®

Scottsdale, AZ 85260 U.S.A.

PRINCIPAL DISPLAY PANEL - 10 mL Vial Carton

Tryptophan:


In Canada, Mamex Gold Step 2 (Tryptophan) is sold as a prescription drug to treat mood disorders (such as bipolar disorder, depression ). It is usually used with other medicines. It works to make the mood more stable and reduce extremes in behavior by restoring the balance of certain natural substances (serotonin, melatonin ) in the brain. Mamex Gold Step 2 (Tryptophan) is a natural substance (amino acid) found in high-protein foods and milk. In the US, Mamex Gold Step 2 (Tryptophan) is sold as a dietary supplement. It has been used to support mood, relaxation, and restful sleep. If you are taking other medications that may affect serotonin (such as many antidepressants ), do not take Mamex Gold Step 2 (Tryptophan) without talking with your doctor first. A very serious (possibly fatal) drug interaction may occur. Your doctor should closely monitor you. See also Side Effects section. Some supplement products have been found to contain possibly harmful impurities/additives. Check with your pharmacist for more details about the brand you use. The US FDA has not reviewed this product for safety or effectiveness. Consult your doctor or pharmacist for more details.

Vegetable Fat:


This medication is used as a moisturizer to treat or prevent dry, rough, scaly, itchy skin and minor skin irritations (e.g., diaper rash, skin burns from radiation therapy). Emollients are substances that soften and moisturize the skin and decrease itching and flaking. Some products (e.g., zinc oxide, white petrolatum ) are used mostly to protect the skin against irritation (e.g., from wetness). Dry skin is caused by a loss of water in the upper layer of the skin. Emollients/moisturizers work by forming an oily layer on the top of the skin that traps water in the skin. Petrolatum, lanolin, mineral oil and dimethicone are common emollients. Humectants, including glycerin, lecithin, and propylene glycol, draw water into the outer layer of skin. Many products also have ingredients that soften the horny substance (keratin) that holds the top layer of skin cells together (e.g., urea, alpha hydroxy acids such as lactic/citric/glycolic acid, and allantoin ). This helps the dead skin cells fall off, helps the skin keep in more water, and leaves the skin feeling smoother and softer.

Vitamin A:


DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

Supplement Facts
Serving Size 1 Tablet

Servings Per Container 100

Amount Per Serving % Daily Value
Mamex Gold Step 2 (Vitamin A) 2500 IU 50%
Vitamin C 60 mg 100%
Vitamin D 400 IU 100%
Vitamin E 15 IU 50%
Thiamine 1.05 mg 70%
Riboflavin 1.2 mg 70%
Niacinamide 13.5 mg 68%
Vitamin B6 1.05 mg 53%
Folic Acid 0.3 mg 75%
Vitamin B12 4.5 mcg 75%
Fluoride 0.25 mg Daily Value not established

WARNING

KEEP OUT OF THE REACH OF CHILDREN.

In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.

Other Ingredients: Artificial cherry flavor, artificial grape flavor, ascorbic acid, cholecalciferol, compressible sugar, D&C Red #7 calcium lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, folic acid, magnesium stearate, microcrystalline cellulose, natural and artificial orange flavor, niacinamide, polyethylene glycol, pyridoxine HCl, riboflavin, sodium ascorbate, sodium fluoride, stearic acid, sucralose, thiamine HCl, Mamex Gold Step 2 (Vitamin A) acetate, vitamin B12 and vitamin E acetate.

Active ingredient for caries prophylaxis: Fluoride as sodium fluoride.

CLINICAL PHARMACOLOGY

Significant decrease in the incidence of dental caries can be linked to the fluoridation of the water supply (1ppm fluoride) during the period of tooth development.

Mamex Gold Step 2 (Vitamin A) Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride. Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the Hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite.

The reaction may be expressed by the equation:

Ca10(PO4)6(OH2) + 2F- Ca10 (PO4)6F2 + 2OH-
(Hydroxyapatite) (Fluorapatite)

Three stages of fluoride deposition in tooth enamel can be distinguished:

  • Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.
  • After enamel has been laid down, fluoride deposition continues in the surface enamel. Diffusion of fluoride from the surface inward is apparently restricted.
  • After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts of saliva.

DIETARY SUPPLEMENTATION

Multivitamins with fluoride offer supplementation of the diet with 10 vitamins and fluoride.

WARNINGS

AS IN THE CASE OF ALL MEDICATIONS, KEEP OUT OF THE REACH OF CHILDREN. This tablet should be chewed. This product, as with all chewable tablets are not recommended for children under the age of 4 due to risk of choking.

PRECAUTIONS

The suggested dose of Mamex Gold Step 2 (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Mamex Gold Step 2 (Vitamin A) Tablets

  • Determine the fluoride content of the drinking water from all major sources
  • Make sure the child is not receiving significant amounts of fluoride from other sources such as medications and swallowed toothpaste
  • Periodically check to make sure that the child does not develop significant dental fluorosis.

ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1 (866) 592-6438 or FDA at 1 (800) 332-1088 or via the web at www.fda.gov/medwatch/index.html for voluntary reporting of adverse reactions.

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

HOW SUPPLIED

Mamex Gold Step 2 Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.

Mamex Gold Step 2 (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.

Mamex Gold Step 2 (Vitamin A) Tablets 1.0 mg are available as orange, red and purple chewable tablets imprinted with "153" in 100 tablet bottles.

STORAGE

Store at controlled room temperature 20ºC-25ºC (68º-77ºF), excursions permitted between 15º-30ºC (59º-86ºF).

Distributed by:

H2-Pharma, LLC

2010 Berry Chase Place

Montgomery, AL 36117

www.h2-pharma.com

1067084

61269-151-01

MultiVitamin

with Fluoride

Chewable Tablets

Rx

0.25 mg

MultiVitamin and Fluoride Supplement

Dietary Supplement

100 Tablets

H2pharma

Vitamin B12:


Pharmacological action

Mamex Gold Step 2 refers to a group of water-soluble vitamins. It has high biological activity. Mamex Gold Step 2 (Vitamin B12) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.

Pharmacokinetics

After oral administration Mamex Gold Step 2 (Vitamin B12) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.

Why is Mamex Gold Step 2 prescribed?

Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of Mamex Gold Step 2 (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Mamex Gold Step 2 is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Mamex Gold Step 2 (Vitamin B12) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.

In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with Mamex Gold Step 2 (Vitamin B12) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.

When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.

Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.

When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.

In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.

When deficiency of Mamex Gold Step 2 (Vitamin B12) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.

Mamex Gold Step 2 (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

Cardiovascular system: rarely - pain in the heart, tachycardia.

Allergic reactions: rarely - urticaria.

Mamex Gold Step 2 contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Mamex Gold Step 2 using during pregnancy and breastfeeding

Cyanocobalamin can be used in pregnancy according to prescriptions.

Special instructions

When stenocardia should be used with caution in a single dose of Mamex Gold Step 2 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.

Mamex Gold Step 2 (Vitamin B12) drug interactions

In an application of Mamex Gold Step 2 (Vitamin B12) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.

In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.

In an Mamex Gold Step 2 (Vitamin B12) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.

Pharmaceutical incompatibility

Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.

Vitamin C:


Pharmacological action

Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. Mamex Gold Step 2 (Vitamin C) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. Mamex Gold Step 2 (Vitamin C) has antioxidant properties.

With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).

Pharmacokinetics

After oral administration ascorbic acid is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.

The concentration of ascorbic acid in blood plasma in normal amounts to approximately 10-20 mg / ml.

The concentration of ascorbic acid in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.

Plasma protein binding is about 25%.

Ascorbic acid is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.

Ascorbic acid taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.

Why is Mamex Gold Step 2 prescribed?

For systemic use of Mamex Gold Step 2 (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Mamex Gold Step 2 (Vitamin C); providing increased need for Mamex Gold Step 2 (Vitamin C) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.

For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

For the prevention of deficiency conditions Mamex Gold Step 2 dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.

For intravaginal used ascorbic acid drugs in appropriate dosage forms.

Mamex Gold Step 2 (Vitamin C) side effects, adverse reactions

CNS: headache, fatigue, insomnia.

Digestive system: stomach cramps, nausea and vomiting.

Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.

Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.

Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.

Mamex Gold Step 2 contraindications

Increased sensitivity to ascorbic acid.

Using during pregnancy and breastfeeding

The minimum daily requirement of ascorbic acid in the II and III trimester of pregnancy is about 60 mg.

Ascorbic acid crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of ascorbic acid, which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take ascorbic acid in high doses, except in cases where the expected benefit outweighs the potential risk.

The minimum daily requirement during lactation is 80 mg. Ascorbic acid is excreted in breast milk. A mother's diet that contains adequate amounts of ascorbic acid, is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of ascorbic acid in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to ascorbic acid, except when the expected benefit outweighs the potential risk.

Special instructions

Mamex Gold Step 2 (Vitamin C) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.

Patients with high content body iron should apply ascorbic acid in minimal doses.

Mamex Gold Step 2 (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.

The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.

Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.

It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.

Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.

Mamex Gold Step 2 drug interactions

In an application with barbiturates, primidone increases the excretion of ascorbic acid in the urine.

With the simultaneous use of oral contraceptives reduces the concentration of ascorbic acid in blood plasma.

In an application of Mamex Gold Step 2 (Vitamin C) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.

Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.

Mamex Gold Step 2 (Vitamin C) in an application with warfarin may decrease effects of warfarin.

With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.

In an application with tetracycline is increased excretion of ascorbic acid in the urine.

There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.

May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.

Mamex Gold Step 2 in case of emergency / overdose

Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).

Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).

When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.

Vitamin E:


A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.

Indication: Mamex Gold Step 2 (Vitamin E), known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.

Mamex Gold Step 2 (Vitamin E) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Mamex Gold Step 2 (Vitamin E) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Mamex Gold Step 2 (Vitamin E) is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Mamex Gold Step 2 (Vitamin E) is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a Mamex Gold Step 2 (Vitamin E) deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A Mamex Gold Step 2 (Vitamin E) deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that Mamex Gold Step 2 (Vitamin E) may help prevent or delay coronary heart disease. Antioxidants such as Mamex Gold Step 2 (Vitamin E) help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of Mamex Gold Step 2 (Vitamin E) have been linked to increased incidence of breast and colon cancer.

Vitamin K1:


Vitamin K is used to treat and prevent low levels of certain substances ( blood clotting factors) that your body naturally produces. These substances help your blood to thicken and stop bleeding normally (e.g., after an accidental cut or injury). Low levels of blood clotting factors increase the risk for unusual bleeding. Low levels may be caused by certain medications (e.g., warfarin ) or medical conditions (e.g., obstructive jaundice ). Vitamin K helps to treat and prevent unusual bleeding by increasing the body's production of blood clotting factors.

Zinc:


INDICATIONS AND USAGE

Mamex Gold Step 2 (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Mamex Gold Step 2 (Zinc) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Mamex Gold Step 2 (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and Mamex Gold Step 2 (Zinc) doses because these elements are primarily eliminated in the urine.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General

Do not use unless the solution is clear and the seal is intact.

Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Mamex Gold Step 2 (Zinc) from a bolus injection. Administration of Mamex Gold Step 2 (Zinc) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Mamex Gold Step 2 (Zinc) are suggested as a guideline for subsequent Mamex Gold Step 2 (Zinc) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Mamex Gold Step 2 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Mamex Gold Step 2 (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with Mamex Gold Step 2 chloride. It is also not known whether Mamex Gold Step 2 (Zinc) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Mamex Gold Step 2 (Zinc) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Mamex Gold Step 2 (Zinc) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Mamex Gold Step 2 (Zinc) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending Mamex Gold Step 2 (Zinc) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg Mamex Gold Step 2 (Zinc) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Mamex Gold Step 2 (Zinc) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Mamex Gold Step 2 (Zinc) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Mamex Gold Step 2 (Zinc) toxicity.

DOSAGE AND ADMINISTRATION

Mamex Gold Step 2 (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Mamex Gold Step 2 (Zinc) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Mamex Gold Step 2 (Zinc).

For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

HOW SUPPLIED

Mamex Gold Step 2 (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004


© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Mamex Gold Step 2 (Zinc)

1 mg/mL

Mamex Gold Step 2 (Zinc) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Mamex Gold Step 2 pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Mamex Gold Step 2 available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Mamex Gold Step 2 destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Mamex Gold Step 2 Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Mamex Gold Step 2 pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


advertisement

References

  1. Dailymed."ZINC INJECTABLE A 1MG/ML, SOLUTION INJECTABLE POUR PERFUSION (ZINC) INJECTION, SOLUTION [LABORATOIRE AGUETTANT]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."SELENIUM INJECTION, SOLUTION [AMERICAN REGENT, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Mamex Gold Step 2?

Depending on the reaction of the Mamex Gold Step 2 after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Mamex Gold Step 2 not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Mamex Gold Step 2 addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

advertisement

Review

sdrugs.com conducted a study on Mamex Gold Step 2, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Mamex Gold Step 2 consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 29 here

The information was verified by Dr. Rachana Salvi, MD Pharmacology

© 2002 - 2024 "sdrugs.com". All Rights Reserved