Novamil S2

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Novamil S2 uses

Novamil S2 consists of Calcium Phosphate Tribasic, Choline Bitartrate, Copper Sulfate, Dextrose, Ethyl Vanillin, Ferrous Sulfate, Folic Acid, Lactose, Lecithin, Lecithin (Soy), Magnesium Oxide, Maltodextrin, Manganese Sulfate, Palm Oil, Potassium Hydroxide, Potassium Iodide, Potassium Phosphate Dibasic, Skim Milk, Sodium Citrate, Soy Oil, Starch, Vitamin A, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B3 (Niacine), Vitamin B5 (Pantothenic Acid), Vitamin B6, Vitamin C, Vitamin D3, Vitamin E, Vitamin E (Tocopherols Mixed), Vitamin H (Biotin), Vitamin K1, Zinc Sulfate.

Calcium Phosphate Tribasic:



Active Ingredients: Novamil S2 (Calcium Phosphate Tribasic) 19%, Colloidal Silicon Dioxide 2.5%

Purpose: Anticavity

Keep out of reach of children under 6 years old

- Supervise children as necessary until being capable of using without supervision

- Instruct children under 6 years old in good brushing and rinsing habits

If more than used for brushing is accidentally swallowed, get medical help or contact a Poison Control Center right away

Inactive Ingredients: Xylitol, Erythritol, Chitosan, D-Sorbitol Solution, L-Menthol, Lactic Acid

- Brush teeth twice daily or after each meal as directed by a dentist or doctor

Choline Bitartrate:


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). Novamil S2 (Choline Bitartrate) is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. Novamil S2 (Choline Bitartrate) also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. Novamil S2 (Choline Bitartrate) has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. Novamil S2 (Choline Bitartrate) 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 Sulfate:



Water-Resistant Protection Without Bandaging

Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to Novamil S2 (Copper Sulfate) 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 Novamil S2 (Copper Sulfate)®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess Novamil S2 (Copper Sulfate)® onto hair since contact with Novamil S2 (Copper Sulfate)® may cause some hair loss. Do not contaminate feed.

NOTE: Novamil S2 (Copper Sulfate)® 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:

Novamil S2 (Copper Sulfate) Naphthenate...37.5% w/w

INACTIVE INGREDIENTS:

Inert Ingredients...62.5% w/w

Total... 100.0%

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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

Dextrose:


INDICATIONS AND USAGE

70% Novamil S2 (Dextrose) Injection USP is indicated as a caloric component in a parenteral nutrition regimen. 70% Novamil S2 (Dextrose) Injection USP is used with an appropriate protein (nitrogen) source in the prevention of nitrogen loss or in the treatment of negative nitrogen balance in patients where: (1) the alimentary tract cannot or should not be used, (2) gastrointestinal absorption of protein is impaired, or (3) metabolic requirements for protein are substantially increased, as with extensive burns.

CONTRAINDICATIONS

The infusion of 70% Novamil S2 (Dextrose) Injection USP is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma.

Solutions containing Novamil S2 (Dextrose) may be contraindicated in patients with hypersensitivity to corn products.

WARNINGS

This injection is for compounding only, not for direct infusion.

Dilute before use to a concentration which will, when administered with an amino acid (nitrogen) source, result in an appropriate calorie to gram of nitrogen ratio and which has an osmolarity consistent with the route of administration.

Unless appropriately diluted, the infusion of hypertonic Novamil S2 (Dextrose) injection into a peripheral vein may result in vein irritation, vein damage, and thrombosis. Strongly hypertonic nutrient solutions should only be administered through an indwelling intravenous catheter with the tip located in a large central vein such as the superior vena cava.

Use of 70% Novamil S2 (Dextrose) Injection USP to prepare parenteral nutritional admixtures may be incompatible with other components, especially calcium and phosphate salts and lipid emulsions. Incompatibility of admixed components can produce precipitates which may cause particulate emboli. Use 70% Novamil S2 (Dextrose) Injection USP only to prepare formulations that are known to be stable: refer to standard texts for further information.

The administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentration.

WARNING: 70% Novamil S2 (Dextrose) Injection USP 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 µg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Prolonged infusion of isotonic or hypotonic Novamil S2 (Dextrose) in water may increase the volume of extracellular fluid and cause water intoxication.

Solutions containing Novamil S2 (Dextrose) without electrolytes should not be administered simultaneously with blood through the same infusion set because of the possibility of agglomeration.

Excessive administration of potassium-free Novamil S2 (Dextrose) solutions may result in significant hypokalemia. Serum potassium levels should be maintained and potassium supplemented as required.

In very low birth weight infants, excessive or rapid administration of Novamil S2 (Dextrose) injection may result in increased serum osmolality and possible intracerebral hemorrhage.

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PRECAUTIONS

General

This solution should be used with care in patients with hypervolemia, renal insufficiency, urinary tract obstruction, or impending or frank cardiac decompensation.

Solutions containing Novamil S2 should be used with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

Essential electrolytes, minerals, and vitamins should be supplied as needed.

Hypokalemia may develop during parenteral administration of hypertonic Novamil S2 (Dextrose) solutions. Sufficient amounts of potassium should be added to Novamil S2 (Dextrose) solutions administered to fasting patients with good renal function, especially those on digitalis therapy.

To minimize the risk of possible incompatibilities arising from mixing this solution with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration. See WARNINGS .

Do not use plastic container in series connection.

If administration of 70% Novamil S2 (Dextrose) Injection USP after admixture or dilution is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. If administration is not controlled by a pumping device, refrain from applying excessive pressure (>300mmHg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container.

This solution is intended for intravenous administration after admixture or dilution using sterile equipment. When using an automated compounding device replace all disposable components as recommended by manufacturer and at least every 24 hours.

Aseptic technique is essential with the use of sterile preparations for compounding nutritional admixtures. Discard container within 4 hours of entering closure.

Administration of hypertonic Novamil S2 (Dextrose) and amino acid solutions via central venous catheter may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure. This includes attention to solution preparation, administration and patient monitoring.

It is essential that a carefully prepared protocol, based upon current medical practice, be followed, preferably by an experienced team. The package insert of the protein (nitrogen) source should be consulted for dosage and all precautionary information.

Use only if solution is clear and container and seals are intact.

70% Novamil S2 (Dextrose) Injection USP contains no more than 25 µg/L of aluminum.

Laboratory Tests

Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require tailoring of the electrolyte pattern, in these or alternative solutions.

Drug Interactions

Caution must be exercised in the administration of 70% Novamil S2 Injection USP to patients receiving corticosteroids or corticotropin. Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store. Dispose of any unused product. See WARNINGS .

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Novamil S2 (Dextrose) Injections USP have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies with Novamil S2 Injections, USP in pregnant women and animal reproduction studies have not been conducted with this drug. Therefore, it is not known whether Novamil S2 (Dextrose) Injections USP can cause fetal harm when administered to a pregnant woman. Novamil S2 (Dextrose) Injections USP should be given during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

Intrapartum maternal intravenous infusion of glucose-containing solutions may produce maternal hyperglycemia with subsequent fetal hyperglycemia and fetal metabolic acidosis. Fetal hyperglycemia can result in increased fetal insulin levels which may result in neonatal hypoglycemia following delivery. Consider the potential risks and benefits for each specific patient before administering Novamil S2 (Dextrose) Injection, USP.

Nursing Mothers

It is not known if this drug is present in human milk. Because many drugs are present in human milk, caution should be exercised when Novamil S2 Injections USP are administered to a nursing woman.

Pediatric Use

The use of Novamil S2 (Dextrose) in pediatric patients is based on clinical practice (see DOSAGE AND ADMINISTRATION ). Because of their hypertonicity, 70% Novamil S2 (Dextrose) Injections must be diluted prior to administration.

Newborns – especially those born premature and with low birth weight - are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long term adverse effects. Hypoglycemia in the newborn can cause prolonged seizures, coma and brain damage. Hyperglycemia has been associated with intraventricular hemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, prolonged length of hospital stay, and death.

Geriatric Use

An evaluation of literature revealed no clinical experience identifying 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.

See WARNINGS .

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ADVERSE REACTIONS

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Incompatibility of admixed components can produce precipitates which may cause particulate emboli.

Hyperosmolar syndrome, resulting from excessively rapid administration of concentrated Novamil S2 (Dextrose) may cause hypovolemia, dehydration, mental confusion and/or loss of consciousness. Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a small bore needle is recommended. (See DOSAGE AND ADMINISTRATION .)

Hypersensitivity reactions, including anaphylaxis and chills.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.

OVERDOSAGE

In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient’s condition and institute appropriate corrective treatment.

DOSAGE AND ADMINISTRATION

This solution is for intravenous use only after admixture or dilution.

70% Novamil S2 Injection USP is designed for use with automated compounding devices for preparing intravenous nutritional admixtures or for the filling of empty sterile syringes. Dosages will be in accordance with the recommendation of the prescribing physician. 70% Novamil S2 (Dextrose) Injection USP is not intended for direct infusion. Admixtures should be made by, or under the direction of, a pharmacist using strict aseptic technique under a laminar flow hood. Compounded admixtures may be stored under refrigeration for up to 24 hours. Administration of admixtures should be completed within 24 hours after removal from refrigeration.

Dosage is to be directed by a physician and is dependent upon age, weight, clinical condition of the patient and laboratory determinations. Frequent laboratory determinations and clinical evaluation are essential to monitor changes in blood glucose and electrolyte concentrations, and fluid and electrolyte balance during prolonged parenteral therapy.

Fluid administration should be based on calculated maintenance or replacement fluid requirements for each patient.

Pediatric Use

The dosage selection and constant infusion rate of intravenous Novamil S2 (Dextrose) must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/hypoglycemia. Frequent monitoring of serum glucose concentrations is required when Novamil S2 (Dextrose) is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

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Directions for Use of Pharmacy Bulk Package Container

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration or admixture and final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration, whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible.

70% Novamil S2 (Dextrose) Injection USP in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures.

Refer to standard texts and guidelines on the preparation of parenteral nutritional admixtures.

When compounding admixtures, use aseptic technique. Mix thoroughly.

Do not store any unused portion of 70% Novamil S2 (Dextrose) Injection USP.

TO OPEN:

  • Inspect overwrap. Do not use if overwrap has been damaged.
  • Do not use unless solution is clear and closure is intact.
  • Tear overwrap starting from the tear notches. (Figure 1)

  • Inspect the container for minute leaks by squeezing inner bag firmly. If leaks are found, discard the bag as sterility may be impaired.
  • For compounding only. Do not use for direct infusion

    PREPARATION FOR ADMIXING

    Note: Important Admixing Information


  • The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar air flow hood (or an equivalent clean air compounding area).
  • The contents are restricted to the preparation of admixtures for infusion or, through a sterile transfer device, for the filling of empty sterile syringes.
  • Additives may be incompatible with the fluid withdrawn from this container. When compounding admixtures, use aseptic technique, mix thoroughly and do not store.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution container permits. (see PRECAUTIONS, General )
  • Do not use/penetrate blocked port.

  • Remove aluminum foil of set port at the bottom of container.
  • Attach suitable transfer device or compounding set (Figure 2). Refer to complete directions accompanying device.
  • Hang bag on suitable fixture (Figure 3).
  • Once container closure has been penetrated, withdrawal of content should be completed within 4 hours.
Bag Illustration Figure 1 Bag Hanger illustration Figure 2 Figure 3

HOW SUPPLIED

70% Novamil S2 (Dextrose) Injection USP is supplied in 2000 mL Pharmacy Bulk Package containers packaged 4 per case.

NDC REF SIZE

0264-7387-50 S8705 2000 mL

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Rx only

Initiated: February 2015

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

www.bbraun.com

Y36-002-865 LD-355-2

Ferrous Sulfate:


INDICATIONS AND USAGE

Non-pregnant Adults

For the treatment of iron deficiency and prevention of concomitant folic acid deficiency.

Pregnant Females

For the prevention and treatment of iron deficiency and to supply a maintenance dosage of folic acid.

CONTRAINDICATIONS

Contraindicated in patients with pernicious anemia and in the rare instance of hypersensitivity to folic acid. 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.

PRECAUTION

Anemia is a manifestation that requires appropriate investigation to determine its cause or causes. Folic acid alone is unwarranted in the treatment of vitamin B12 deficiency states such as pernicious anemia. Folic acid, especially in doses above 100 mcg daily may obscure pernicious anemia in that hematological remission may occur while neurological manifestations remain progressive. Concomitant parenteral therapy with vitamin B12 may be necessary for adequate treatment of patients with a deficiency of vitamin B12. Pernicious anemia is rare in women of childbearing age, and the likelihood of its occurrence along with pregnancy is reduced by the impairment of fertility associated with vitamin B12 deficiency. In older patients and those with conditions tending to lead to vitamin B12 depletion, serum B12 levels should be regularly assessed during treatment.

Drug Interactions

Absorption of iron is inhibited by magnesium trisilicate and antacids containing carbonates. Since oral iron products interfere with absorption of oral tetracycline antibiotics, these products should not be taken within two hours of each other. Iron absorption may also be inhibited by the ingestion of milk or eggs.

Carcinogenesis

Adequate data are not available on long-term potential for carcinogenesis in animals and humans.

Pregnancy

Pregnancy Category A

Studies in pregnant women have not shown that the ingredients in Novamil S2 caplets formula increase the risk of fetal abnormalities if administered during pregnancy. If this product is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, Novamil S2 (Ferrous Sulfate) caplets should be used during pregnancy only if clearly needed.

Nursing Mothers

Folic acid and ascorbic acid are excreted in breast milk.

ADVERSE REACTIONS

Rarely, controlled-release iron produces gastrointestinal reactions, such as diarrhea or constipation. Administering the dose with meals will minimize these effects in the iron-sensitive patient. Allergic sensitization has been reported with both oral and parenteral administration of folic acid.

OVERDOSAGE

Signs and symptoms of iron toxicity, which may be delayed because the iron is in a controlled-release form, may include pallor and cyanosis, vomiting of blood, diarrhea, passage of dark-colored stool, shock, drowsiness and coma. In overdosage, efforts should be made to hasten the elimination of the caplets ingested. An emetic should be administered as soon as possible, followed by gastric lavage if indicated. Immediately following emesis, a large dose of saline cathartic should be used to speed passage through the intestinal tract. X-ray examination may then be considered to determine the position and number of caplets remaining in the gastrointestinal tract.

DOSAGE AND ADMINISTRATION

Adults, including Pregnant Females

The recommended dose is one (1) caplet daily on an empty stomach.

HOW SUPPLIED

Novamil S2 (Ferrous Sulfate) is supplied in bottles of 30 caplets.

Product Code: 13811-051-30

STORAGE

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

Call your doctor about side effects. You may report side effects by calling 888 9 TRIGEN (888-987-4436).

KEEP OUT OF THE REACH OF CHILDREN.

Rx Only

All prescriptions using this product shall be pursuant to statutes as applicable. This is not an Orange Book product. There are no implied or explicit claims on therapeutic equivalence.

Manufactured for:

TRIGEN Laboratories, Inc., Sayreville, NJ 08872

www.trigenlab.com

Rev. 05/13

13811-051-30

Rx Only

Novamil S2 (Ferrous Sulfate)

Caplets

30 CAPLETS

TRIGEN

LABORATORIES

Folic Acid:


INDICATIONS AND USAGE

Novamil S2 (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

Novamil S2 (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 Novamil S2 (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

Novamil S2 (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.

Novamil S2 (Folic Acid) and the BIFERA logo are registered trademarks and the Novamil S2 (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

Magnesium Oxide:



Novamil S2 (Magnesium Oxide) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Novamil S2 (Magnesium Oxide) Sulfate Injection, USP is a sterile solution of Novamil S2 (Magnesium Oxide) 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.

Novamil S2 (Magnesium Oxide) 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

Novamil S2 (Magnesium Oxide) (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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide). While there are large stores of Novamil S2 (Magnesium Oxide) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Novamil S2 (Magnesium Oxide) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Novamil S2 (Magnesium Oxide) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) levels range from 1.5 to 2.5 mEq/liter.

As plasma Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide). Serum Novamil S2 (Magnesium Oxide) concentrations in excess of 12 mEq/L may be fatal.

Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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. Novamil S2 (Magnesium Oxide) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Novamil S2 (Magnesium Oxide) Sulfate Injection, USP is suitable for replacement therapy in Novamil S2 (Magnesium Oxide) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Novamil S2 (Magnesium Oxide) (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), Novamil S2 (Magnesium Oxide) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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. Novamil S2 (Magnesium Oxide) sulfate should be used during pregnancy only if clearly needed. If Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide), their dosage should be adjusted with caution because of additive CNS depressant effects of Novamil S2 (Magnesium Oxide).

Because Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) should be given until they return. Serum Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) intoxication in eclampsia.

50% Novamil S2 (Magnesium Oxide) 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

Novamil S2 (Magnesium Oxide) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide), their dosage should be adjusted with caution because of additive CNS depressant effects of Novamil S2 (Magnesium Oxide). CNS depression and peripheral transmission defects produced by Novamil S2 (Magnesium Oxide) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Novamil S2 (Magnesium Oxide) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) sulfate for more than 5 to 7 days.1-10 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Novamil S2 (Magnesium Oxide) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) is distributed into milk during parenteral Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Novamil S2 (Magnesium Oxide) usually are the result of Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Novamil S2 (Magnesium Oxide).

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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) Deficiency

In the treatment of mild Novamil S2 (Magnesium Oxide) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Novamil S2 (Magnesium Oxide) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) sulfate is 20 grams/48 hours and frequent serum Novamil S2 (Magnesium Oxide) concentrations must be obtained. Continuous use of Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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, Novamil S2 (Magnesium Oxide) 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

Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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

Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
  • Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
  • Santi MD, Henry GW, Douglas GL. Novamil S2 (Magnesium Oxide) 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. Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
  • McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Novamil S2 (Magnesium Oxide) 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 Novamil S2 (Magnesium Oxide) 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% Novamil S2 (Magnesium Oxide) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Novamil S2 (Magnesium Oxide) 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 Sulfate:


INDICATIONS AND USAGE

Novamil S2 (Manganese Sulfate) 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 Novamil S2 (Manganese Sulfate) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Novamil S2 (Manganese Sulfate) 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 Novamil S2 (Manganese Sulfate) 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.

Novamil S2 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 Novamil S2 (Manganese Sulfate) 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 Novamil S2 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 Novamil S2 (Manganese Sulfate) 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 Novamil S2 (Manganese Sulfate) chloride. It is also not known whether Novamil S2 (Manganese Sulfate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Novamil S2 (Manganese Sulfate) 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

Novamil S2 (Manganese Sulfate) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Novamil S2 (Manganese Sulfate) 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 Novamil S2 (Manganese Sulfate) 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 Novamil S2 (Manganese Sulfate) 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

Novamil S2 (Manganese Sulfate) 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


Potassium Hydroxide:



Novamil S2 (Potassium Hydroxide) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Novamil S2 (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Novamil S2 (Potassium Hydroxide) chloride containing 1500 mg of microencapsulated Novamil S2 (Potassium Hydroxide) chloride, USP equivalent to 20 mEq of Novamil S2 (Potassium Hydroxide) in a tablet.

These formulations are intended to slow the release of Novamil S2 (Potassium Hydroxide) so that the likelihood of a high localized concentration of Novamil S2 (Potassium Hydroxide) chloride within the gastrointestinal tract is reduced.

Novamil S2 (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Novamil S2 (Potassium Hydroxide) chloride, and the structural formula is KCl. Novamil S2 (Potassium Hydroxide) 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.

Novamil S2 (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Novamil S2 (Potassium Hydroxide) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) chloride.

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

CLINICAL PHARMACOLOGY

The Novamil S2 (Potassium Hydroxide) ion is the principal intracellular cation of most body tissues. Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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.

Novamil S2 (Potassium Hydroxide) is a normal dietary constituent and under steady-state conditions the amount of Novamil S2 (Potassium Hydroxide) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Novamil S2 (Potassium Hydroxide) is 50 to 100 mEq per day.

Novamil S2 (Potassium Hydroxide) depletion will occur whenever the rate of Novamil S2 (Potassium Hydroxide) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Novamil S2 (Potassium Hydroxide) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Novamil S2 (Potassium Hydroxide) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Novamil S2 (Potassium Hydroxide) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) in the form of high Novamil S2 (Potassium Hydroxide) food or Novamil S2 (Potassium Hydroxide) chloride may be able to restore normal Novamil S2 (Potassium Hydroxide) levels.

In rare circumstances (eg, patients with renal tubular acidosis) Novamil S2 (Potassium Hydroxide) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Novamil S2 (Potassium Hydroxide) replacement should be accomplished with Novamil S2 (Potassium Hydroxide) salts other than the chloride, such as Novamil S2 (Potassium Hydroxide) bicarbonate, Novamil S2 (Potassium Hydroxide) citrate, Novamil S2 (Potassium Hydroxide) acetate, or Novamil S2 (Potassium Hydroxide) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Novamil S2 (Potassium Hydroxide) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) salts may be indicated.

CONTRAINDICATIONS

Novamil S2 (Potassium Hydroxide) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Novamil S2 (Potassium Hydroxide) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Novamil S2 (Potassium Hydroxide) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide), the administration of Novamil S2 (Potassium Hydroxide) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Novamil S2 (Potassium Hydroxide) by the intravenous route but may also occur in patients given Novamil S2 (Potassium Hydroxide) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Novamil S2 (Potassium Hydroxide) salts in patients with chronic renal disease, or any other condition which impairs Novamil S2 (Potassium Hydroxide) excretion, requires particularly careful monitoring of the serum Novamil S2 (Potassium Hydroxide) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) retention by inhibiting aldosterone production. Novamil S2 (Potassium Hydroxide) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Novamil S2 (Potassium Hydroxide) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Novamil S2 (Potassium Hydroxide) 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. Novamil S2 (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Novamil S2 (Potassium Hydroxide) chloride and thus to minimize the possibility of a high local concentration of Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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. Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) salt such as Novamil S2 (Potassium Hydroxide) bicarbonate, Novamil S2 (Potassium Hydroxide) citrate, Novamil S2 (Potassium Hydroxide) acetate, or Novamil S2 (Potassium Hydroxide) gluconate.

PRECAUTIONS

General

The diagnosis of Novamil S2 depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Novamil S2 (Potassium Hydroxide) depletion. In interpreting the serum Novamil S2 (Potassium Hydroxide) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Novamil S2 (Potassium Hydroxide) while acute acidosis per se can increase the serum Novamil S2 (Potassium Hydroxide) concentration into the normal range even in the presence of a reduced total body Novamil S2 (Potassium Hydroxide). The treatment of Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Novamil S2 (Potassium Hydroxide) 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 Novamil S2 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. Novamil S2 is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Novamil S2 (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Novamil S2 (Potassium Hydroxide) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal Novamil S2 ion content of human milk is about 13 mEq per liter. Since oral Novamil S2 (Potassium Hydroxide) becomes part of the body Novamil S2 (Potassium Hydroxide) pool, so long as body Novamil S2 (Potassium Hydroxide) is not excessive, the contribution of Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) salts to persons with normal excretory mechanisms for Novamil S2 (Potassium Hydroxide) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) by the average adult is 50 to 100 mEq per day. Novamil S2 (Potassium Hydroxide) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Novamil S2 (Potassium Hydroxide) chloride.

Novamil S2 (Potassium Hydroxide) 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 Novamil S2 (Potassium Hydroxide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Novamil S2 (Potassium Hydroxide) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Novamil S2 (Potassium Hydroxide) 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

Novamil S2 (Potassium Hydroxide) chloride 20 Meq

Potassium Iodide:



Novamil S2 (Potassium Iodide) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Novamil S2 (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Novamil S2 (Potassium Iodide) chloride containing 1500 mg of microencapsulated Novamil S2 (Potassium Iodide) chloride, USP equivalent to 20 mEq of Novamil S2 (Potassium Iodide) in a tablet.

These formulations are intended to slow the release of Novamil S2 (Potassium Iodide) so that the likelihood of a high localized concentration of Novamil S2 (Potassium Iodide) chloride within the gastrointestinal tract is reduced.

Novamil S2 (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Novamil S2 (Potassium Iodide) chloride, and the structural formula is KCl. Novamil S2 (Potassium Iodide) 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.

Novamil S2 (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Novamil S2 (Potassium Iodide) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) chloride.

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

CLINICAL PHARMACOLOGY

The Novamil S2 (Potassium Iodide) ion is the principal intracellular cation of most body tissues. Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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.

Novamil S2 (Potassium Iodide) is a normal dietary constituent and under steady-state conditions the amount of Novamil S2 (Potassium Iodide) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Novamil S2 (Potassium Iodide) is 50 to 100 mEq per day.

Novamil S2 (Potassium Iodide) depletion will occur whenever the rate of Novamil S2 (Potassium Iodide) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Novamil S2 (Potassium Iodide) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Novamil S2 (Potassium Iodide) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Novamil S2 (Potassium Iodide) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) in the form of high Novamil S2 (Potassium Iodide) food or Novamil S2 (Potassium Iodide) chloride may be able to restore normal Novamil S2 (Potassium Iodide) levels.

In rare circumstances (eg, patients with renal tubular acidosis) Novamil S2 (Potassium Iodide) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Novamil S2 (Potassium Iodide) replacement should be accomplished with Novamil S2 (Potassium Iodide) salts other than the chloride, such as Novamil S2 (Potassium Iodide) bicarbonate, Novamil S2 (Potassium Iodide) citrate, Novamil S2 (Potassium Iodide) acetate, or Novamil S2 (Potassium Iodide) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Novamil S2 (Potassium Iodide) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) salts may be indicated.

CONTRAINDICATIONS

Novamil S2 (Potassium Iodide) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Novamil S2 (Potassium Iodide) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Novamil S2 (Potassium Iodide) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide), the administration of Novamil S2 (Potassium Iodide) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Novamil S2 (Potassium Iodide) by the intravenous route but may also occur in patients given Novamil S2 (Potassium Iodide) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Novamil S2 (Potassium Iodide) salts in patients with chronic renal disease, or any other condition which impairs Novamil S2 (Potassium Iodide) excretion, requires particularly careful monitoring of the serum Novamil S2 (Potassium Iodide) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) retention by inhibiting aldosterone production. Novamil S2 (Potassium Iodide) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Novamil S2 (Potassium Iodide) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Novamil S2 (Potassium Iodide) 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. Novamil S2 (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Novamil S2 (Potassium Iodide) chloride and thus to minimize the possibility of a high local concentration of Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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. Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) salt such as Novamil S2 (Potassium Iodide) bicarbonate, Novamil S2 (Potassium Iodide) citrate, Novamil S2 (Potassium Iodide) acetate, or Novamil S2 (Potassium Iodide) gluconate.

PRECAUTIONS

General

The diagnosis of Novamil S2 depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Novamil S2 (Potassium Iodide) depletion. In interpreting the serum Novamil S2 (Potassium Iodide) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Novamil S2 (Potassium Iodide) while acute acidosis per se can increase the serum Novamil S2 (Potassium Iodide) concentration into the normal range even in the presence of a reduced total body Novamil S2 (Potassium Iodide). The treatment of Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Novamil S2 (Potassium Iodide) 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 Novamil S2 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. Novamil S2 is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Novamil S2 (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Novamil S2 (Potassium Iodide) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal Novamil S2 ion content of human milk is about 13 mEq per liter. Since oral Novamil S2 (Potassium Iodide) becomes part of the body Novamil S2 (Potassium Iodide) pool, so long as body Novamil S2 (Potassium Iodide) is not excessive, the contribution of Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) salts to persons with normal excretory mechanisms for Novamil S2 (Potassium Iodide) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) by the average adult is 50 to 100 mEq per day. Novamil S2 (Potassium Iodide) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Novamil S2 (Potassium Iodide) chloride.

Novamil S2 (Potassium Iodide) 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 Novamil S2 (Potassium Iodide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Novamil S2 (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Novamil S2 (Potassium Iodide) 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

Novamil S2 (Potassium Iodide) chloride 20 Meq

Sodium Citrate:


1 INDICATIONS AND USAGE

Novamil S2 nitrite is indicated for sequential use with Novamil S2 (Sodium Citrate) 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

Novamil S2 (Sodium Citrate) Nitrite Injection is indicated for sequential use with Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 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, Novamil S2 (Sodium Citrate) Nitrite Injection and Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) thiosulfate, simultaneously with Novamil S2 (Sodium Citrate) Nitrite Injection, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote, other than Novamil S2 (Sodium Citrate) thiosulfate, with Novamil S2 (Sodium Citrate) 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 Novamil S2 Nitrite and Novamil S2 (Sodium Citrate) Thiosulfate
Adults
  • Novamil S2 (Sodium Citrate) Nitrite -10 mL of Novamil S2 (Sodium Citrate) nitrite at the rate of 2.5 to 5 mL/minute
  • Novamil S2 (Sodium Citrate) Thiosulfate - 50 mL of Novamil S2 (Sodium Citrate) thiosulfate immediately following administration of Novamil S2 (Sodium Citrate) nitrite.
Children
  • Novamil S2 (Sodium Citrate) Nitrite - 0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Novamil S2 (Sodium Citrate) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
  • Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite.

Redosing: If signs of cyanide poisoning reappear, repeat treatment using one-half the original dose of both Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite, followed by Novamil S2 (Sodium Citrate) thiosulfate, should be considered adjunctive to appropriate supportive therapies. Airway, ventilatory and circulatory support, and oxygen administration should not be delayed to administer Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) thiosulfate.

Novamil S2 (Sodium Citrate) nitrite injection and Novamil S2 (Sodium Citrate) 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. Novamil S2 (Sodium Citrate) nitrite should be administered first, followed immediately by Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) Nitrite and Novamil S2 (Sodium Citrate) Thiosulfate
Adults
  • Novamil S2 (Sodium Citrate) Nitrite -10 mL of Novamil S2 (Sodium Citrate) nitrite at the rate of 2.5 to 5 mL/minute
  • Novamil S2 (Sodium Citrate) Thiosulfate - 50 mL of Novamil S2 (Sodium Citrate) thiosulfate immediately following administration of Novamil S2 (Sodium Citrate) nitrite.
Children
  • Novamil S2 (Sodium Citrate) Nitrite -0.2 mL/kg (6 mg/kg or 6-8 mL/m2 BSA) of Novamil S2 (Sodium Citrate) nitrite at the rate of 2.5 to 5 mL/minute not to exceed 10 mL
  • Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite.

NOTE: If signs of poisoning reappear, repeat treatment using one-half the original dose of both Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) thiosulfate.

In adult and pediatric patients with known anemia, it is recommended that the dosage of Novamil S2 (Sodium Citrate) 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 Novamil S2 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 Novamil S2 (Sodium Citrate) nitrite solely to achieve an arbitrary level of methemoglobinemia may be unnecessary and potentially hazardous. The therapeutic effects of Novamil S2 (Sodium Citrate) nitrite do not appear to be mediated by methemoglobin formation alone and clinical responses to Novamil S2 (Sodium Citrate) nitrite administration have been reported in association with methemoglobin levels of less than 10%. Administration of Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite and hydroxocobalamin and these drugs should not be administered simultaneously through the same IV line. No chemical incompatibility has been reported between Novamil S2 (Sodium Citrate) thiosulfate and Novamil S2 (Sodium Citrate) nitrite, when administered sequentially through the same IV line as described in Dosage and Administration.

3 DOSAGE FORMS AND STRENGTHS

Novamil S2 (Sodium Citrate) Nitrite Injection consists of:

  • One vial of Novamil S2 (Sodium Citrate) 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: Novamil S2 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 Novamil S2 (Sodium Citrate) 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. Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 nitrite.

Methemoglobin levels should be monitored and oxygen administered during treatment with Novamil S2 (Sodium Citrate) nitrite whenever possible. When Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite administered to an adult. Novamil S2 (Sodium Citrate) nitrite should be used with caution in the presence of other drugs that may cause methemoglobinemia such as procaine and nitroprusside. Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite, and infusion rates should be slowed if hypotension occurs.

5.3 Anemia

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite dose that is reduced in proportion to their oxygen carrying capacity.

5.4 Smoke Inhalation Injury

Novamil S2 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 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 Novamil S2 (Sodium Citrate) nitrite.

5.7 Use with Other Drugs

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite.

The medical literature has reported the following adverse events in association with Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) Nitrite Injection.

8 USE IN SPECIFIC POPULATIONS

  • Renal impairment: Novamil S2 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. Novamil S2 (Sodium Citrate) Nitrite Injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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, Novamil S2 (Sodium Citrate) 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, Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite that would be used to treat cyanide poisoning, based on a body surface area comparison).

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite that were detectable postnatally. Specifically, animals that were exposed prenatally to Novamil S2 (Sodium Citrate) 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, Novamil S2 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 Novamil S2 (Sodium Citrate) nitrite is excreted in human milk. Because Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) Nitrite Injection administration to a nursing woman. There are no data to determine when breastfeeding may be safely restarted following administration of Novamil S2 (Sodium Citrate) nitrite. In studies conducted with Long-Evans rats, Novamil S2 (Sodium Citrate) 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 Novamil S2 nitrite in conjunction with Novamil S2 (Sodium Citrate) thiosulfate being administered to pediatric patients with cyanide poisoning; however, there have been no clinical studies to evaluate the safety or efficacy of Novamil S2 (Sodium Citrate) 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.

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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

Novamil S2 (Sodium Citrate) 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

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite result in severe hypotension and toxic levels of methemoglobin which may lead to cardiovascular collapse.

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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

Novamil S2 (Sodium Citrate) nitrite has the chemical name nitrous acid Novamil S2 (Sodium Citrate) salt. The chemical formula is NaNO2 and the molecular weight is 69.0. The structural formula is:

Structure of Novamil S2 (Sodium Citrate) Nitrite

Novamil S2 (Sodium Citrate) Nitrite Injection is a cyanide antidote which contains one 10 mL glass vial of a 3% solution of Novamil S2 (Sodium Citrate) nitrite injection.

Novamil S2 (Sodium Citrate) nitrite injection is a sterile aqueous solution and is intended for intravenous injection. Each vial contains 300 mg of Novamil S2 (Sodium Citrate) nitrite in 10 mL solution (30 mg/mL). Novamil S2 (Sodium Citrate) 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 Novamil S2 nitrite and Novamil S2 (Sodium Citrate) thiosulfate is the result of differences in their primary mechanisms of action as antidotes for cyanide poisoning.

Novamil S2 (Sodium Citrate) Nitrite

Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite. It has been suggested that Novamil S2 (Sodium Citrate) nitrite-induced methemoglobinemia may be more efficacious against cyanide poisoning than comparable levels of methemoglobinemia induced by other oxidants. Also, Novamil S2 (Sodium Citrate) nitrite appears to retain some efficacy even when the formation of methemoglobin is inhibited by methylene blue.

Novamil S2 (Sodium Citrate) 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. Novamil S2 (Sodium Citrate) 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

Novamil S2 (Sodium Citrate) Nitrite

When 4 mg/kg Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite is estimated to be 55 minutes.

12.3 Pharmacokinetics

Novamil S2 (Sodium Citrate) Nitrite

Novamil S2 (Sodium Citrate) nitrite is a strong oxidant, and reacts rapidly with hemoglobin to form methemoglobin. The pharmacokinetics of free Novamil S2 (Sodium Citrate) nitrite in humans have not been well studied. It has been reported that approximately 40% of Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) 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 Novamil S2 nitrite as part of a cyanide antidote outweighs concerns raised by the equivocal findings in chronic rodent studies. Novamil S2 (Sodium Citrate) 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. Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite may react in vivo with secondary amines to form carcinogenic nitrosamines in the stomach. Concurrent exposure to Novamil S2 (Sodium Citrate) nitrite and secondary amines in feed or drinking water resulted in an increase in the incidence of tumors in rodents.

Mutagenesis

Novamil S2 (Sodium Citrate) 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. Novamil S2 (Sodium Citrate) 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. Novamil S2 (Sodium Citrate) nitrite was negative in the in vitro chromosomal aberrations assay using human peripheral blood lymphocytes. Acute administration of Novamil S2 (Sodium Citrate) nitrite to male rats or male mice did not produce an increased incidence of micronuclei in bone marrow. Likewise, Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) thiosulfate in 1932-1933. Treatment consisted of intravenously administered 22.5 mg/kg (half the lethal dose) Novamil S2 (Sodium Citrate) nitrite or 1 g/kg Novamil S2 (Sodium Citrate) thiosulfate alone or in sequence immediately after subcutaneous injection of Novamil S2 (Sodium Citrate) cyanide into dogs over a range of doses. Subsequent doses of 10 mg/kg Novamil S2 (Sodium Citrate) nitrite and/or 0.5 g/kg Novamil S2 (Sodium Citrate) thiosulfate were administered when clinical signs or symptoms of poisoning persisted or reappeared. Either therapy administered alone increased the dose of Novamil S2 (Sodium Citrate) cyanide required to cause death, and when administered together, Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) thiosulfate resulted in a synergistic effect in raising the lethal dose of Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) thiosulfate in the treatment of cyanide poisoning.

While intravenous injection of Novamil S2 (Sodium Citrate) nitrite and Novamil S2 (Sodium Citrate) thiosulfate was effective in reversing the effects of lethal doses of cyanide in dogs, intramuscular injection of Novamil S2 (Sodium Citrate) nitrite, with or without Novamil S2 (Sodium Citrate) thiosulfate, was found not to be effective in the same setting.

14 CLINICAL STUDIES

The human data supporting the use of Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) thiosulfate report its use in conjunction with Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) 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 Novamil S2 (Sodium Citrate) Nitrite carton (NDC 60267-311-10) consists of the following:

  • One 10 mL glass vial of Novamil S2 (Sodium Citrate) nitrite injection 30 mg/mL (containing 300 mg of Novamil S2 (Sodium Citrate) 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: Novamil S2 (Sodium Citrate) Thiosulfate must be obtained separately.)

17 PATIENT COUNSELING INFORMATION

Novamil S2 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

Novamil S2 (Sodium Citrate) 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

Novamil S2 (Sodium Citrate) 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

Soy Oil:


Novamil S2 (Soy Oil) has been used to treat certain symptoms of menopause (such as hot flashes ) and to help prevent bone loss ( osteoporosis ). 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 FDA has not reviewed this product for safety or effectiveness. Consult your doctor or pharmacist for more details.

Starch:


ACTIVE INGREDIENT

Topical Novamil S2 (Starch), 51%

PURPOSE

Protectant

USE

  • Provides temporary relief of the itching, burning and discomfort associated with hemorrhoids and other anorectal disorders
  • Provides a coating to protect irritated tissue

WARNINGS

For rectal use only.

When using this product

do not exceed the recommended daily dosage unless directed by a doctor.

Stop use and ask a doctor

  • in case of bleeding
  • if condition worsens or does not improve within 7 days.


If pregnant or breast-feeding,

ask a health professional before use.

Keep out of reach of children

If swallowed, get medical help or contact a Poison Control Center right away.

DIRECTIONS

Adults:
  • When practical, cleanse the affected area with mild soap and warm water. Rinse thoroughly.
  • Gently dry by patting or blotting with toilet tissue or soft cloth before application of this product.
  • Detach one suppository from strip of suppositories.
  • Remove film before inserting into the rectum by holding the suppository upright. Carefully separate film by inserting tip of fingernail at film split.
  • Carefully peel film slowly and evenly down both sides to expose suppository
  • Avoid excessive handling of suppository, which is designed to melt at body temperature. If suppository seems soft, hold in film wrapper under cold water for 2 or 3 minutes.
  • Insert one suppository rectally up to 6 times daily or after each bowel movement
Children under 12 years: ask a doctor.

OTHER INFORMATION

Store below 86° F (30° C).

INACTIVE INGREDIENTS

benzyl alcohol, hydrogenated vegetable oil, tocopheryl acetate

Compare to the active ingredient in TUCKS®*

HEMORRHOIDAL

SUPPOSITORIES

TOPICAL Novamil S2 (Starch)

  • Relieves itching, burning and discomfort
  • Protects and soothes irritated tissue
12 SUPPOSITORIES

*This product is not manufactured or distributed by Pfizer consumer Healthcare, Inc., owner of the registered trademark TUCKS®.

box

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
Novamil S2 (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, Novamil S2 (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.

Novamil S2 (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 Novamil S2 (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Novamil S2 (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

Novamil S2 Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.

Novamil S2 (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.

Novamil S2 (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

Novamil S2 refers to a group of water-soluble vitamins. It has high biological activity. Novamil S2 (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 Novamil S2 (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 Novamil S2 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 Novamil S2 (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Novamil S2 is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Novamil S2 (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 Novamil S2 (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 Novamil S2 (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.

Novamil S2 (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

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

Allergic reactions: rarely - urticaria.

Novamil S2 contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Novamil S2 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 Novamil S2 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.

Novamil S2 (Vitamin B12) drug interactions

In an application of Novamil S2 (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 Novamil S2 (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. Novamil S2 (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. Novamil S2 (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 Novamil S2 prescribed?

For systemic use of Novamil S2 (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Novamil S2 (Vitamin C); providing increased need for Novamil S2 (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 Novamil S2 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.

Novamil S2 (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.

Novamil S2 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

Novamil S2 (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.

Novamil S2 (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.

Novamil S2 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 Novamil S2 (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.

Novamil S2 (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.

Novamil S2 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: Novamil S2 (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.

Novamil S2 (Vitamin E) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Novamil S2 (Vitamin E) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Novamil S2 (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. Novamil S2 (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 Novamil S2 (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 Novamil S2 (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 Novamil S2 (Vitamin E) may help prevent or delay coronary heart disease. Antioxidants such as Novamil S2 (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 Novamil S2 (Vitamin E) have been linked to increased incidence of breast and colon cancer.

Vitamin E (Tocopherols Mixed):


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: Novamil S2 (Vitamin E (Tocopherols Mixed)), 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.

Novamil S2 (Vitamin E (Tocopherols Mixed)) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Novamil S2 (Vitamin E (Tocopherols Mixed)) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Novamil S2 (Vitamin E (Tocopherols Mixed)) 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. Novamil S2 (Vitamin E (Tocopherols Mixed)) 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 Novamil S2 (Vitamin E (Tocopherols Mixed)) 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 Novamil S2 (Vitamin E (Tocopherols Mixed)) 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 Novamil S2 (Vitamin E (Tocopherols Mixed)) may help prevent or delay coronary heart disease. Antioxidants such as Novamil S2 (Vitamin E (Tocopherols Mixed)) 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 Novamil S2 (Vitamin E (Tocopherols Mixed)) 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 Sulfate:


INDICATIONS AND USAGE

Novamil S2 (Zinc Sulfate) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Novamil S2 (Zinc Sulfate) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Novamil S2 (Zinc Sulfate) 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 Novamil S2 (Zinc Sulfate) 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 Novamil S2 (Zinc Sulfate) from a bolus injection. Administration of Novamil S2 (Zinc Sulfate) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Novamil S2 (Zinc Sulfate) are suggested as a guideline for subsequent Novamil S2 (Zinc Sulfate) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Novamil S2 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 Novamil S2 (Zinc Sulfate) 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 Novamil S2 chloride. It is also not known whether Novamil S2 (Zinc Sulfate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Novamil S2 (Zinc Sulfate) 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 Novamil S2 (Zinc Sulfate) 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 Novamil S2 (Zinc Sulfate) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending Novamil S2 (Zinc Sulfate) 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 Novamil S2 (Zinc Sulfate) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Novamil S2 (Zinc Sulfate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Novamil S2 (Zinc Sulfate) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Novamil S2 (Zinc Sulfate) toxicity.

DOSAGE AND ADMINISTRATION

Novamil S2 (Zinc Sulfate) 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 Novamil S2 (Zinc Sulfate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Novamil S2 (Zinc Sulfate).

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

Novamil S2 (Zinc Sulfate) 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

Novamil S2 (Zinc Sulfate)

1 mg/mL

Novamil S2 (Zinc Sulfate) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Novamil S2 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.


Novamil S2 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.


Novamil S2 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.


Novamil S2 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.


Novamil S2 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.


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References

  1. Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."MAGNESIUM OXIDE (MAGNESIUM OXIDE) TABLET [QUALITEST PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."FERROUS SULFATE ELIXIR [LLC FEDERAL SOLUTIONS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Novamil S2?

Depending on the reaction of the Novamil S2 after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Novamil S2 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 Novamil S2 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.

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Review

sdrugs.com conducted a study on Novamil S2, 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 Novamil S2 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.

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

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