Vitrimix

Calcium (Calcium Chloride):

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Vitrimix (Calcium (Calcium Chloride)) reviews

1 INDICATIONS AND USAGE

Vitrimix (Calcium (Calcium Chloride)) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

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

2 DOSAGE AND ADMINISTRATION

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

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

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

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg Vitrimix (Calcium (Calcium Chloride)) acetate capsule.

- Capsule: 667 mg Vitrimix (Calcium (Calcium Chloride)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Vitrimix ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Vitrimix (Calcium (Calcium Chloride)) acetate. (5.1)

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

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

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

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

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

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

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

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

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

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

- In clinical studies, patients have occasionally experienced nausea during Vitrimix (Calcium (Calcium Chloride)) acetate therapy. (6)

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

6.1 Clinical Trial Experience

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

In clinical studies, Vitrimix (Calcium (Calcium Chloride)) acetate has been generally well tolerated.

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

Preferred Term	Total adverse reactions reported for Vitrimix (Calcium (Calcium Chloride)) acetate N=167 N (%)	3 month, open label study of Vitrimix (Calcium (Calcium Chloride)) acetate N=98 N (%)	Double blind, placebo-controlled, cross-over study of liquid Vitrimix (Calcium (Calcium Chloride)) acetate N=69
			Vitrimix (Calcium (Calcium Chloride)) acetate N (%)	Placebo N (%)
Nausea	6 (3.6)	6 (6.1)	0 (0)	0 (0)
Vomiting	4 (2.4)	4 (4.1)	0 (0)	0 (0)
Hypercalcemia	21 (12.6)	16 (16.3)	5 (7.2)	0 (0)

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

6.2 Postmarketing Experience

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

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

7 DRUG INTERACTIONS

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

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

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

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

7.1 Ciprofloxacin

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Vitrimix (Calcium (Calcium Chloride)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

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

10 OVERDOSAGE

Administration of Vitrimix (Calcium (Calcium Chloride)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

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

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

Vitrimix (Calcium (Calcium Chloride)) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

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

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Vitrimix (Calcium (Calcium Chloride)) acetate.

14 CLINICAL STUDIES

Effectiveness of Vitrimix (Calcium (Calcium Chloride)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Vitrimix (Calcium (Calcium Chloride)) acetate solid oral dosage form.

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

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

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

* Ninety-one patients completed at least 6 weeks of the study. † ANOVA of difference in values at pre-study and study completion. ‡ Values expressed as mean ± SE.
Parameter	Pre-Study	Week 4*	Week 8	Week 12	p-value†
Phosphorus (mg/dL)‡	7.4 ± 0.17	5.9 ± 0.16	5.6 ± 0.17	5.2 ± 0.17	≤0.01
Vitrimix (Calcium (Calcium Chloride)) (mg/dL)‡	8.9 ± 0.09	9.5 ± 0.10	9.7 ± 0.10	9.7 ± 0.10	≤0.01

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

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

The phosphate binding effect of Vitrimix (Calcium (Calcium Chloride)) acetate is shown in the Table 3.

* ANOVA of Vitrimix (Calcium (Calcium Chloride)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM.
Parameter	Pre-Study	Post-Treatment		p-value*
		Vitrimix (Calcium (Calcium Chloride)) Acetate	Placebo
Phosphorus (mg/dL)†	7.3 ± 0.18	5.9 ± 0.24	7.8 ± 0.22	<0.01
Vitrimix (Calcium (Calcium Chloride)) (mg/dL)†	8.9 ± 0.11	9.5 ± 0.13	8.8 ± 0.12	<0.01

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

16 HOW SUPPLIED/STORAGE AND HANDLING

Vitrimix (Calcium (Calcium Chloride)) Acetate Capsules

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

NDC 0615-2303-39: Blistercards of 30 Capsules

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

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

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

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

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Dextrose:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• Directions for use of pharmacy bulk package container
• How supplied
• Vitrimix (Dextrose) reviews

INDICATIONS AND USAGE

70% Vitrimix (Dextrose) Injection USP is indicated as a caloric component in a parenteral nutrition regimen. 70% Vitrimix (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% Vitrimix (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 Vitrimix (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 Vitrimix (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% Vitrimix (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% Vitrimix (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% Vitrimix (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 Vitrimix (Dextrose) in water may increase the volume of extracellular fluid and cause water intoxication.

Solutions containing Vitrimix (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 Vitrimix (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 Vitrimix (Dextrose) injection may result in increased serum osmolality and possible intracerebral hemorrhage.

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 Vitrimix 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 Vitrimix (Dextrose) solutions. Sufficient amounts of potassium should be added to Vitrimix (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% Vitrimix (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 Vitrimix (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% Vitrimix (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% Vitrimix 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 Vitrimix (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 Vitrimix Injections, USP in pregnant women and animal reproduction studies have not been conducted with this drug. Therefore, it is not known whether Vitrimix (Dextrose) Injections USP can cause fetal harm when administered to a pregnant woman. Vitrimix (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 Vitrimix (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 Vitrimix Injections USP are administered to a nursing woman.

Pediatric Use

The use of Vitrimix (Dextrose) in pediatric patients is based on clinical practice (see DOSAGE AND ADMINISTRATION ). Because of their hypertonicity, 70% Vitrimix (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 .

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 Vitrimix (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% Vitrimix 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% Vitrimix (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 Vitrimix (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 Vitrimix (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.

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% Vitrimix (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% Vitrimix (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% Vitrimix (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

Glycine:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Im-1453
• Vitrimix (Glycine) reviews

INDICATIONS AND USAGE

1.5% Vitrimix (Glycine) Irrigation, USP is indicated for use as irrigating fluid during transurethral prostatic resection and other transurethral surgical procedures.

CONTRAINDICATIONS

NOT FOR INJECTION BY USUAL PARENTERAL ROUTES.

Do not use in patients with anuria.

WARNINGS

FOR UROLOGIC IRRIGATION ONLY.

Solutions for urologic irrigation must be used with caution in patients with severe cardiopulmonary or renal dysfunction. Irrigating fluids used during transurethral prostatectomy have been demonstrated to enter the systemic circulation in relatively large volumes. Thus, Vitrimix (Glycine) irrigating solution must be regarded as a systemic drug. Absorption of large amounts of fluids containing Vitrimix (Glycine) may significantly alter cardiopulmonary and renal dynamics.

Do not heat container over 66°C (150°F).

PRECAUTIONS

Cardiovascular status, especially of the patient with cardiac disease, should be carefully observed before and during transurethral resection of the prostate when using Vitrimix (Glycine) irrigating solution, because the quantity of fluid absorbed into the systemic circulation by opened prostatic veins may produce significant expansion of the extracellular fluid and lead to fulminating congestive heart failure. Shift of sodium free intracellular fluid into the extracellular compartment following systemic absorption of solution may lower serum sodium concentration and aggravate pre-existing hyponatremia.

Care should be exercised if impaired liver function is known or suspected. Under such conditions, ammonia resulting from metabolism of Vitrimix (Glycine) may accumulate in the blood.

Aseptic technique is essential with the use of sterile solutions for irrigation. The administration set should be attached promptly. Unused portions should be discarded and a fresh container of appropriate size used for the start-up of each cycle or repeat procedure.

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

Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies with Vitrimix (Glycine) Irrigation, USP have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Nursing Mothers: Caution should be exercised when Vitrimix (Glycine) Irrigation, USP is administered to a nursing woman.

Pregnancy: Teratogenic Effects.

Pregnancy Category C. Animal reproduction studies have not been conducted with Vitrimix (Glycine) Irrigation, USP. It is also not known whether Vitrimix (Glycine) Irrigation, USP can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Vitrimix (Glycine) Irrigation, USP should be given to a pregnant woman only if clearly needed.

Pediatric Use: The safety and effectiveness of Vitrimix (Glycine) Irrigation have not been established. Its limited use in pediatric patients has been inadequate to fully define proper dosage and limitations for use.

ADVERSE REACTIONS

Adverse reactions may result from intravascular absorption of Vitrimix (Glycine). Large intravenous doses of Vitrimix (Glycine) are known to cause salivation, nausea and lightheadedness. Other consequences of absorption of urologic irrigating solutions include fluid and electrolyte disturbances such as acidosis, electrolyte loss, marked diuresis, urinary retention, edema, dryness of mouth, thirst, dehydration, coma from hyponatremia, secondary hyponatremia due to fluid overload, and hyper- ammonemia with resultant coma and/or encephalopathy; cardiovascular disorders such as hypotension, tachycardia, angina-like pains; pulmonary disorders such as pulmonary congestion; and other general reactions such as blurred vision, convulsions, nausea, vomiting, rhinitis, chills, vertigo, backache, transient blindness and urticaria. Allergic reactions from Vitrimix (Glycine) are unknown or exceedingly rare.

Should any adverse reaction occur, discontinue the irrigant, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.

DOSAGE AND ADMINISTRATION

1.5% Vitrimix (Glycine) Irrigation, USP should be administered only by transurethral instillation with appropriate urologic instrumentation. A disposable irrigation set should be used. The total volume of solution used for irrigation is solely at the discretion of the surgeon.

Height of container(s) above the operating table in excess of 60 cm (approx. 2 ft.) has been reported to increase intravascular absorption of the irrigating fluid.

Drug Interactions

Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, 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.

HOW SUPPLIED

1.5% Vitrimix (Glycine) Irrigation, USP is supplied in single-dose 3000 mL flexible irrigation container ( List No. 7974).

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. Store at 20 to 25°C (68 to 77°F).

Revised: October 2004

©Hospira 2004 EN-0577 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

IM-1453

iv bag ndc 0409-7974-08

2

HDPE

TO OPEN TEAR AT NOTCH

DO NOT REMOVE FROM OVERWRAP UNTIL READY FOR USE. AFTER REMOVING

THE OVERWRAP, CHECK FOR MINUTE LEAKS BY SQUEEZING CONTAINER FIRMLY.

IF LEAKS ARE FOUND, DISCARD SOLUTION AS STERILITY MAY BE IMPAIRED.

RECOMMENDED STORAGE: ROOM TEMPERATURE (25°C). AVOID EXCESSIVE

HEAT. PROTECT FROM FREEZING. SEE INSERT.

98-4321-R14-3/98

L-Alanine:

• Vitrimix (L-Alanine) reviews

A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system.

Indication: Used for protein synthesis.

Is an important source of energy for muscle tissue, the brain and central nervous system; strengthens the immune system by producing antibodies; helps in the metabolism of sugars and organic acids.

L-Arginine:

• Vitrimix (L-Arginine) reviews

An essential amino acid that is physiologically active in the L-form.

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

Studies have shown that is has improved immune responses to bacteria, viruses and tumor cells; promotes wound healing and regeneration of the liver; causes the release of growth hormones; considered crucial for optimal muscle growth and tissue repair.

L-Aspartic Acid:

• Vitrimix (L-Aspartic Acid) reviews

One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.

Indication: There is no support for the claim that aspartates are exercise performance enhancers, i.e. ergogenic aids.

L-aspartate is considered a non-essential amino acid, meaning that, under normal physiological conditions, sufficient amounts of the amino acid are synthesized in the body to meet the body's requirements. L-aspartate is formed by the transamination of the Krebs cycle intermediate oxaloacetate. The amino acid serves as a precursor for synthesis of proteins, oligopeptides, purines, pyrimidines, nucleic acids and L-arginine. L-aspartate is a glycogenic amino acid, and it can also promote energy production via its metabolism in the Krebs cycle. These latter activities were the rationale for the claim that supplemental aspartate has an anti-fatigue effect on skeletal muscle, a claim that was never confirmed.

L-Cysteine:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Dosage and administration
• Directions for proper use of pharmacy bulk package
• Recommended storage conditions after opening
• How supplied
• Vitrimix (L-Cysteine) reviews

INDICATIONS AND USAGE

Vitrimix (L-Cysteine) Hydrochloride Injection, USP is intended for use only after dilution as an additive to Crystalline Amino Acid Injections to meet the intravenous amino acid nutritional requirements of infants receiving total parenteral nutrition.

CONTRAINDICATIONS

This preparation should not be used in patients with hepatic coma or metabolic disorders involving impaired nitrogen utilization.

WARNINGS

Peripheral intravenous infusion of amino acids may induce a rise in blood urea nitrogen (BUN) especially in patients with impaired hepatic or renal function. Appropriate laboratory tests should be performed periodically and infusion discontinued if BUN levels exceed normal postprandial limits and continue to rise. It should be noted that a modest rise in BUN normally occurs as a result of increased protein intake.

Administration of amino acid solutions to a patient with hepatic insufficiency may result in serum amino acid imbalances, metabolic alkalosis, prerenal azotemia, hyperammonemia, stupor and coma.

Administration of amino acid solutions in the presence of impaired renal function may augment an increasing BUN, as does any protein dietary component.

Solutions containing sodium ion should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency, and in clinical states in which there exists edema with sodium retention.

Solutions which contain potassium ion should be used with great care, if at all, in patients with hyperkalemia, severe renal failure and in conditions in which potassium retention is present.

Solutions containing acetate ion should be used with great care in patients with metabolic or respiratory alkalosis. Acetate should be administered with great care in those conditions in which there is an increased level or an impaired utilization of this ion such as severe hepatic insufficiency.

Hyperammonemia is of special significance in infants, as it can result in mental retardation. Therefore it is essential that blood ammonia levels be measured frequently in infants.

Instances of asymptomatic hyperammonemia have been reported in patients without overt liver dysfunction. The mechanisms of this reaction are not clearly defined but may involve genetic defects and immature or subclinically impaired liver function.

Frequent Clinical Evaluation and Laboratory Determinations are Necessary for Proper Monitoring During Administration. Blood studies should include glucose, urea nitrogen, serum electrolytes, ammonia, cholesterol, acid-base balance, serum proteins, kidney and liver function tests, osmolarity and hemogram. White blood count and blood cultures are to be determined if indicated. Urinary osmolarity and glucose should be determined frequently.

Safe use during pregnancy has not been established, therefore, infusion of amino acids should be undertaken during pregnancy only when this is deemed essential to the patients' welfare, as judged by the physician.

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

Special care must be taken when administering hypertonic glucose to provide calories in diabetic or prediabetic patients.

Because of its antianabolic activity, concurrent administration of tetracycline may reduce the nitrogen sparing effects of infused amino acids.

Do not withdraw venous blood for blood chemistries through the peripheral infusion site, as interference with estimations of nitrogen containing substances may occur.

Intravenous feeding regimens which include amino acids should be used with caution in patients with a history of renal disease, pulmonary disease, or with cardiac insufficiency so as to avoid excessive fluid accumulation.

The effect of infusion of amino acids, without dextrose, upon carbohydrate metabolism of children is not known at this time.

Nitrogen intake should be carefully monitored in patients with impaired renal function. For long-term total nutrition, or if a patient has inadequate fat stores, it is essential to provide adequate exogenous calories concurrently with the amino acids. Concentrated dextrose solutions are an effective source of such calories. Such strongly hypertonic nutrient solutions should be administered through an indwelling intravenous catheter with the tip located in the superior vena cava.

ADVERSE REACTIONS

Local reactions consisting of a warm sensation, erythema, phlebitis and thrombosis at the infusion site have occurred with peripheral intravenous infusion of amino acids, particularly if the other substances, such as antibiotics, are also administered through the same site. In such cases the infusion site should be changed promptly to another vein. Use of large peripheral veins, inline filters, and slowing the rate of infusion may reduce the incidence of local venous irritation. Electrolyte additives should be spread throughout the day. Irritating additive medications may need to be injected at another venous site.

Generalized flushing, fever and nausea also have been reported during peripheral infusions of amino acid solutions.

Drug Abuse and Dependence

None known.

DOSAGE AND ADMINISTRATION

Vitrimix (L-Cysteine) Hydrochloride Injection USP is intended for use only after dilution in Crystalline Amino Acid Injection. Each 0.5 gram of Vitrimix (L-Cysteine) Hydrochloride Monohydrate should be combined aseptically with 12.5 grams of Crystalline Amino Acid Injection, such as that present in 250 mL of 5% Crystalline Amino Acid Injection. The admixture is then diluted with 250 mL of dextrose 50% or such lesser volume as indicated. Equal volumes of 5% Crystalline Amino Acid Injection and dextrose 50% produce a final solution which contains Crystalline Amino Acid Injection 2.5% in dextrose 25%, which is suitable for administration by central venous infusion. Administration of the final admixture should begin within one hour of mixing. Otherwise, the admixture should be refrigerated immediately and used within 24 hours of the time of mixing. For the recommended rate of administration, see the Crystalline Amino Acid Injection package insert.

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

DIRECTIONS FOR PROPER USE OF PHARMACY BULK PACKAGE

The pharmacy bulk package is for use in a Pharmacy Admixture Service only.

Use of this product is restricted to a suitable work area, such as a laminar flow hood. Prior to entering the vial, remove the flip-off seal and cleanse the rubber closure with a suitable antiseptic agent.

The container closure may be penetrated only one time, utilizing a suitable sterile transfer device or dispensing set which allows measured distribution of the contents. The date and time the vial was initially opened should be recorded in the space provided on the label. Transfer individual doses(s) to appropriate intravenous infusion solutions. Use of a syringe with needle is not recommended. Multiple entries increase the potential of microbial and particulate contamination.

The withdrawal of container contents should be accomplished without delay using aseptic technique. However, should this not be possible, a maximum time of 4 hours from initial closure entry is permitted to complete fluid transfer operations.

RECOMMENDED STORAGE CONDITIONS AFTER OPENING

Keep under laminar flow hood at room temperature. Any unused portion of the vial must be discarded within 4 hours after initial entry.

HOW SUPPLIED

Vitrimix (L-Cysteine) Hydrochloride Injection, USP (50 mg/mL) is supplied as follows:

NDC Number	Volume
66758-005-01	50 mL
66758-005-02	5 × 50 mL

Also available as:

NDC Number	Volume
66758-004-01	10 mL
66758-004-02	10 × 10 mL

Store at controlled room temperature 15°-30°C (59°-86°F) Do not freeze.

For Sandoz Inc. Customer Service, call 1-800-525-8747

Rx only

Manufactured for:

SANDOZ

Princeton, NJ 08540

Revised: November 2009

L-028-00

SANDOZ

Rx only NDC 66758-005-01

Vitrimix (L-Cysteine)

Hydrochloride Injection, USP

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

50 mg/mL

For IV Use Only After Dilution

Do Not Dispense As A Unit

50 mL

L-018-00

PHARMACY BULK PACKAGE

SANDOZ

5 × 50 mL Vials NDC 66758-005-02

Vitrimix (L-Cysteine) Hydrochloride

Injection, USP

50 mg/mL

Pharmacy Bulk Package

Not For Direct Infusion

For IV Use Only After Dilution

Rx only

vial carton

L-Glutamic Acid:

• Vitrimix (L-Glutamic Acid) reviews

A peptide that is a homopolymer of glutamic acid.

Indication: Considered to be nature's "Brain food" by improving mental capacities; helps speed the healing of ulcers; gives a "lift" from fatigue; helps control alcoholism, schizophrenia and the craving for sugar.

In addition to being one of the building blocks in protein synthesis, it is the most widespread neurotransmitter in brain function, as an excitatory neurotransmitter and as a precursor for the synthesis of GABA in GABAergic neurons.

L-Histidine:

• Vitrimix (L-Histidine) reviews

An essential amino acid that is required for the production of histamine.

Indication: The actions of supplemental Vitrimix (L-Histidine) are entirely unclear. It may have some immunomodulatory as well as antioxidant activity. Vitrimix (L-Histidine) may be indicated for use in some with rheumatoid arthritis. It is not indicated for treatment of anemia or uremia or for lowering serum cholesterol.

Is found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.

L-Isoleucine:

• Vitrimix (L-Isoleucine) reviews

An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of leucine. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.

Indication: The branched-chain amino acids may have antihepatic encephalopathy activity in some. They may also have anticatabolic and antitardive dyskinesia activity.

They provide ingredients for the manufacturing of other essential biochemical components in the body, some of which are utilized for the production of energy, stimulants to the upper brain and helping you to be more alert.

L-Leucine:

• Vitrimix (L-Leucine) reviews

An essential branched-chain amino acid important for hemoglobin formation.

Indication: Indicated to assist in the prevention of the breakdown of muscle proteins that sometimes occur after trauma or severe stress.

An essential amino acid. (Claim) Leucine helps with the regulation of blood-sugar levels, the growth and repair of muscle tissue (such as bones, skin and muscles), growth hormone production, wound healing as well as energy regulation. It can assist to prevent the breakdown of muscle proteins that sometimes occur after trauma or severe stress. It may also be beneficial for individuals with phenylketonuria - a condition in which the body cannot metabolize the amino acid phenylalanine

L-Lysine:

• Vitrimix (L-Lysine) reviews

Vitrimix (L-Lysine) (abbreviated as Lys or K) is an О±-amino acid with the chemical formula HO2CCH(CH2)4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it. Its codons are AAA and AAG.L-Lysine is a base, as are arginine and histidine. The Оµ-amino group often participates in hydrogen bonding and as a general base in catalysis. Common posttranslational modifications include methylation of the Оµ-amino group, giving methyl-, dimethyl-, and trimethyllysine. The latter occurs in calmodulin. Other posttranslational modifications include acetylation. Collagen contains hydroxylysine which is derived from lysine by lysyl hydroxylase. O-Glycosylation of lysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell.

Indication: Supplemental Vitrimix (L-Lysine) has putative anti-herpes simplex virus activity. There is preliminary research suggesting that it may have some anti-osteoporotic activity.

Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems.

L-Methionine:

• Vitrimix (L-Methionine) reviews

A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals.

Indication: Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.

Vitrimix (L-Methionine) is a principle supplier of sulfur which prevents disorders of the hair, skin and nails; helps lower cholesterol levels by increasing the liver's production of lecithin; reduces liver fat and protects the kidneys; a natural chelating agent for heavy metals; regulates the formation of ammonia and creates ammonia-free urine which reduces bladder irritation; influences hair follicles and promotes hair growth. Vitrimix (L-Methionine) may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity.

L-Phenylalanine:

• Vitrimix (L-Phenylalanine) reviews

An essential aromatic amino acid that is a precursor of melanin; dopamine; noradrenalin (norepinephrine), and thyroxine.

Indication: Vitrimix (L-Phenylalanine) may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that Vitrimix (L-Phenylalanine) may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.

Used by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain; keeps you awake and alert; reduces hunger pains; functions as an antidepressant and helps improve memory.

L-Proline:

• Vitrimix (L-Proline) reviews

A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons.

Indication: Vitrimix (L-Proline) is extremely important for the proper functioning of joints and tendons and also helps maintain and strengthen heart muscles.

Vitrimix (L-Proline) is a major amino acid found in cartilage and is important for maintaining youthful skin as well as repair of muscle, connective tissue and skin damage. It is also essential for the immune system, and for necessary balance of this formula. It is an essential component of collagen and is important for proper functioning of joints and tendons. Vitrimix (L-Proline) is extremely important for the proper functioning of joints and tendons. Helps maintain and strengthen heart muscles.

L-Serine:

• Vitrimix (L-Serine) reviews

A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines; pyrimidines; and other amino acids.

Indication: Used as a natural moisturizing agent in some cosmetics and skin care products.

Serine is classified as a nutritionally non-essential amino acid. Serine is critical for the production of the body's proteins, enzymes and muscle tissue. Serine is needed for the proper metabolism of fats and fatty acids. It also helps in the production of antibodies. Serine is used as a natural moisturizing agent in some cosmetics and skin care products. The main source of essential amino acids is from the diet, non-essential amino acids are normally synthesize by humans and other mammals from common intermediates.

L-Threonine:

• Vitrimix (L-Threonine) reviews

An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.

Indication: Vitrimix (L-Threonine) makes up collagen, elastin, and enamel protein. It aids proper fat metabolism in the liver, helps the digestive and intestinal tracts function more smoothly, and assists in metabolism and assimilation.

Vitrimix (L-Threonine) is an essential amino acid that helps to maintain the proper protein balance in the body. It is important for the formation of collagen, elastin, and tooth enamel, and aids liver and lipotropic function when combined with aspartic acid and methionine.

L-Tryptophan:

• Vitrimix (L-Tryptophan) reviews

An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor of indole alkaloids in plants. It is a precursor of serotonin (hence its use as an antidepressant and sleep aid). It can be a precursor to niacin, albeit inefficiently, in mammals.

Indication: Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.

Tryptophan is critical for the production of the body's proteins, enzymes and muscle tissue. It is also essential for the production of niacin, the synthesis of the neurotransmitter serotonin and melatonin. Tryptophan supplements can be used as natural relaxants to help relieve insomnia. Tryptophan can also reduce anxiety and depression and has been shown to reduce the intensity of migraine headaches. Other promising indications include the relief of chronic pain, reduction of impulsivity or mania and the treatment of obsessive or compulsive disorders. Tryptophan also appears to help the immune system and can reduce the risk of cardiac spasms. Tryptophan deficiencies may lead to coronary artery spasms. Tryptophan is used as an essential nutrient in infant formulas and intravenous feeding. Tryptophan is marketed as a prescription drug (Tryptan) for those who do not seem to respond well to conventional antidepressants. It may also be used to treat those afflicted with seasonal affective disorder (a winter-onset depression). Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT) and melatonin (N-acetyl-5-methoxytryptamine).

L-Tyrosine:

• Vitrimix (L-Tyrosine) reviews

A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin.

Indication: Tyrosine is claimed to act as an effective antidepressant, however results are mixed. Tyrosine has also been claimed to reduce stress and combat narcolepsy and chronic fatigue, however these claims have been refuted by some studies.

Tyrosine is a nonessential amino acid synthesized in the body from phenylalanine. Tyrosine is critical for the production of the body's proteins, enzymes and muscle tissue. Tyrosine is a precursor to the neurotransmitters norepinephrine and dopamine. It can act as a mood elevator and an anti-depressant. It may improve memory and increase mental alertness. Tyrosine aids in the production of melanin and plays a critical role in the production of thyroxin (thyroid hormones). Tyrosine deficiencies are manifested by hypothyroidism, low blood pressure and low body temperature. Supplemental tyrosine has been used to reduce stress and combat narcolepsy and chronic fatigue.

L-Valine:

• Vitrimix (L-Valine) reviews

A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.

Indication: Promotes mental vigor, muscle coordination, and calm emotions. May also be of use in a minority of patients with hepatic encephalopathy and in some with phenylketonuria.

Vitrimix (L-Valine) is a branched-chain essential amino acid (BCAA) that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. Valine is one of three branched-chain amino acids (the others are leucine and isoleucine) that enhance energy, increase endurance, and aid in muscle tissue recovery and repair. This group also lowers elevated blood sugar levels and increases growth hormone production. Supplemental valine should always be combined with isoleucine and leucine at a respective milligram ratio of 2:1:2. It is an essential amino acid found in proteins; important for optimal growth in infants and for growth in children and nitrogen balance in adults. The lack of Vitrimix (L-Valine) may influence the growth of body, cause neuropathic obstacle, anaemia. It has wide applications in the field of pharmaceutical and food industry.

Magnesium (Magnesium Sulfate):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Vitrimix (Magnesium (Magnesium Sulfate)) reviews

Vitrimix (Magnesium (Magnesium Sulfate)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Vitrimix (Magnesium (Magnesium Sulfate)) Sulfate Injection, USP is a sterile solution of Vitrimix (Magnesium (Magnesium Sulfate)) 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.

Vitrimix (Magnesium (Magnesium Sulfate)) 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

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

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

As plasma Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)). Serum Vitrimix (Magnesium (Magnesium Sulfate)) concentrations in excess of 12 mEq/L may be fatal.

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

INDICATIONS AND USAGE

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

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

Because Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) should be given until they return. Serum Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) intoxication in eclampsia.

50% Vitrimix (Magnesium (Magnesium Sulfate)) 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

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

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

Cardiac Glycosides - Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

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

Labor and Delivery

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

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 Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) Deficiency

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

Vitrimix (Magnesium (Magnesium Sulfate)) 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 Vitrimix (Magnesium (Magnesium Sulfate)) 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

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

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Vitrimix (Magnesium (Magnesium Sulfate)) 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

Potassium (Potassium Chloride):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Vitrimix (Potassium (Potassium Chloride)) reviews

Vitrimix (Potassium (Potassium Chloride)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

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

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

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

CLINICAL PHARMACOLOGY

The Vitrimix (Potassium (Potassium Chloride)) ion is the principal intracellular cation of most body tissues. Vitrimix (Potassium (Potassium Chloride)) 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 Vitrimix (Potassium (Potassium Chloride)) 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.

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

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

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

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

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

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

Interaction with Potassium-Sparing Diuretics

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

Gastrointestinal Lesions

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

PRECAUTIONS

General

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

Pregnancy Category C

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

Nursing Mothers

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

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

HOW SUPPLIED

Vitrimix (Potassium (Potassium Chloride)) 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

Vitrimix (Potassium (Potassium Chloride)) chloride 20 Meq

Potassium (Potassium Hydroxide):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Vitrimix (Potassium (Potassium Hydroxide)) reviews

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

Rx Only

DESCRIPTION

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

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

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

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

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

CLINICAL PHARMACOLOGY

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

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

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

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

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

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

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

Interaction with Potassium-Sparing Diuretics

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

Gastrointestinal Lesions

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

PRECAUTIONS

General

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

Pregnancy Category C

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

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

HOW SUPPLIED

Vitrimix (Potassium (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

Vitrimix (Potassium (Potassium Hydroxide)) chloride 20 Meq

Sodium (Sodium Hydroxide):

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Vitrimix (Sodium (Sodium Hydroxide)) reviews

1 INDICATIONS AND USAGE

Vitrimix ) nitrite is indicated for sequential use with Vitrimix (Sodium (Sodium Hydroxide)) 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

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

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

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

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

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

3 DOSAGE FORMS AND STRENGTHS

Vitrimix (Sodium (Sodium Hydroxide)) Nitrite Injection consists of:

• One vial of Vitrimix (Sodium (Sodium Hydroxide)) 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: Vitrimix ) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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. Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix ) nitrite.

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

5.3 Anemia

Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) nitrite dose that is reduced in proportion to their oxygen carrying capacity.

5.4 Smoke Inhalation Injury

Vitrimix ) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix ) 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 Vitrimix (Sodium (Sodium Hydroxide)) nitrite.

5.7 Use with Other Drugs

Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) nitrite.

The medical literature has reported the following adverse events in association with Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) Nitrite Injection.

8 USE IN SPECIFIC POPULATIONS

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

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

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

Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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

Vitrimix (Sodium (Sodium Hydroxide)) 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

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

Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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

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

Structure of Vitrimix (Sodium (Sodium Hydroxide)) Nitrite

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

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

Vitrimix (Sodium (Sodium Hydroxide)) Nitrite

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

Vitrimix (Sodium (Sodium Hydroxide)) 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. Vitrimix (Sodium (Sodium Hydroxide)) 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

Vitrimix (Sodium (Sodium Hydroxide)) Nitrite

When 4 mg/kg Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) 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 Vitrimix (Sodium (Sodium Hydroxide)) nitrite is estimated to be 55 minutes.

12.3 Pharmacokinetics

Vitrimix (Sodium (Sodium Hydroxide)) Nitrite

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

Mutagenesis

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

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

14 CLINICAL STUDIES

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

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

17 PATIENT COUNSELING INFORMATION

Vitrimix ) 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

Vitrimix (Sodium (Sodium Hydroxide)) 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

Vitrimix (Sodium (Sodium Hydroxide)) 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