Infuvite Pediatric Drug Information

INFUVITE PEDIATRIC is a combination of vitamins indicated for the prevention of vitamin deficiency in pediatric patients up to 11 years of age receiving parenteral nutrition. The physician should not await the development of clinical signs of vitamin deficiency before initiating vitamin therapy.

Important Dosage and Administration Instructions INFUVITE PEDIATRIC is a combination product that contains the following vitamins: ascorbic acid, vitamin A, vitamin D, thiamine, riboflavin, pyridoxine, niacinamide, dexpanthenol, vitamin E, vitamin K 1, folic acid, biotin, and vitamin B 12. INFUVITE PEDIATRIC is supplied as a single dose or as a pharmacy bulk package for intravenous use intended for administration by intravenous infusion after dilution: • INFUVITE PEDIATRIC Single Dose consists of two vials. A weight-based volume from each vial must be added directly to dextrose or saline solution prior to intravenous administration. • INFUVITE PEDIATRIC Pharmacy Bulk Package consists of two pharmacy bulk vials which must be mixed prior to use.

The mixed solution will provide multiple daily doses which must be diluted prior to intravenous administration. Pharmacy bulk package of INFUVITE PEDIATRIC is intended for dispensing of single doses to multiple patients in a pharmacy admixture program and is restricted to the preparation of admixtures for infusion.

Dosage Information

• The recommended daily dosage volume is based on the patient's actual weight: less than 1 kg, 1 kg to less than 3 kg, and 3 kg or greater. Patients with multiple vitamin deficiencies or with increased vitamin requirements may need multiple daily dosages as indicated or additional doses of individual vitamins. Supplemental vitamin A may be required for low-birth weight infants. Additional daily dosages of Vitamin E in infants are not recommended.
• Table 1: Recommended Weight-Based Dosage of INFUVITE PEDIATRIC Single-Dose INFUVITE PEDIATRIC Pharmacy Bulk Package (see Table 2 ): The recommended daily dosage volume of combined content of vials mL or 5 mL is based on the patient’s weight and then added directly to the specific volume of an intravenous fluid.

Preparation and Administration Instructions

Do not administer INFUVITE PEDIATRIC as a direct, undiluted intravenous injection as it may cause dizziness, faintness, and possible tissue irritation. INFUVITE PEDIATRIC Single Dose: • Use only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). • Add one weight-based dose of Vial 1 (1.2 mL, 2.6 mL or 4 mL) and one weight-based dose of Vial 2 (0.3 mL, 0.65 mL or 1 mL) directly to at least 100 mL of intravenous dextrose or saline solution. • Discard unused portion. • Visually inspect for particulate matter and discoloration prior to administration. • After INFUVITE PEDIATRIC is diluted in an intravenous infusion, refrigerate the resulting solution unless it is to be used immediately, and use the solution within 24 hours after dilution. • Minimize exposure to light because some of the vitamins in INFUVITE PEDIATRIC, particularly A, D and riboflavin, are light sensitive. INFUVITE PEDIATRIC Pharmacy Bulk Package: • Use only in a suitable work area such as a laminar flow hood (or an equivalent clean air compounding area). • Transfer the contents of Vial 2 (10 mL of solution) into the contents of Vial 1 (40 mL of solution).

The mixed solution (50 mL) will provide thirty-three 1.5 mL single doses, fifteen 3.25 mL single doses or ten 5 mL single doses. • Each bulk vial closure shall be penetrated only one time with a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. • Once the closure system has been penetrated, complete dispensing from the pharmacy bulk vial should be completed within 4 hours. The mixed solution may be refrigerated and stored for up to 4 hours. • Discard unused portion. • Visually inspect for particulate matter and discoloration prior to administration. • Add one dose directly to at least 100 mL of intravenous dextrose or saline solution for each patient. • After INFUVITE PEDIATRIC is diluted in an intravenous infusion, refrigerate the resulting solution unless it is to be used immediately, and use the solution within 24 hours after dilution. • Minimize exposure to light because some of the vitamins in INFUVITE PEDIATRIC, particularly A, D and riboflavin, are light sensitive.

Monitoring Vitamin Blood Levels

Blood vitamin concentrations should be monitored to ensure maintenance of adequate levels, particularly in patients receiving parenteral multivitamins as the only source of vitamins for long periods of time.

Drug Incompatibilities • INFUVITE PEDIATRIC is not physically compatible with moderately alkaline solutions such as a sodium bicarbonate solution and other alkaline drugs such as acetazolamide sodium, aminophylline, ampicillin sodium, tetracycline HCl and chlorothiazide sodium. • Folic acid is unstable in the presence of calcium salts such as calcium gluconate. • Vitamin A and thiamine in INFUVITE PEDIATRIC may react with bisulfite solutions such as sodium bisulfite or vitamin K bisulfite. • Do not add INFUVITE PEDIATRIC directly to intravenous fat emulsions. • Consult appropriate references for additional listings of physical and chemical compatibility of solutions and drugs with the vitamin infusion when needed. If incompatibilities are identified, avoid admixture or Y-site administration with vitamin solutions.

• The following adverse reactions are discussed in greater detail in other sections of the labeling.
• Allergic reactions to thiamine.
• Hypervitaminosis A The following adverse reactions have been identified during postapproval use of INFUVITE PEDIATRIC. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Dermatologic: rash, erythema, pruritis CNS: headache, dizziness, agitation, anxiety Ophthalmic: diplopia Adverse reactions have included anaphylaxis, rash, erythema, pruritis, headache, dizziness, agitation, anxiety, diplopia To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Drug Interactions Affecting Co-Administered Drugs Warfarin: Vitamin K, a component of INFUVITE PEDIATRIC, antagonizes the anticoagulant action of warfarin. In patients who are co-administered warfarin and INFUVITE PEDIATRIC, blood levels of prothrombin/INR should be monitored to determine if dose of warfarin needs to be adjusted.
• Antibiotics: Thiamine, riboflavin, pyridoxine, niacinamide, and ascorbic acid decrease antibiotic activities of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin.
• Bleomycin: Ascorbic acid and riboflavin inactivate bleomycin in vitro, thus the activity of bleomycin may be reduced.
• Levodopa: Pyridoxine may increase the metabolism of levodopa (decrease blood levels of levodopa) and decrease its efficacy.
• Phenytoin: Folic acid may increase phenytoin metabolism and lower the serum concentration of phenytoin resulting in increased seizure activity.
• Methotrexate: Folic acid may decrease a patient’s response to methotrexate therapy.

• Drug Interactions Affecting Vitamin Levels Hydralazine, Isoniazid: Concomitant administration of hydralazine or isoniazid may increase pyridoxine requirements.
• Phenytoin: Phenytoin may decrease serum folic acid concentrations.

Pregnancy Risk Summary Administration of the approved recommended dose of INFUVITE PEDIATRIC in parental nutrition is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pregnant patients should follow the U.S. Recommended Daily Allowances for pregnancy because their vitamin requirements may exceed those of nonpregnant patients.

Deficiency of essential vitamins may result in adverse pregnancy outcomes (see Clinical Considerations). Animal reproduction studies have not been conducted with INFUVITE PEDIATRIC. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo-Fetal Risk Deficiency of essential vitamins has been associated with adverse pregnancy and fetal outcomes, such as maternal folic acid deficiency and an increased risk of neural tube defects.

Therefore, parenteral nutrition with multiple vitamins injection should be considered if a pregnant patient’s nutritional requirements cannot be fulfilled by oral or enteral intake.

Pediatric Use INFUVITE PEDIATRIC is approved for the prevention of vitamin deficiency in pediatric patients up to 11 years old receiving parenteral nutrition. INFUVITE PEDIATRIC has not been studied in pediatric patients older than 11 years. INFUVITE PEDIATRIC contains aluminum that may be toxic for premature neonates.

Aluminum levels should be monitored periodically during administration of INFUVITE PEDIATRIC to premature neonates. Additional vitamin E supplementations of infants receiving INFUVITE PEDIATRIC may result in elevated blood concentrations of vitamin E and potential vitamin E toxicity. E-Ferol syndrome has been reported in low-birth weight infants following administration of polysorbates which are found in INFUVITE PEDIATRIC.

No E-Ferol syndrome associated with INFUVITE PEDIATRIC has been reported.

• INFUVITE PEDIATRIC is contraindicated in patients who have:
• An existing hypervitaminosis, or
• A history of hypersensitivity to any vitamins or excipients contained in this formulation.
• Hypersensitivity to any of vitamins or excipients
• Existing hypervitaminosis

Signs and symptoms of acute or chronic overdosage may be those of individual INFUVITE PEDIATRIC component toxicity. There is no clinical experience with INFUVITE PEDIATRIC overdosage.