Infuvite Pediatric

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 K₁, folic acid, biotin, and vitamin B₁₂ .

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 [see Dosage and Administration (2.2 and 2.3)].
• 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 [see Dosage and Administration (2.2 and 2.3)].

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 [see Warnings and Precautions (5.8)].

INFUVITE PEDIATRIC Single Dose (see Table 1):

One daily dose of Vial 1 (1.2 mL, 2.6 mL or 4 mL) and one daily dose of Vial 2 (0.3 mL, 0.65 mL or 1 mL) based on the patient’s weight are added directly to a specified volume of an intravenous fluid [see Dosage and Administration (2.3)] (see Table 1).

INFUVITE PEDIATRIC Pharmacy Bulk Package (see Table 2):

The recommended daily dosage volume of combined content of vials 1 and 2 (1.5 mL, 3.25 mL or 5 mL) is based on the patient’s weight and then added directly to the specific volume of an intravenous fluid [see Dosage and Administration (2.3)].

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.

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.

• 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.

INFUVITE PEDIATRIC contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration in pediatric patients with renal impairment. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solution, 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. To prevent aluminum toxicity periodically monitor aluminum levels with prolonged parenteral administration of INFUVITE PEDIATRIC.

Allergic reactions such as urticaria, shortness of breath, wheezing and angioedema have been reported following intravenous administration of thiamine, which is found in INFUVITE PEDIATRIC. There have been rare reports of anaphylaxis following intravenous doses of thiamine. No fatal anaphylaxis associated with INFUVITE PEDIATRIC has been reported.

Hypervitaminosis A, manifested by nausea, vomiting, headache, dizziness, blurred vision has been reported in patients with renal failure receiving 1.5 mg/day retinol and in patients with liver disease. Therefore, supplementation of renal failure patients and patients with liver disease with vitamin A, an ingredient found in INFUVITE PEDIATRIC, should be undertaken with caution [see Use in Specific Populations (8.6 and 8.7)]. Blood levels of Vitamin A should be monitored periodically.

INFUVITE PEDIATRIC contains Vitamin K which may decrease the anticoagulant action of warfarin. In patients who are on warfarin anticoagulant therapy receiving INFUVITE PEDIATRIC monitor blood levels of prothrombin/INR to determine if dose of warfarin needs to be adjusted.

INFUVITE PEDIATRIC contains folic acid and cyanocobalamin which can mask serum deficiencies of folic acid and cyanocobalamin in patients with megaloblastic anemia. Avoid the use of INFUVITE PEDIATRICS in patients with suspected or diagnosed megaloblastic anemia prior to blood sampling for the detection of the folic acid and cyanocobalamin deficiencies.

In patients receiving parenteral multivitamins such as with INFUVITE PEDIATRIC, blood vitamin concentrations should be periodically monitored to determine if vitamin deficiencies or excesses are developing. INFUVITE PEDIATRIC may not correct long-standing specific vitamin deficiencies. The administration of additional doses of specific vitamins may be required [see Dosage and Administration ( 2.2)].

INFUVITE PEDIATRIC contains vitamin C which is also known as ascorbic acid. Ascorbic acid in the urine may cause false negative urine glucose results.

Additional vitamin E supplementations of patients receiving INFUVITE PEDIATRIC may result in elevated blood concentrations of vitamin E and potential vitamin E toxicity in infants. Avoid additional oral or parental doses of vitamin E in infants. Daily dose of INFUVITE PEDIATRIC contains adequate concentrations of vitamin E required to achieve normal blood levels of vitamin E.

Lower vitamin A concentrations may occur after administration of INFUVITE PEDIATRIC due to the adherence of Vitamin A to plastic. Monitor blood vitamin A concentrations periodically. Additional administration of therapeutic doses of vitamin A may be required, especially in low-birth weight infants.

E-Ferol syndrome manifested by thrombocytopenia, renal dysfunction, hepatomegaly, cholestasis, ascites, hypotension and metabolic acidosis 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.

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 [see Warnings and Precautions (5.4)].

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.

Hydralazine, Isoniazid: Concomitant administration of hydralazine or isoniazid may increase pyridoxine requirements.

Phenytoin: Phenytoin may decrease serum folic acid concentrations.

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.

Risk Summary

Multiple vitamins present in INFUVITE PEDIATRIC are also present in human milk. Administration of the approved recommended dose of Infuvite Pediatric in parental nutrition is not expected to cause harm to a breastfed infant. There is no information on the effects of Infuvite Pediatric on milk production. Lactating patients should follow the U.S. Recommended Daily Allowances for their condition, because their vitamin requirements may exceed those of nonlactating patients. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for INFUVITE PEDIATRIC and any potential adverse effects on the breastfed child from INFUVITE PEDIATRIC or from the underlying maternal condition.

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 [see Warnings and Precautions ( 5.1 )].

Additional vitamin E supplementations of infants receiving INFUVITE PEDIATRIC may result in elevated blood concentrations of vitamin E and potential vitamin E toxicity [see Warnings and Precautions ( 5.8 )].

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 [see Warnings and Precautions (5.10)].

INFUVITE PEDIATRIC has not been studied in patients with renal impairment. Monitor renal function, calcium, phosphorus and vitamin A levels in patients with renal impairment [see Warnings and Precautions (5.1 and 5.3)].

INFUVITE PEDIATRIC has not been studied in patients with liver impairment. Monitor vitamin A levels in patients with liver disease [see Warnings and Precautions ( 5.3 )].

Carcinogenicity, mutagenicity, and fertility studies have not been performed with INFUVITE PEDIATRIC.