PEDIATRIC INFUVITE MULTIPLE VITAMINS FOR INFUSION (Page 3 of 4)

5.8 Vitamin E Overdose in Infants Receiving Additional Vitamin E

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.

5.9 Risk of Low Vitamin A Levels

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.

5.10 Risk of E-Ferol Syndrome 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.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling.

•

Allergic reactions to thiamine [see Warnings and Precautions (5.2) ].

•

Hypervitaminosis A [see Warnings and Precautions (5.3) ]

The following adverse reactions have been identified during post-approval 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

7 DRUG INTERACTIONS

7.1 Drug Interactions Affecting Co-administered Drugs

A number of interactions between vitamins and drugs have been reported. The following are examples of these types of interactions:

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.

7.2 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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C.

INFUVITE PEDIATRIC has not been studied in pregnant women. Pregnant women should follow the U.S. recommended daily allowances for pregnancy because their vitamin requirements may exceed those of non-pregnant women. Animal reproduction studies have not been conducted with INFUVITE PEDIATRIC (multiple vitamins injection).

8.3 Nursing Mothers

INFUVITE PEDIATRIC has not been studied in nursing mothers. Lactating women may have vitamin requirements that exceed those of non-lactating women. Caution should be exercised when INFUVITE PEDIATRIC is administered to nursing mothers.

8.4 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 [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)].

8.6 Renal Impairment

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, 5.3) ].

8.7 Hepatic Impairment

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) ].

10 OVERDOSAGE

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.

11 DESCRIPTION

INFUVITE PEDIATRIC (multiple vitamins injection) is a sterile product consisting of two vials provided as a single dose or as a pharmacy bulk package for intravenous use intended for administration by intravenous infusion after dilution:

INFUVITE PEDIATRIC (multiple vitamins injection) supplied as single dose consists of:

(a) Vial 1 (4 mL); and

(b) Vial 2 (1 mL).

Vial 1 will provide one daily dose of 1.2 mL, 2.6 mL or 4 mL and Vial 2 will provide one daily dose of 0.3 mL, 0.65 mL or 1 mL [see Dosage and Administration (2.2)].

INFUVITE PEDIATRIC (multiple vitamins injection) supplied as pharmacy bulk package consists of:

(a) Vial 1 (40 mL Fill in 50 mL Vial); and

(b) Vial 2 (10 mL).

The mixed solution will provide many single doses [see Dosage and Administration (2.2)].

Each 4 mL of Vial 1 contains 10 vitamins and each 1 mL of Vial 2 contains 3 vitamins (see Table 3).

Table 3: INGREDIENTS IN INFUVITE PEDIATRIC FORMULATION

Vial 1
Active Ingredient	Quantity per 4 mL
Ascorbic acid (Vitamin C)	80 mg
Vitamin A* (as palmitate)	2,300 IU (equals 0.7 mg)
Vitamin D3 * (cholecalciferol)	400 IU (equals 10 mcg)
Thiamine (Vitamin B1 ) (as the hydrochloride)	1.2 mg
Riboflavin (Vitamin B2 ) (as riboflavin 5-phosphate sodium)	1.4 mg
Pyridoxine HCl (Vitamin B6 )	1 mg
Niacinamide	17 mg
Dexpanthenol (as d -pantothenyl alcohol)	5 mg
Vitamin E* (dl -α-tocopheryl acetate)	7 IU (equals 7 mg)
Vitamin K1 *	0.2 mg
* Polysorbate 80 is used to water solubilize the oil-soluble vitamins A, D, E, and K.
Inactive ingredients in 4 mL of Vial 1: 50 mg polysorbate 80, sodium hydroxide and/or hydrochloric acid for pH adjustment, and water for injection.
Vial 2
Active Ingredient	Quantity per 1 mL
Folic acid	140 mcg
Biotin	20 mcg
Vitamin B12 (cyanocobalamin)	1 mcg
Inactive ingredients in 1 mL of Vial 2: 75 mg mannitol, citric acid and/or sodium citrate for pH adjustment and water for injection.

INFUVITE PEDIATRIC (multiple vitamins injection) makes available a combination of oil-soluble and water-soluble vitamins in an aqueous solution, formulated for incorporation into intravenous solutions. The liposoluble vitamins A, D, E, and K have been solubilized in an aqueous medium with polysorbate 80, permitting intravenous administration of these vitamins.

INFUVITE PEDIATRIC contains no more than 30 mcg/L of aluminum (combined Vials 1 and 2).