Infuvite Pediatric

1 INDICATIONS AND USAGE 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. 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 ( 1 )

2 DOSAGE AND ADMINISTRATION • 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 (2.1) • INFUVITE PEDIATRIC is for administration by intravenous infusion after dilution ( 2.1 ) • Recommended daily dosage is based on patient’s actual weight ( 2.2 ): o INFUVITE PEDIATRIC Single Dose : ▪ Weight less than 1 kg : 1.2 mL of Vial 1 and 0.3 mL of Vial 2 ▪ Weight 1 kg to less than 3 kg : 2.6 mL of Vial 1 and 0.65 mL of Vial 2 ▪ Weight 3 kg or greater : 4 mL of Vial 1 and 1 mL of Vial 2 o INFUVITE PEDIATRIC Pharmacy Bulk Package : ▪ Weight less than 1 kg : 1.5 mL of combined content of Vials 1 and 2 ▪ Weight 1 kg to less than 3 kg : 3.25 mL of combined content of Vials 1 and 2 ▪ Weight 3 kg or greater : 5 mL of combined content of Vials 1 and 2. • Supplemental vitamin A may be required for low-birth weight infants ( 2.2 ) • INFUVITE PEDIATRIC is supplied as a single dose and as a pharmacy bulk package: o Single Dose consists of two vials labeled Vial 1 and Vial 2. Add one daily dose of Vial 1 and one daily dose of Vial 2 directly to at least 100 mL of intravenous dextrose or saline solution prior to intravenous use ( 2.3 ) o Pharmacy Bulk Package consists of two vials labeled Vial 1 and Vial 2. Transfer contents of Vial 2 to contents of Vial 1. Then, take 1.5 mL, 3.25 mL, or 5 mL from mixture and add to at least 100 mL of intravenous dextrose or saline solution prior to intravenous use ( 2.3 ) • After dilution in an intravenous infusion, refrigerate resulting solution unless used immediately. Use solution within 24 hours after dilution ( 2.3 ) • Monitor blood vitamin concentrations ( 2.4 ) • See Full Prescribing Information for drug incompatibilities ( 2.5 ). 2.1 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 [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 )] . 2.2 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 [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 ). Table 1: Recommended Weight-Based Dosage of INFUVITE PEDIATRIC Single-Dose Less than 1 kg 1 kg to less than 3 kg 3 kg or greater Daily Dosage …

3 DOSAGE FORMS AND STRENGTHS INFUVITE PEDIATRIC Single Dose is an injection consisting of two single-dose vials labeled Vial 1 (4 mL) and Vial 2 (1 mL). For the vitamin strengths [see Dosage and Administration ( 2.2 ) and Description ( 11 )] . INFUVITE PEDIATRIC Pharmacy Bulk Package is an injection consisting of two vials labeled Vial 1 (40 mL Fill in 50 mL Vial) and Vial 2 (10 mL). 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. For the vitamin strengths [see Dosage and Administration ( 2.2 ) and Description ( 11 )] . Vial 1 (Single Dose and Pharmacy Bulk Package) is supplied as clear, yellow to orange liquid in amber glass vial, closed with a rubber stopper, clear aluminum seal and a blue flip-off. Vial 2 (Single Dose and Pharmacy Bulk Package) is supplied as clear, colorless to pale yellow liquid in amber glass vial closed with a rubber stopper, clear aluminum seal and pink flip-off. • INFUVITE PEDIATRIC single dose is an injection consisting of two vials labeled Vial 1 (4 mL) and Vial 2 (1 mL) ( 3 ) • INFUVITE PEDIATRIC pharmacy bulk package is an injection consisting of two vials labeled Vial 1 (40 mL fill in 50 mL) and Vial 2 (10 mL) ( 3 ) • See Full Prescribing Information for vitamin strengths ( 11 )

4 CONTRAINDICATIONS 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 ( 4 ) • Existing hypervitaminosis ( 4 )

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 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 ( 6 ) 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.

7 DRUG INTERACTIONS A number of interactions between vitamins and drugs have been reported. The following are examples of these types of interactions. Effect of INFUVITE PEDIATRIC on other drugs: • Antibiotics : Thiamine, riboflavin, pyridoxine, niacinamide, and ascorbic acid decrease activities of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin ( 7.1 ) • Bleomycin : Ascorbic acid and riboflavin may reduce the activity of bleomycin ( 7.1 ) • Levodopa : Pyridoxine may decrease blood levels of levodopa and levodopa efficacy may decrease ( 7.1 ) • Phenytoin : Folic acid may decrease phenytoin blood levels and increase risk of seizure activity ( 7.1 ) • Methotrexate : Folic acid may decrease response to methotrexate ( 7.1 ) Effects of other drugs on INFUVITE PEDIATRIC: • Hydralazine, Isoniazid : Concomitant administration of hydralazine or isoniazid may increase pyridoxine requirements ( 7.2 ). • Phenytoin : May decrease folic acid concentrations ( 7.2 ) 7.1 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 [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 • Pregnancy and Lactation : Pregnant and lactating patients should follow the U.S. Recommended Daily Allowances for their condition, because their vitamin requirements may exceed those of nonpregnant and nonlactating patients ( 8.1 , 8.2) • Renal Impairment : Monitor renal function, calcium, phosphorus and vitamin A levels ( 8.6 ) • Hepatic Impairment : Monitor vitamin A levels ( 8.7 ) 8.1 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. 8.2 Lactation 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. 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 and 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 )].

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 D 3 * (cholecalciferol) 400 IU (equals 10 mcg) Thiamine (Vitamin B 1 ) (as the hydrochloride) 1.2 mg Riboflavin (Vitamin B 2 ) (as riboflavin 5-phosphate sodium) 1.4 mg Pyridoxine HCl (Vitamin B 6 ) 1 mg Niacinamide 17 mg Dexpanthenol (as d -pantothenyl alcohol) 5 mg Vitamin E * ( dl -α-tocopheryl acetate) 7 IU (equals 7 mg) Vitamin K 1 * 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 B 12 (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).

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.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied INFUVITE PEDIATRIC (multiple vitamins injection) is supplied as follows: Vial 1 (Single Dose and Pharmacy Bulk Package) is supplied as clear, yellow to orange liquid in amber glass vial, closed with a rubber stopper, clear aluminum seal and a blue flip-off. Vial 2 (Single Dose and Pharmacy Bulk Package) is supplied as clear, colorless to pale yellow liquid in amber glass vial closed with a rubber stopper, clear aluminum seal and pink flip-off. INFUVITE PEDIATRIC Single Dose: Carton contains total ten single-dose vials NDC 54643-5646-1 Five of Vial 1 (4 mL) NDC 54643-5648-1 Five of Vial 2 (1 mL) NDC 54643-5651-1 one Vial 1 plus one Vial 2 to be used for a single dose [see Dosage and Administration ( 2.2 and 2.3 )]. INFUVITE PEDIATRIC Pharmacy Bulk Package: Carton contains total two vials NDC 54643-5647-0 One Vial 1 (40 mL fill in 50 mL) NDC 54643-5653-0 One Vial 2 (10 mL) NDC 54643-5655-0 Mixed contents of Vial 2 with Vial 1 provide thirty-three 1.5 mL single doses, fifteen 3.25 mL single doses or 10 single 5 mL doses [see Dosage and Administration ( 2.2 and 2.3 )]. Storage and Handling Minimize exposure of INFUVITE PEDIATRIC to light because vitamins A, D and riboflavin are light sensitive. Store under refrigeration 2°C to 8°C (36°F to 46°F).