Ascorbic Acid, Vitamin A Palmitate, Cholecalciferol, Thiamine Hydrochloride, Riboflavin 5-Phosphate Sodium, Pyridoxine Hydrochloride, Niacinamide, Dexpanthenol, Alpha-Tocopherol Acetate, Vitamin K1, Folic Acid, Biotin, Cyanocobalamin

Multiple vitamins injection (adult) is a combination of vitamins indicated for the prevention of vitamin deficiency in adults and children aged 11 and older receiving parenteral nutrition. The physician should not await the development of clinical signs of vitamin deficiency before initiating vitamin therapy. Multiple vitamins injection (adult) is a combination of vitamins indicated for prevention of vitamin deficiency in adults and children aged 11 and older receiving parenteral nutrition ( 1 )

Multiple vitamins injection (adult) Single Dose: is an injection for intravenous administration consisting of two vials labeled Vial 1 (5 mL) and Vial 2 (5 mL). For the vitamin strengths [ s ee Description ( 11 ) ]. Vial 1 (Single Dose) is supplied as clear, yellow to orange colored solution in amber glass vial closed with a rubber stopper, aluminum flip-off seals of white color button. Vial 2 (Single Dose) is supplied as clear, off-white to pale yellow colored solution in amber glass vial closed with a rubber stopper, aluminum flip-off seals of dark blue color button.

• Multiple vitamins injection (adult) supplied as single dose is an injection consisting of two vials labeled Vial 1 (5 mL) and Vial 2 (5 mL) ( 3 )

Multiple vitamins injection (adult) is contraindicated in patients who have

• An existing hypervitaminosis, or
• A history of hypersensitivity due to any vitamins or excipients contained in this formulation. Hypersensitivity to any of the vitamins or excipients ( 4 ) Existing hypervitaminosis ( 4 )

Risk of Aluminum Toxicity: For at risk patients (renal failure or those with prolonged therapy), consider periodic monitoring of aluminum levels ( 5.1 ) Allergic Reactions: To thiamine may occur ( 5.2 ) Hypervitaminosis A : Patients with renal failure or liver disease may be at higher risk ( 5.3 ) Decreased Anticoagulant Effect of Warfarin : Monitor INR ( 5.4 , 7.1 ) Interferes with Megaloblastic Anemia Diagnosis: Avoid during testing for this disorder ( 5.5 ) Risk of Vitamin Deficiencies or Excesses: Monitor blood vitamin concentrations ( 5.6 ) False Negative Urine Glucose Tests: Due to vitamin C ( 5.7 )

5.1 Aluminum Toxicity Multiple vitamins injection (adult) 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 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 multiple vitamins injection (adult) in patients with renal impairment.

5.2 Allergic Reactions to Thiamine Allergic reactions such as urticaria, shortness of breath, wheezing and angioedema have been reported following intravenous administration of thiamine, which is found in multiple vitamins injection (adult). There have been rare reports of anaphylactoid reactions following intravenous doses of thiamine. No fatal anaphylactoid reactions associated with multiple vitamins injection (adult) have been reported. 5.3. Hypervitaminosis A 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 multiple vitamins injection (adult), should be undertaken with caution [see Use in Specific Populations ( 8.6 and 8.7)].

5.4 Decreased Anticoagulant Effect of Warfarin Multiple vitamins injection (adult) contains Vitamin K, which may decrease the anticoagulant action of warfarin. In patients who are on warfarin anticoagulant therapy receiving multiple vitamins injection (adult) monitor blood levels of prothrombin/INR to determine if dose of warfarin needs to be adjusted.

5.5 Interference with Diagnosis of Megaloblastic Anemia Multiple vitamins injection (adult) contains folic acid and cyanocobalamin which can mask serum deficiencies of folic acid and cyanocobalamin in patients with megaloblastic anemia. Avoid the use of multiple vitamins injection (adult) in patients with suspected or diagnosed megaloblastic anemia prior to blood sampling for the detection of the folic acid and cyanocobalamin deficiencies.

5.6 Potential to Develop Vitamin Deficiencies or Excesses In patients receiving parenteral multivitamins such as with multiple vitamins injection (adult), blood concentration should be periodically monitored to determine if deficiencies or excesses are developing. Multiple vitamins injection (adult) may not correct long-standing specific vitamin deficiencies. The administration of additional therapeutic doses of specific vitamins may be required [see Dosage and Administration ( 2.3 )].

5.7 Interference with Urine Glucose Testing Multiple vitamins injection (adult) contains vitamin C which is also known as ascorbic acid. Ascorbic acid in the urine may cause false negative urine glucose results.

The following adverse reactions are discussed in greater detail in other section 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 multiple vitamins injection (adult). 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 and anaphylactoid reactions including shortness of breath, wheezing and angioedema, rash, erythema, pruritis, headache, dizziness, agitation, anxiety, diplopia ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

A number of interactions between vitamins and drugs have been reported. The following are examples of these types of interactions: Effect of multiple vitamins injection (adult) 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 multiple vitamins injection (adult):
• Hydralazine, Isoniazid: Concomitant administration of hydralazine or isoniazid may increase pyridoxine requirements ( 7.2 ).
• Phenytoin: May decrease folic acid concentrations ( 7.2 )
• Chloramphenicol: In patients with pernicious anemia, the hematologic response to vitamin B 12 therapy may be inhibited ( 7.2 )

7.1 Drug Interactions Affecting Co-Administered Drugs Warfarin: Vitamin K, a component of multiple vitamins injection (adult), antagonizes the anticoagulant action of warfarin. In patients who are co-administered warfarin and multiple vitamins injection (adult), 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. Chloramphenicol: In patients with pernicious anemia, the hematologic response to vitamin B 12 therapy may be inhibited by chloramphenicol.

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 in patients with renal impairment ( 8.6 ) Hepatic Impairment: Monitor vitamin A level in patients with liver disease, high alcohol consumption ( 8.7 )

8.1 Pregnancy Risk Summary Administration of the approved recommended dose of multiple vitamins injection (adult) 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 multiple vitamins injection (adult). 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 to 4% and 15 to 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 woman’s nutritional requirements cannot be fulfilled by oral or enteral intake.

8.2 Lactation Risk Summary Multiple vitamins present in multiple vitamins injection (adult) are also present in human milk. Administration of the approved recommended dose of multiple vitamins injection (adult) In parental nutrition is not expected to cause harm to a breastfed infant. There is no information on the effects of multiple vitamins injection (adult) 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 multiple vitamins injection (adult) and any potential adverse effects on the breastfed child from multiple vitamins injection (adult) or from the underlying maternal condition.

8.4 Pediatric Use Safety and effectiveness in children below the age of 11 years have not been established.

8.5 Geriatric Use Safety and effectiveness for geriatric use have not been established.

8.6 Renal Impairment Multiple vitamins injection (adult) 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 Multiple vitamins injection (adult) has not been studied in patients with liver impairments. Monitor vitamin A level in patients with liver disease, high alcohol consumption [ see Warnings and Precautions ( 5.3 ) ].