Vitamin K Drug Information

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

• Multiple vitamins injection (adult) 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 )
• Multiple vitamins injection (adult) is for administration by intravenous infusion after dilution ( 2.1 )
• Recommended daily dosage is 10 mL ( 2.1 )
• Multiple vitamins injection (adult) is supplied as a pharmacy bulk package. Pharmacy Bulk Package : Add the contents of Vial 1 to the contents of Vial 2. This provides ten 10 mL daily doses. Take 10 mL from Vial 2 and add to not less than 500 mL, and preferably 1,000 mL, of intravenous dextrose, saline or similar infusion solutions. ( 2.2 )
• After dilution in an intravenous infusion, refrigerate resulting solution unless used immediately. Use solution within 24 hours after dilution ( 2.2 )
• Monitor blood vitamin concentrations ( 2.3 )
• See Full Prescribing Information for drug incompatibilities ( 2.4 ) 2.1 Important Dosage Instructions Multiple vitamins injection (adult) 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 . Multiple vitamins injection (adult) is supplied as a pharmacy bulk package for intravenous use intended for administration by intravenous infusion after dilution. Multiple vitamins injection (adult) Pharmacy Bulk Package:
• Provides ten 10 mL daily doses when the content of vial 1 is transferred into the content of vial 2. One 10 mL dose is then added directly to intravenous fluid. Pharmacy bulk package of multiple vitamins injection (adult) 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 )]. Patients with multiple vitamin deficiencies or with increased vitamin requirements may need multiple daily dosages as indicated. Some patients do not maintain adequate levels of certain vitamins when this formulation in recommended amounts is the only source of vitamins. 2.2 Preparation and Administration Instructions Do not administer multiple vitamins injection (adult) as a direct, undiluted intravenous injection as it may cause dizziness, faintness, and possible tissue irritation . Multiple vitamins injection (adult) 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 1 into the contents of Vial 2 to provide ten 10 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.
• One daily 10 mL dose should be added directly to at least 500 mL to 1,000 mL, of intravenous dextrose, saline or similar infusion solutions.
• After multiple vitamins injection (adult) 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 multiple vitamins injection (adult), particularly A, D and riboflavin, are light sensitive. 2.3 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. 2.4 Drug Incompatibilities
• Multiple vitamins injection (adult) 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 multiple vitamins injection (adult) may react with bisulfite solutions such as sodium bisulfite or vitamin K bisulfate.
• Do not add multiple vitamins injection (adult) 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 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 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.

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

• 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 )

Signs and symptoms of acute or chronic overdosage may be those of individual multiple vitamins injection (adult) component toxicity. In postmarketed surveillance, overdosage with multiple vitamins injection (adult) at two times the prescribed dose did not result in toxicity.