2.1 Important Dosage and Administration Instructions

M.V.I.-12 is a combination product that contains the following vitamins: ascorbic acid, vitamin A, vitamin D, thiamine, riboflavin, pyridoxine, niacinamide, dexpanthenol, vitamin E, folic acid, biotin, and vitamin B12.

M.V.I.-12 is supplied as a pharmacy bulk package for intravenous use intended for administration by intravenous infusion after dilution:

M.V.I.-12 Pharmacy Bulk Package: consists of two pharmacy bulk vials which must be mixed prior to use. The mixed solution will provide ten 10 mL single doses which must be diluted prior to intravenous administration. Pharmacy bulk package of M.V.I.-12 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 (2.3)].

Do not administer M.V.I.-12 as a direct, undiluted intravenous injection as it may cause dizziness, faintness, and tissue irritation.

2.2 Dosage Information

The recommended daily dosage volume is 10 mL. One daily dose (10 mL) is diluted by adding directly to a specified volume of an intravenous fluid [see Dosage and Administration (2.3)].

Patients with multiple vitamin deficiencies or with increased vitamin requirements may need multiple daily dosages as indicated or additional doses of individual vitamins.

2.3 Preparation and Administration Instructions

• Handling of M.V.I.-12 solution, including preparation of the pharmacy bulk pack, should be restricted to a suitable work area, such as a laminar flow hood (or an equivalent clean air compounding area).
• Aseptically transfer the contents of Vial 1 (50 mL) into Vial 2 (50 mL). The mixed solution (100 mL) will provide ten 10 mL single doses to patients in a pharmacy admixture program.
• 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 closure system has been penetrated, complete dispensing from the pharmacy bulk vial within 4 hours. Mixed solution may be stored for up to 4 hours refrigerated.
• Discard unused portion.
• Visually inspect for particulate matter and discoloration prior to administration.
• Utilizing a suitable sterile automated compounding device or dispensing pin for accuracy, aseptically transfer each 10 mL dose into a plastic or glass bottle containing at least 500 to 1,000 mL intravenous parenteral nutrition solution containing dextrose or saline.
• After M.V.I.-12 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 M.V.I.-12, particularly A, D and riboflavin, are light sensitive.

2.4 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.

2.5 Drug Incompatibilities

• M.V.I.-12 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, and chlorothiazide sodium.
• Folic acid is unstable in the presence of calcium salts such as calcium gluconate.
• Vitamin A and thiamine in M.V.I.-12 may react with bisulfite solutions such as sodium bisulfite or vitamin K bisulfate. Patients should be monitored for vitamin A and thiamine deficiencies. Do not add M.V.I.-12 directly to intravenous fat emulsions.
• Consult appropriate references for listings of physical and chemical compatibility of solutions and drugs with M.V.I.-12. In such circumstances, admixture or Y-site administration with M.V.I.-12 should be avoided.

5.1 Aluminum Toxicity

M.V.I.-12 contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration in patients with renal impairment. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 micrograms per kg per 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 monitor periodically aluminum levels with prolonged parenteral administration of M.V.I.-12.

5.2 Risk of Low Vitamin A Levels

Vitamin A may adhere to plastic, resulting in lower vitamin A concentrations after administration of M.V.I.-12. Therefore, blood vitamin concentrations should be periodically monitored and the administration of additional therapeutic doses of Vitamin A may be required.

5.3 Allergic Reactions to Thiamine

Allergic reactions such as urticaria, periorbital and digital edema, have been reported following intravenous administration of thiamine, which is found in M.V.I.-12. There have been rare reports of anaphylactoid reactions following intravenous doses of thiamine. No fatal anaphylactoid reactions associated with M.V.I.-12 have been reported.

5.4 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 diseases with vitamin A, an ingredient found in M.V.I.-12, should be undertaken with caution [see Use in Specific Populations (8.6 and 8.7)]. Blood levels of Vitamin A should be monitored periodically.

5.5 Interference with Diagnosis of Megaloblastic Anemia Patients

Avoid the use of M.V.I.-12 in patients with suspected or diagnosed megaloblastic anemia prior to blood sampling for the detection of the folic acid and cyanocobalamin deficiencies. M.V.I.-12 contains folic acid and cyanocobalamin which can mask serum deficits of folic acid and cyanocobalamin in patients with megaloblastic anemia.

5.6 Potential to Develop Vitamin Deficiencies or Excesses

In patients receiving parenteral multivitamins, such as with M.V.I.-12, blood vitamin concentrations should be periodically monitored to determine if vitamin deficiencies or excesses are developing. M.V.I.-12 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)].

5.7 Interference with Urine Glucose Testing

M.V.I.-12 contains Vitamin C which is also known as ascorbic acid. Ascorbic acid in the urine may cause false negative urine glucose determinations.

7.1 Effect of M.V.I.-12 on Other Drugs

7.2 Effect of Other Drugs on M.V.I.-12

8.1 Pregnancy

M.V.I.-12 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 nonpregnant women.

8.3 Nursing Mothers

M.V.I.-12 has not been studied in lactating women. Lactating women should follow the U.S. Recommended Daily Allowances for their condition, because their vitamin requirements may exceed those of nonlactating women. Caution should be exercised when M.V.I.-12 is administered to a nursing woman.

8.4 Pediatric Use

M.V.I.-12 is indicated for the prevention of vitamin deficiency in pediatric patients age 11 years and above on warfarin anticoagulant therapy receiving parenteral nutrition. Safety and effectiveness of M.V.I.-12 in pediatric patients below the age of 11 years have not been established.

8.5. Geriatric Use

Reported clinical experience has not identified differences in responses between the elderly and younger patients.

8.6 Renal Impairment

M.V.I.-12 has not been studied in patients with renal impairment. Monitor renal function, calcium, phosphorus and vitamin A levels in patients with renal impairment [see Warning and Precautions (5.1, 5.4)].

8.7 Hepatic Impairment

M.V.I.-12 has not been studied in patients with hepatic impairment. Monitor vitamin A level in patients with liver disease or high alcohol consumption [see Warning and Precautions (5.4)].

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity and fertility studies were not performed.

M.V.I.-12 Pharmacy Bulk Package

Vial 1 is an amber vial containing a clear, amber to orange colored solution. Vial 2 is an amber vial containing a clear to light straw colored solution. Mix contents of Vial 1 and Vial 2 to provide ten 10 mL single doses [see Dosage and Administration (2.3)].

See Description section for vitamin strengths [see Description (11)].

Minimize the exposure of M.V.I.-12 to the light, because vitamins A, D and riboflavin are light sensitive.

Store at 2–8°C (36–46°F).