CYANOCOBALAMIN

INDICATIONS AND USAGE Cyanocobalamin is indicated for vitamin B12 deficiencies due to malabsorption which may be associated with the following conditions: Addisonian (pernicious) anemia Gastrointestinal pathology, dysfunction, or surgery, including gluten enteropathy or sprue, small bowel bacteria overgrowth, total or partial gastrectomy Fish tapeworm infestation Malignancy of pancreas or bowel Folic acid deficiency It may be possible to treat the underlying disease by surgical correction of anatomic lesions leading to small bowel bacterial overgrowth, expulsion of fish tapeworm, discontinuation of drugs leading to vitamin malabsorption (see Drug Interactions ), use of a gluten-free diet in nontropical sprue, or administration of antibiotics in tropical sprue. Such measures remove the need for long-term administration of cyanocobalamin. Requirements of vitamin B12 in excess of normal (due to pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage, malignancy, hepatic and renal disease) can usually be met with oral supplementation. Cyanocobalamin Injection, USP is also suitable for the vitamin B12 absorption test (Schilling test).

DOSAGE AND ADMINISTRATION Avoid using the intravenous route. Use of this product intravenously will result in almost all of the vitamin being lost in the urine. Pernicious Anemia Parenteral vitamin B12 is the recommended treatment and will be required for the remainder of the patient's life. The oral form is not dependable. A dose of 100 mcg daily for 6 or 7 days should be administered by intramuscular or deep subcutaneous injection. If there is clinical improvement and if a reticulocyte response is observed, the same amount may be given on alternate days for seven doses, then every 3 to 4 days for another 2 to 3 weeks. By this time hematologic values should have become normal. This regimen should be followed by 100 mcg monthly for life. Folic acid should be administered concomitantly if needed. Patients with Normal Intestinal Absorption Where the oral route is not deemed adequate, initial treatment similar to that for patients with pernicious anemia may be indicated depending on the severity of the deficiency. Chronic treatment should be with an oral B12 preparation. If other vitamin deficiencies are present, they should be treated. Schilling Test The flushing dose is 1000 mcg. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

CONTRAINDICATIONS Sensitivity to cobalt and/or vitamin B12 is a contraindication.

WARNINGS Patients with early Leber's disease (hereditary optic nerve atrophy) who were treated with cyanocobalamin suffered severe and swift optic atrophy. Hypokalemia and sudden death may occur in severe megaloblastic anemia which is treated intensely. Anaphylactic shock and death have been reported after parenteral vitamin B12 administration. An intradermal test dose is recommended before Cyanocobalamin Injection, USP is administered to patients suspected of being sensitive to this drug. This product contains Benzyl Alcohol. Benzyl Alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants. This product 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 solutions, 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.

ADVERSE REACTIONS Generalized: Anaphylactic shock and death have been reported with administration of parenteral vitamin B12 (see WARNINGS ). Cardiovascular: Pulmonary edema and congestive heart failure early in treatment; peripheral vascular thrombosis. Hematological: Polycythemia vera Gastrointestinal: Mild transient diarrhea Dermatological: Itching; transitory exanthema Miscellaneous: Feeling of swelling of entire body To report SUSPECTED ADVERSE REACTIONS, contact Vitruvias Therapeutics at 1-844-451-5944 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pregnancy Teratogenic Effects Pregnancy Category C Adequate and well-controlled studies have not been done in pregnant women. However, vitamin B12 is an essential vitamin and requirements are increased during pregnancy. Amounts of vitamin B12 that are recommended by the Food and Nutrition Board, National Academy of Science-National Research Council for pregnant women (4 mcg daily) should be consumed during pregnancy.