Cyanocobalamin

INDICATIONS & 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 PRECAUTIONS- 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 ( DOSAGE & ADMINISTRATION- 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 B 12 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 six or seven 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 three to four days for another two to three 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 B 12 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.

Pernicious Anemia Parenteral Vitamin B 12 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 six or seven 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 three to four days for another two to three 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 B 12 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 B 12 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 B 12 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 B 12 (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.

Generalized Anaphylactic shock and death have been reported with administration of parenteral Vitamin B 12 (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.

DESCRIPTION Cyanocobalamin Injection, USP is a sterile solution of cyanocobalamin for intramuscular or subcutaneous injection. Each mL contains 1,000 mcg cyanocobalamin. Each vial also contains Sodium Chloride USP, 0.9%. Benzyl Alcohol NF, 1.5%, is present as a preservative. Dibasic Sodium Phosphate (Heptahydrate) USP 0.05% is present as a buffering agent. Hydrochloric acid NF and/or sodium hydroxide NF may have been added during manufacture to adjust the pH (range 4.5-7.0). Cyanocobalamin appears as crystals or deep red colored, odorless crystalline powder. It is very hygroscopic in the anhydrous form, and sparingly soluble in water (1:80). It is stable to autoclaving for short periods at 121°C. The vitamin B 12 coenzymes are very unstable in light. The chemical name is 5,6-dimethyl-benzimidazolyl cyanocobamide; the molecular formula is C 63 H 88 CoN 14 O 14 P. The cobalt content is 4.35%. The molecular weight is 1355.4. The structural formula is represented below. Image

OVERDOSAGE: No overdosage has been reported with this drug.

HOW SUPPLIED Cyanocobalamin Injection, USP 1,000 mcg/mL Strength(s) Pack NDC 1,000 mcg/mL Carton of 25 Multiple-dose vials 70710-1663-7 1 mL Multiple-dose vial 70710-1663-1 10,000 mcg/10 mL (1,000 mcg/mL) Carton of 10 Multiple-dose vials 70710-1664-6 Carton of 25 Multiple-dose vials 70710-1664-7 10 mL Multiple-dose vial 70710-1664-1 30,000 mcg/30 mL (1,000 mcg/mL) Carton of 1 Multiple-dose vial 70710-1665-1 Carton of 5 Multiple-dose vials 70710-1665-5 30 mL Multiple-dose vial 70710-1665-1 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature). PROTECT THE PRODUCT FROM LIGHT. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Please address medical inquiries to Zydus Pharmaceuticals (USA) Inc. at MedicalAffairs@zydususa.com or Tel.: 1-877-993-8779. Manufactured by: Zydus Lifesciences Ltd. (formerly known as Cadila Healthcare Ltd.) Vadodara, India. Distributed by: Zydus Pharmaceuticals (USA) Inc. Pennington, NJ 08534 Revised: 04/2022