CYANOCOBALAMIN INJECTION, USP

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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, 0.9%. Benzyl Alcohol, 1.5%, is present as a preservative. Hydrochloric acid and/or sodium hydroxide may have been added during manufacture to adjust the pH (range 4.5-7.0).

Cyanocobalamin appears as dark red crystals or as an amorphous or crystalline red 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 B₁₂ coenzymes are very unstable in light.

The chemical name is 5,6-dimethyl-benzimidazolyl cyanocobamide; the molecular formula is C₆₃H₈₈CoN₁₄O₁₄P. The cobalt content is 4.34%. The molecular weight is 1355.39.

The structural formula is represented below.

Vitamin B₁₂ is essential to growth, cell reproduction, hematopoiesis, and nucleoprotein and myelin synthesis.

Cyanocobalamin is quantitatively and rapidly absorbed from intramuscular and subcutaneous sites of injection; the plasma level of the compound reaches its peak within 1 hour after intramuscular injection. Absorbed vitamin B₁₂ is transported via specific B₁₂ binding proteins, transcobalamin I and II to the various tissues. The liver is the main organ for vitamin B₁₂ storage.

Within 48 hours after injection of 100 or 1,000 mcg of vitamin B₁₂, 50 to 98% of the injected dose may appear in the urine. The major portion is excreted within the first eight hours. Intravenous administration results in even more rapid excretion with little opportunity for liver storage.

Gastrointestinal absorption of vitamin B₁₂ depends on the presence of sufficient intrinsic factor and calcium ions. Intrinsic factor deficiency causes pernicious anemia, which may be associated with subacute combined degeneration of the spinal cord. Prompt parenteral administration of vitamin B₁₂ prevents progression of neurologic damage.

The average diet supplies about 5 to 15 mcg/day of vitamin B₁₂ in a protein-bound form that is available for absorption after normal digestion. Vitamin B₁₂ is not present in foods of plant origin, but is abundant in foods of animal origin. In people with normal absorption, deficiencies have been reported only in strict vegetarians who consume no products of animal origin (including no milk products or eggs).

Vitamin B₁₂ is bound to intrinsic factor during transit through the stomach; separation occurs in the terminal ileum in the presence of calcium, and vitamin B₁₂ enters the mucosal cell for absorption. It is then transported by the transcobalamin binding proteins. A small amount (approximately 1% of the total amount ingested) is absorbed by simple diffusion, but this mechanism is adequate only with very large doses. Oral absorption is considered too undependable to rely on in patients with pernicious anemia or other conditions resulting in malabsorption of vitamin B₁₂.

Cyanocobalamin is the most widely used form of vitamin B₁₂, and has hematopoietic activity apparently identical to that of the antianemia factor in purified liver extract. Hydroxycobalamin is equally as effective as cyanocobalamin, and they share the cobalamin molecular structure.

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).

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

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.

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

No overdosage has been reported with this drug.

Avoid using the intravenous route. Use of this product intravenously will result in almost all of the vitamin being lost in the urine.

Cyanocobalamin Injection, USP 1,000 mcg/mL

NDC 0517-0031-25           1 mL Multiple-Dose Vial             Boxes of 25

NDC 0517-0032-25           10 mL Multiple-Dose Vial           Boxes of 25

NDC 0517-0130-01           30 mL Multiple-Dose Vial           Boxes of 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.

IN0031
Rev. 01/2021
MG #10565

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Container

NDC 0517-0031-01

Rx Only

Cyanocobalamin Injection, USP

1,000 mcg/mL

For IM or SC Use Only

1 mL Multiple-Dose Vial

AMERICAN REGENT, INC.
SHIRLEY, NY 11967

1 mL Container Label

Carton

NDC 0517-0031-25

Rx Only

Cyanocobalamin Injection, USP

1,000 mcg/mL

For Intramuscular or Subcutaneous Use Only

25 x 1 mL Multiple-Dose Vials

AMERICAN REGENT, INC.
SHIRLEY, NY 11967

Carton Labeling (1 mL)

Container

NDC 0517-0032-01

CYANOCOBALAMIN INJECTION, USP

10,000 mcg/10 mL

(1,000 mcg/mL)

10 mL MULTIPLE DOSE VIAL

FOR IM OR SC USE ONLY

Rx Only

AMERICAN REGENT, INC.
SHIRLEY, NY 11967

10 mL Container Label

Carton

CYANOCOBALAMIN INJECTION, USP

10,000 mcg/10 mL (1,000 mcg/mL)

NDC 0517-0032-25

25 x 10 mL MULTIPLE DOSE VIALS

FOR INTRAMUSCULAR OR SUBCUTANEOUS USE ONLY

Rx Only

Each mL contains: Cyanocobalamin 1000 mcg, Benzyl Alcohol 1.5%, Sodium Chloride 0.9%, Water for Injection q.s. pH (range 4.5 – 7.0) adjusted with Hydrochloric Acid and/or Sodium Hydroxide. WARNING: PROTECT FROM LIGHT. 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). Directions for Use: See Package Insert.

AMERICAN REGENT, INC.
SHIRLEY, NY 11967

Rev. 5/14

Container

NDC 0517-0130-01

Rx Only

CYANOCOBALAMIN INJECTION, USP

30,000 mcg/30 mL
(1,000 mcg/mL)

30 mL Multiple-Dose Vial

For IM or SC Use Only

AMERICAN REGENT, INC.
SHIRLEY, NY 11967

30 mL Vial Label

Carton

NDC 0517-0130-01

30 mL MULTIPLE DOSE VIAL

CYANOCOBALAMIN INJECTION, USP

30,000 mcg/30 mL (1,000 mcg/mL)

FOR INTRAMUSCULAR OR SUBCUTANEOUS USE ONLY

Rx Only

AMERICAN REGENT, INC.|
SHIRLEY, NY 11967

Carton Labeling (30 mL)