FDA Label for Dodex Injectable

Description:

Dodex ^® Injectable (Cyanocobalamin Injection, USP) is a sterile solution of cyanocobalamin for intramuscular or subcutaneous injection. Each mL contains 1000 mcg cyanocobalamin.

Each vial also contains Sodium Chloride, 0.4% and Sodium Acetate, 0.04%. Benzyl Alcohol, 1.5%, is present as a preservative and Water for Injection q.s. Glacial acetic acid may has 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 B ₁₂ coenzymes are very unstable in light.

The chemical name is 5,6-dimethyl-benzimidazolyl cyanocobamide; the molecular formula is C ₆₃H ₈₈CoN ₁₄O ₁₄P. The cobalt content is 4.34%. The molecular weight is 1355.39.

The structural formula is represented below.

Structural Formula - cyanocobalamin structure

Clinical Pharmacology:

Vitamin B ₁₂ 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 B ₁₂ is transported via specific B ₁₂ binding proteins, transcobalamin I and II to the various tissues. The liver is the main organ for vitamin B ₁₂ storage.

Within 48 hours after injection of 100 or 1000 mcg of vitamin B ₁₂, 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 B ₁₂ 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 B ₁₂ prevents progression of neurologic damage.

The average diet supplies about 5 to 15 mcg/day of vitamin B ₁₂ in a protein-bound form that is available for absorption after normal digestion. Vitamin B ₁₂ 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 B ₁₂ is bound to intrinsic factor during transit through the stomach; separation occurs in the terminal ileum in the presence of calcium, and vitamin B ₁₂ 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 B ₁₂.

Cyanocobalamin is the most widely used form of vitamin B ₁₂, 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.

Indications And Usage:

Cyanocobalamin is indicated for vitamin B ₁₂ 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 B ₁₂ 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 B ₁₂ absorption test ( Schilling test).

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

Overdosage:

No overdosage has been reported with this drug.

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.

How Supplied:

Dodex ^® Injectable (Cyanocobalamin Injection, USP 1,000 mcg/mL) is supplied as follows:

NDC 16729-533-63           1 mL Multiple Dose Vial            Boxes of 1

NDC 16729-533-08           1 mL Multiple Dose Vial            Boxes of 25

NDC 16729-533-03           10 mL Multiple Dose Vial          Boxes of 1

NDC 16729-533-10           30 mL Multiple Dose Vial          Boxes of 1

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

PROTECT FROM LIGHT.

Use only if solution is clear and seal intact.

Manufactured for:
Accord Healthcare, Inc.,
Durham, NC 27703, USA.

Manufactured by:
Intas Pharmaceuticals Limited,
Plot No.: 457, 458, Village – Matoda,
Bavla Road, Ta.- Sanand,
Dist.- Ahmedabad – 382 210, India.

Revised: 9/2020

10 4292 1 6007613

Principal Display Panel - 1 Ml Vial Label

NDC 16729-533-63
Sterile

Dodex ^® Injectable
Cyanocobalamin Injection, USP

1000 mcg/mL

For IM or SC Use Only

Contains Benzyl Alcohol as a Preservative

For IM or SC Use Only

1 mL Vial

Rx only

PRINCIPAL DISPLAY PANEL - 1 mL vial label - cyanocobalamin 1ml vial label

Principal Display Panel - 1 Ml Vial Carton

NDC 16729-533-63
Sterile

Dodex ^® Injectable
Cyanocobalamin Injection, USP

1000 mcg/mL

For IM or SC Use Only

Contains Benzyl Alcohol as a Preservative

For IM or SC Use Only

1 mL Vial

Rx only

PRINCIPAL DISPLAY PANEL - 1 mL vial Carton - cyanocobalamin 1ml vial carton

Principal Display Panel - 25 X 1 Ml Vial Carton

NDC 16729-533-08
Sterile

Dodex ^® Injectable
Cyanocobalamin Injection, USP

1000 mcg/mL

For IM or SC Use Only

Contains Benzyl Alcohol as a Preservative

For IM or SC Use Only

25 x 1 mL Vial

Rx only

PRINCIPAL DISPLAY PANEL - 25 X 1 mL vial Carton - cyanocobalamin 25x1ml vial carton

Principal Display Panel - 10 Ml Vial Label

NDC 16729-533-03
Sterile

Dodex ^® Injectable
Cyanocobalamin Injection, USP

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

For IM or SC Use Only

Contains Benzyl Alcohol as a Preservative

For IM or SC Use Only

10 mL Multiple-Dose Vial

Rx only

PRINCIPAL DISPLAY PANEL - 10 mL vial label - cyanocobalamin 10ml vial label

Principal Display Panel - 10 Ml Vial Carton

NDC 16729-533-03
Sterile

Dodex ^® Injectable
Cyanocobalamin Injection, USP

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

For IM or SC Use Only

Contains Benzyl Alcohol as a Preservative

For IM or SC Use Only

10 mL Multiple-Dose Vial

Rx only

PRINCIPAL DISPLAY PANEL - 10 mL vial carton - cyanocobalamin 10ml vial carton

Principal Display Panel - 30 Ml Vial Label

NDC 16729-533-10
Sterile

Dodex ^® Injectable
Cyanocobalamin Injection, USP

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

For Intramuscular or Subcutaneous Use Only

Contains Benzyl Alcohol as a Preservative

30 mL Multiple-Dose Vial

Rx only

PRINCIPAL DISPLAY PANEL - 30 mL vial label - cyanocobalamin 30ml vial label

Principal Display Panel - 30 Ml Vial Carton

NDC 16729-533-10
Sterile

Dodex ^® Injectable
Cyanocobalamin Injection, USP

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

For Intramuscular or Subcutaneous Use Only

Contains Benzyl Alcohol as a Preservative

30 mL Multiple-Dose Vial

Rx only

PRINCIPAL DISPLAY PANEL - 30 mL vial carton - cyanocobalamin 30ml vial carton