DODEX INJECTABLE- cyanocobalamin injection 
Accord Healthcare, Inc.

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DODEX ® INJECTABLE

CYANOCOBALAMIN INJECTION, USP

Rx Only

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

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:

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.

PRECAUTIONS:

General Precautions: Vitamin B 12 deficiency that is allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord. Doses of folic acid greater than 0.1 mg per day may result in hematologic remission in patients with vitamin B 12 deficiency. Neurologic manifestations will not be prevented with folic acid, and if not treated with vitamin B 12, irreversible damage will result.

Doses of cyanocobalamin exceeding 10 mcg daily may produce hematologic response in patients with folate deficiency. Indiscriminate administration may mask the true diagnosis.

Information for Patients: Patients with pernicious anemia should be informed that they will require monthly injections of vitamin B 12 for the remainder of their lives. Failure to do so will result in return of the anemia and in development of incapacitating and irreversible damage to the nerves of the spinal cord. Also, patients should be warned about the danger of taking folic acid in place of vitamin B 12, because the former may prevent anemia but allow progression of subacute combined degeneration.

A vegetarian diet which contains no animal products (including milk products or eggs) does not supply any vitamin B 12. Patients following such a diet, should be advised to take oral vitamin B 12 regularly. The need for vitamin B 12 is increased by pregnancy and lactation. Deficiency has been recognized in infants of vegetarian mothers who were breast fed, even though the mothers had no symptoms of deficiency at the time.

Laboratory Tests: During the initial treatment of patients with pernicious anemia, serum potassium must be observed closely the first 48 hours and potassium replaced if necessary.

Hematocrit, reticulocyte count, vitamin B 12, folate and iron levels should be obtained prior to treatment. Hematocrit and reticulocyte counts should be repeated daily from the fifth to seventh days of therapy and then frequently until the hematocrit is normal. If folate levels are low, folic acid should also be administered. If reticulocytes have not increased after treatment or if reticulocyte counts do not continue at least twice normal as long as the hematocrit is less than 35%, diagnosis or treatment should be reevaluated. Repeat determinations of iron and folic acid may reveal a complicating illness that might inhibit the response of the marrow.

Patients with pernicious anemia have about 3 times the incidence of carcinoma of the stomach as the general population, so appropriate tests for this condition should be carried out when indicated.

Drug/Laboratory Test Interactions: Persons taking most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B 12 diagnostic blood assays.

Colchicine para-aminosalicylic acid and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B 12.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Long term studies in animals to evaluate carcinogenic potential have not been done. There is no evidence from long-term use in patients with pernicious anemia that cyanocobalamin is carcinogenic. Pernicious anemia is associated with an increased incidence of carcinoma of the stomach, but this is believed to be related to the underlying pathology and not to treatment with cyanocobalamin.

Pregnancy: Teratogenic Effects.
Adequate and well-controlled studies have not been done in pregnant women. However, vitamin B 12 is an essential vitamin and requirements are increased during pregnancy. Amounts of vitamin B 12 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.

Nursing Mothers: Vitamin B 12 is known to be excreted in human milk. Amounts of vitamin B 12 that are recommended by the Food and Nutrition Board, National Academy of Science-National Research Council for lactating women (4 mcg daily) should be consumed during lactation.

Pediatric Use: Intake in children should be in the amount (0.5 to 3 mcg daily) recommended by the Food and Nutrition Board, National Academy of Science-National Research Council.

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.

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 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 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.

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

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

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

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

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

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

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
DODEX INJECTABLE 
cyanocobalamin injection
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:16729-533
Route of AdministrationINTRAMUSCULAR, SUBCUTANEOUS
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
CYANOCOBALAMIN (UNII: P6YC3EG204) (CYANOCOBALAMIN - UNII:P6YC3EG204) CYANOCOBALAMIN1000 ug  in 1 mL
Inactive Ingredients
Ingredient NameStrength
WATER (UNII: 059QF0KO0R)  
BENZYL ALCOHOL (UNII: LKG8494WBH)  
SODIUM CHLORIDE (UNII: 451W47IQ8X)  
SODIUM ACETATE (UNII: 4550K0SC9B)  
ACETIC ACID (UNII: Q40Q9N063P)  
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:16729-533-631 in 1 BOX04/10/2024
11 mL in 1 VIAL, MULTI-DOSE; Type 0: Not a Combination Product
2NDC:16729-533-0825 in 1 BOX04/29/2022
21 mL in 1 VIAL, MULTI-DOSE; Type 0: Not a Combination Product
3NDC:16729-533-031 in 1 BOX04/10/2024
310 mL in 1 VIAL, MULTI-DOSE; Type 0: Not a Combination Product
4NDC:16729-533-101 in 1 BOX04/10/2024
430 mL in 1 VIAL, MULTI-DOSE; Type 0: Not a Combination Product
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA08302204/29/2022
Labeler - Accord Healthcare, Inc. (604222237)
Establishment
NameAddressID/FEIBusiness Operations
Intas Pharmaceuticals Limited725927649manufacture(16729-533) , analysis(16729-533)

Revised: 5/2022
Document Id: de173101-4fa6-a1a6-e053-2a95a90a3023
Set id: 9b1f260b-8796-4eb1-acb2-144588a4214f
Version: 3
Effective Time: 20220503
 
Accord Healthcare, Inc.