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, 0.9%. Benzyl Alcohol, 1.5%, is present as a preservative. Sodium hydroxide and/or hydrochloric acid 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 C₆₃H₈₈C₀N₁₄O₁₄P. The cobalt content is 4.34%. The molecular weight is 1355.39.

The structural formula is represented below.

Last updated on RxList: 10/23/2008

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 B₁₂absorption test (Schilling test).

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.

Cyanocobalamin Injection, USP 1000 mcg/mL

NDC 0517-0031-25   1 mL 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 Individually packaged
NDC 0517-0130-05   30 mL Multiple Dose Vial     Boxes of 5

Store at controlled room temperature 15°-30°C (59°-86°F) (See USP).

PROTECT THE PRODUCT FROM LIGHT.

American Regent, Inc.Shirley, NY 11967. FDA Rev date: 9/23/2003

Last updated on RxList: 10/23/2008

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

Drug/Laboratory Test Interactions: Persons taking most antibiotics, methotrexate and pyrimethamine invalidate folic acid and vitamin B₁₂ diagnostic blood assays.

Colchicine para-aminosalicylic acid and heavy alcohol intake for longer than 2 weeks may produce malabsorption of vitamin B₁₂.

Last updated on RxList: 10/23/2008

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.

General Precautions

Vitamin B₁₂ 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 B₁₂ deficiency. Neurologic manifestations will not be prevented with folic acid, and if not treated with vitamin B₁₂, 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.

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 B₁₂, 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.

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

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.

Nursing Mothers

Vitamin B₁₂ is known to be excreted in human milk. Amounts of vitamin B₁₂ 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.

Last updated on RxList: 10/23/2008

No overdosage has been reported with this drug.

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

Last updated on RxList: 10/23/2008

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 1000 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.

Last updated on RxList: 10/23/2008

Patients with pernicious anemia should be informed that they will require monthly injections of vitamin B₁₂ 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 B₁₂, 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 B₁₂. Patients following such a diet, should be advised to take oral vitamin B₁₂ regularly. The need for vitamin B₁₂ 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.

Last updated on RxList: 10/23/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CYANOCOBALAMIN - INJECTION

(SYE-an-oh-koe-BAL-a-min)

COMMON BRAND NAME(S): Cobal, Cyanoject, Cyomin, Vibal, Vitamin B-12

USES: Cyanocobalamin is a man-made form of vitamin B12 used to treat low levels (deficiency) of this vitamin. Vitamin B12 helps your body use fat and carbohydrates for energy and make new protein. It is also important for normal blood, cells, and nerves. Most people get enough vitamin B12 in their diet, but a deficiency may occur in certain health conditions (e.g., poor nutrition, stomach/intestinal problems, infection, cancer). Serious vitamin B12 deficiency may result in anemia, stomach problems, and nerve damage.

HOW TO USE: Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid.

This medication is given by injection into a muscle or under the skin as directed by your doctor.

Dosage is based on your medical condition and response to treatment. Injections may be given daily when you first start treatment. Certain medical conditions (e.g., pernicious anemia) may require you to continue receiving injections every month.

Learn how to store and discard needles and medical supplies safely. Consult your pharmacist.

SIDE EFFECTS: Pain/redness at the injection site, mild diarrhea, itching, or a feeling of swelling all over the body may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This medication may cause low potassium levels in the blood (hypokalemia). Tell your doctor immediately if any of these unlikely but serious side effects occur: muscle cramps, weakness, irregular heartbeat.

People who have a rare blood disorder (polycythemia vera) may infrequently have symptoms related to this disorder while taking cyanocobalamin. Seek immediate medical attention if any of these rare but very serious symptoms occur: chest pain (especially with shortness of breath), weakness on one side of the body, sudden vision changes, slurred speech.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the tongue/lips/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using cyanocobalamin, tell your doctor or pharmacist if you are allergic to it; or to cobalt; or if you have any other allergies. Your doctor may recommend that you receive a smaller test dose before starting your regular dose. Consult your doctor or pharmacist for more information.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low potassium blood levels (hypokalemia), gout, a certain blood disorder (polycythemia vera), a certain eye disease (Leber's disease), other vitamin/mineral deficiencies (especially folic acid and iron).

This product may contain aluminum, which can infrequently build up to dangerous levels in the body. The risk may be increased if this product is used for an extended time, especially in newborns or in people with kidney disease. Tell your doctor immediately if you notice any symptoms of too much aluminum in the body such as muscle weakness, bone pain, or mental changes.

A preservative (benzyl alcohol) that might be found in this product can infrequently cause serious (sometimes fatal) problems if given in large amounts (more than 100 milligrams per kilogram daily) to an infant during the first months of life. The risk is also greater with low-birth-weight infants. Symptoms include sudden gasping, low blood pressure, or very slow heartbeat. If you notice any of these symptoms in your newborn, report them to the doctor immediately. If possible, a preservative-free product should be used when treating newborns.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Based on information from related drugs, this medication may pass into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: drugs that may affect blood cell production (e.g., chloramphenicol, anti-cancer drugs, HIV drugs), other vitamins/nutritional supplements (especially folic acid).

Certain other drugs may interfere with laboratory tests for vitamin B12 levels, possibly causing false test results. Tell laboratory personnel and all your doctors if you take any of the following: anti-infective drugs (e.g., amoxicillin, erythromycin), methotrexate, pyrimethamine.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: Overdose with this medication is very unlikely. However, if overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., serum potassium levels, complete blood count, hematocrit, vitamin B12 levels) should be performed to monitor your progress or check for side effects. Consult your doctor for more details.

This product is not a substitute for a proper diet. Remember that it is best to get your vitamins from healthy foods. Vitamin B12 is commonly found in many foods from animals, especially liver, kidney, fish and shellfish, meat, and dairy foods.

MISSED DOSE: If you miss a dose, contact your doctor to establish a new dosing schedule.

STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not freeze. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.