Cynovit

Approved Indications:

• Vitamin B12 Deficiency:
• Due to pernicious anemia (autoimmune-related)
• Malabsorption syndromes (e.g., celiac disease, Crohn’s disease)
• Post-gastrectomy or bariatric surgery
• Intestinal resection or atrophy
• Pancreatic insufficiency
• Megaloblastic Anemia: Due to confirmed B12 deficiency.
• Neurological disorders associated with B12 deficiency: Peripheral neuropathy, subacute combined degeneration of the spinal cord.
• B12 Deficiency due to drug use: Long-term use of metformin, proton pump inhibitors, H2-blockers.
• B12 Deficiency due to dietary insufficiency: Vegan or vegetarian diets without adequate B12 intake.
• Maintenance therapy after initial correction of deficiency.

Clinically Accepted Off-label Uses:

• Fatigue or cognitive impairment in elderly with low-normal B12 levels.
• Supportive therapy in cyanide poisoning (as hydroxocobalamin is preferred but cyanocobalamin may be used in limited cases).
• Adjunct in optic neuropathies such as tobacco-alcohol amblyopia.
• Adjunctive treatment in homocystinuria to lower homocysteine levels in B12-responsive types.

Routes of Administration:
• Oral
• Intramuscular (IM)
• Subcutaneous (SC)
• Intranasal (specific formulations)

For Vitamin B12 Deficiency (including Pernicious Anemia):

• Initial therapy:
• IM or deep SC: 100 mcg to 1000 mcg once daily or every other day for 1–2 weeks until improvement.
• Neurological involvement present:
• IM: 1000 mcg daily for 1 week, then weekly for 4 weeks.
• Maintenance:
• IM or SC: 1000 mcg once monthly
• Oral: 1000–2000 mcg daily, especially in those without absorption defects.

For Megaloblastic Anemia:

• IM/SC: 1000 mcg every day for 7 days, then weekly for 1 month, then monthly for maintenance.

For Dietary Deficiency (e.g., Vegan):

• Oral: 250–1000 mcg daily

Intranasal (Maintenance Only):

• 500 mcg intranasally once weekly

Pediatrics:

• Doses vary by age and indication. Typical pediatric dose:
• IM/SC: 5–25 mcg/day for 7–14 days, followed by weekly/monthly doses as needed.

Elderly:

• No dose adjustment; may require long-term supplementation.

Renal/Hepatic Impairment:

• No adjustment needed; cyanocobalamin is generally safe.

Cyanocobalamin is a synthetic form of vitamin B12, essential for DNA synthesis, red blood cell maturation, and neurological function. It serves as a cofactor for two enzymatic reactions: (1) the conversion of methylmalonyl-CoA to succinyl-CoA (vital in fatty acid and energy metabolism) and (2) the conversion of homocysteine to methionine, which is essential for methylation reactions. These functions are critical in hematopoiesis, neuronal myelination, and cell replication. Cyanocobalamin must first be converted in the body to its active forms—methylcobalamin and adenosylcobalamin—to exert these physiological effects.

• Absorption:
• Oral absorption requires intrinsic factor and intact ileum.
• Approximately 1% of oral dose is absorbed via passive diffusion regardless of intrinsic factor.
• Bioavailability:
• Oral: ~5–10% (varies with GI function)
• IM: 100% (bypasses GI absorption)
• Distribution:
• Widely distributed in tissues, especially liver, bone marrow, and kidneys.
• Binds to transcobalamin II for cellular uptake.
• Metabolism:
• Converted to active forms: methylcobalamin and adenosylcobalamin in liver and tissues.
• Elimination:
• Excreted primarily via urine; small amounts via bile.
• Enterohepatic recirculation helps conserve body stores.
• Half-life:
• Plasma half-life: ~6 days
• Hepatic storage half-life: several months

• Pregnancy:
  FDA Pregnancy Category C (older classification). Cyanocobalamin is considered safe in recommended doses during pregnancy. B12 requirements increase in pregnancy due to fetal growth.
• Lactation:
  Cyanocobalamin is excreted into breast milk. It is safe during breastfeeding, and supplementation may be necessary in deficient mothers to support infant development.
• Caution:
  Avoid high pharmacologic doses unless clinically indicated; consult a healthcare provider.

• Primary Class: Hematinic / Vitamin Supplement
• Sub-Class: Water-soluble Vitamin B12 Analog

• Known hypersensitivity to cyanocobalamin or cobalt
• Early hereditary optic nerve atrophy (Leber’s disease)—may worsen condition
• Hypokalemia uncorrected prior to initiation of therapy (caution in severe anemia)

• Hypokalemia Risk: Rapid correction of megaloblastic anemia may cause sudden hypokalemia and cardiac arrhythmias.
• Monitor hematologic response: Especially in severe B12 deficiency with neurological symptoms.
• Unmasking of polycythemia vera: May occur with hematologic response.
• Injection site reactions or anaphylaxis (rare but reported).
• Intranasal forms: Avoid in patients with nasal congestion or rhinitis.
• Do not use IV route—not indicated or safe.

Common:

• Injection site reactions: Pain, redness, or swelling
• Gastrointestinal: Nausea, diarrhea
• Neurologic: Headache, dizziness

Less Common:

• Allergic reactions: Rash, itching
• General: Fatigue, arthralgia, fever

Rare but Serious:

• Anaphylaxis (especially after injection)
• Hypokalemia (due to rapid cell uptake during correction of anemia)
• Thrombocytosis or polycythemia
• Peripheral vascular thrombosis (rare, usually in high doses)

• Chloramphenicol: May antagonize hematologic response to B12 therapy.
• Proton Pump Inhibitors / H2 Antagonists: Reduce gastric acid needed for B12 release, impairing absorption.
• Metformin: Long-term use reduces B12 absorption from the GI tract.
• Nitrous oxide anesthesia: Can inactivate vitamin B12 and worsen deficiency symptoms.
• Alcohol abuse: May impair absorption and hepatic metabolism of B12.

Enzyme System Involvement:
No significant CYP450 metabolism; drug interactions are largely due to absorption interference rather than metabolic induction or inhibition.

• Recent focus on early screening of B12 deficiency in:
• Elderly
• Diabetic patients on long-term metformin
• Vegans and pregnant women
• WHO and NICE emphasize prompt parenteral correction in neurological involvement.
• Oral high-dose therapy (1000–2000 mcg/day) is now accepted in non-malabsorptive deficiency.
• Intranasal formulations added for maintenance, avoiding injection.

• Temperature: Store between 15°C and 25°C (59°F to 77°F).
• Protection: Keep away from excessive heat, light, and moisture.
• Handling:
• Protect ampoules or vials from light.
• Do not freeze.
• Shake oral liquid gently before use.
• Shelf life: Follow manufacturer guidelines; typically 24 months unopened.