Nascobal

 Testing and Other ConsiderationsPrior to Dosing

Prior to treatment, obtain hematocrit, reticulocyte count, vitamin B12, folate, and iron levels [see Dosage and Administration (2.4)].  Consider the potential for concomitant drugs to interfere with vitamin B12 and folate diagnostic blood assays [see Drug Interactions (7)]. 

In patients with suspected cobalamin hypersensitivity, consider administering an intradermal test dose of parenteral vitamin B12 prior to use of NASCOBAL [see Warnings and Precautions (5.2)]. 

  Recommended Dosage

The recommended initial dose of NASCOBAL is one spray (500 mcg) administered in ONE nostril once weekly. Administer NASCOBAL at least one hour before or one hour after ingestion of hot foods or liquids since hot foods may cause nasal secretions and a resulting loss of medication. Defer use of NASCOBAL in patients with nasal congestion, allergic rhinitis, or upper respiratory infections until after symptoms have subsided.

  Monitoring, Dosage Modifications, andTreatment Duration

Monitoring for Response and Safety

Monitor serum B12 levels periodically during therapy to establish adequacy of therapy.  Obtain a serum B12 level and peripheral blood count one month after treatment initiation, then subsequently at intervals of 3 to 6 months [see Warnings and Precautions (5.3)].

Dosage Modifications

If serum levels of B12 decline after one month of treatment with NASCOBAL, consider increasing the dose.    Assess serum B12 level one month after each dose adjustment.  If serum B12 levels are persistently low, consider alternative therapy (e.g., intramuscular or subcutaneous vitamin B12 therapy).

Treatment Duration

In patients whose underlying cause of vitamin B12 deficiency has been corrected and are deemed no longer at risk for vitamin B12 deficiency, discontinue NASCOBAL.  The safety and effectiveness of continued long-term use in these individuals has not been established.

In patients with pernicious anemia, continue appropriate vitamin B12 treatment indefinitely. 

  Administration of NASCOBAL withOther Therapy

NASCOBAL should be administered with other therapy(ies) in:

• Patients with concurrent folate and vitamin B12 deficiency:Administer folic acid in addition to NASCOBAL
• Patients with concurrent iron and vitamin B12 deficiency:Administer iron in addition to NASCOBAL
• Patients with correctible causes of vitamin B12 deficiency:Consider measures to treat the underlying condition associated with vitamin B12 deficiency in addition to treatment with NASCOBAL

Pregnancy

Risk Summary

The limited available data on NASCOBAL in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes.  However, vitamin B12 is an essential vitamin and requirements are increased during pregnancy.

Animal reproduction studies have not been conducted with vitamin B12.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

Risk Summary

Vitamin B12 is present in the milk of lactating women in concentrations which approximate the mother’s vitamin B12 blood level. Vitamin B12 does not appear to pose more than a minimal risk to breastfeeding children.

Pediatric Use

Safety and effectiveness have not been established in pediatric patients.

Geriatric Use

Clinical studies of NASCOBAL did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

 Severe Optic Atrophy in Patients with Leber’s Disease

Patients with early Leber’s disease (hereditary optic nerve atrophy) who were treated with vitamin B12 suffered severe and swift optic atrophy. Cyanocobalamin products, including NASCOBAL, is not recommended for use in patients with Leber’s optic atrophy. For patients with Leber’s disease requiring vitamin B12, consider alternative therapy (e.g., hydroxocobalamin) for B12 supplementation.

 Anaphylactic Reactions

Anaphylactic shock and death have been reported after parenteral vitamin B12 administration. If patients are to start NASCOBAL before having tolerated cyanocobalamin parenterally, consider administering an intradermal test dose of parenteral vitamin B12 to patients suspected of cyanocobalamin hypersensitivity [see Dosage and Administration (2.1)].

 Masking of Folate Deficiency with Vitamin B12 Use

Doses of vitamin B12 exceeding 10 mcg daily may produce hematologic response in patients with folate deficient megaloblastic anemia and may therefore mask a previously unrecognized folate deficiency. Vitamin B12 is not a substitute for folic acid [see Dosage and Administration (2.4)]. Assess both vitamin B12 and folate levels prior to initiating therapy with vitamin B12, including NASCOBAL, or with folic acid [see Dosage and Administration (2.1)].

 Hypokalemia and Thrombocytosis Due to IntenseTreatment of Megaloblastic Anemia

Hypokalemia and sudden death may occur in severe megaloblastic anemia that is treated intensely with vitamin B12.  Hypokalemia and thrombocytosis can occur upon conversion of severe megaloblastic anemia to normal erythropoiesis with vitamin B12 therapy.  Therefore, serum potassium levels and platelet count should be monitored carefully during therapy [see Dosage and Administration (2.3)]. 

 Unmasking of Polycythemia Vera

Vitamin B12 deficiency may suppress the signs of polycythemia vera. Treatment with vitamin B12 may unmask this condition.  Patients exhibiting clinical or hematologic response consistent with polycythemia vera should be referred for further evaluation.