1 INDICATIONS AND USAGE Cyanocobalamin Nasal Spray is indicated for: Vitamin B12 maintenance therapy in adult patients with pernicious anemia who are in remission following intramuscular vitamin B12 therapy and who have no nervous system involvement Treatment of adult patients with dietary, drug-induced, or malabsorption-related vitamin B12 deficiency not due to pernicious anemia Prevention of vitamin B12 deficiency in adult patients with vitamin B12 requirements in excess of normal Limitations of Use: Cyanocobalamin Nasal Spray should not be used for the vitamin B12 absorption test (Schilling test).

In patients with correctible or temporary causes of vitamin B12 deficiency, the benefit of continued long term use of Cyanocobalamin Nasal Spray following adequate correction of vitamin B12 deficiency and underlying disease has not been established.

The effectiveness of Cyanocobalamin Nasal Spray in patients with active symptoms of nasal congestion, allergic rhinitis or upper respiratory infection has not been determined.

Treatment with Cyanocobalamin Nasal Spray should be deferred until symptoms have subsided.

Cyanocobalamin Nasal Spray is a vitamin B12 indicated for: Vitamin B12 maintenance therapy in adult patients with pernicious anemia who are in remission following intramuscular vitamin B12 therapy and who have no nervous system involvement Treatment of adult patients with dietary, drug-induced, or malabsorption related vitamin B12 deficiency not due to pernicious anemia Prevention of vitamin B12 deficiency in adult patients with vitamin B12 requirements in excess of normal Limitations of Use: Should not be used for the vitamin B12 absorption test (Schilling test).

In patients with correctible or temporary causes of vitamin B12 deficiency the benefit of continued long-term use following correction of vitamin B12 deficiency and underlying disease has not been established.

In patients with active symptoms of nasal congestion, allergic rhinitis or upper respiratory infection effectiveness has not been established.

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Severe Optic Atrophy in Patients with Leber's Disease [ see Warnings and Precautions (5.1) ].

Anaphylactic Reactions [ see Warnings and Precautions (5.2) ].

Hypokalemia and Thrombocytosis Due to Intense Treatment of Megaloblastic Anemia [ see Warnings and Precautions (5.4) ].

The most common adverse reactions (≥ 4%) were infection, headache, glossitis, paresthesia, asthenia, nausea and rhinitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc., at 1-866-403-7592 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The adverse reactions described in Table 1 below are based on data from an eight week cross over trial in which vitamin B12 deficient patients in hematologic remission received one vitamin B12 intramuscular injection (N=25) and then received once weekly intranasal administration of another nasal cyanocobalamin formulation (N=24) for 4 weeks.

Table 1.

Adverse Reactions Following Intranasal or Intramuscular Administration of Cyanocobalamin In Vitamin B12 Deficient Patients in Hematologic Remission Adverse Reaction Number of Patients (%) Another Cyanocobalamin Nasal Formulation, 500 mcg (n=24) Intramuscular Cyanocobalamin*, 100 mcg (n=25) Infectiona 3 (13) 3 (12) Headache 1 (4) 5 (20) Asthenia 1 (4) 4 (16) Nausea 1 (4) 1 (4) Glossitis 1 (4) 0 (0) Paresthesia 1 (4) 1 (4) Rhinitis 1 (4) 2 (8) a Sore throat, common cold * The data are not an adequate basis for comparison of rates between the study drug and the active control