July 22, 1997

Dear Healthcare Professional:

Zeneca Pharmaceuticals would like to bring to your attention changes to the enclosed package insert for ACCOLATE (zarfirlukast) Tablets. Since ACCOLATE was cleared by the FDA in September 1996, it has been prescribed to approximately 250,000 patients in the United States for the prophylaxis and chronic treatment of asthma in patients 12 years and older.

The reduction of the oral steroid dose in some patients on ACCOLATE therapy has been followed in rare cases by the occurrence of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes presenting as Churg Strauss Syndrome¹, a systemic eosinophilic vasculitis. Treatment can consist of reinstituting systemic steroids; sometimes other agents such as cyclophosphamide are added. A causal relationship with ACCOLATE has not been established.

In order to communicate this important information to healthcare professionals, the PRECAUTIONS and ADVERSE REACTIONS sections of the revised package insert for ACCOLATE includes the following changes:

PRECAUTIONS-Eosinophilic Conditions: The reduction of the oral steroid dose, in some patients on ACCOLATE therapy, has been followed in rare cases by the occurrence of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes presenting as Churg Strauss Syndrome, a systemic eosinophilic vasculitis. Although a causal relationship with ACCOLATE has not been established, caution is required when oral steroid reduction is being considered. (See ADVERSE REACTIONS).

ADVERSE REACTIONS
The reduction of oral steroid dose, in some patients on ACCOLATE therapy has been followed in rare cases by the occurrence of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes presenting as Churg Strauss Syndrome, a systemic eosinophilic vasculitis. A causal relationship with ACCOLATE has not been established. (See PRECAUTIONS-Eosinophilic Conditions).

Another change to the ADVERSE REACTIONS section has also been included in the revised package insert. Please take the time to read the enclosed revised package insert. Questions from healthcare professionals may be directed to our Medical Information Department in Wilmington, Delaware between the hours of 8:15 a.m. and 4:30 p.m. E.S.T. at (302) 886-8000.

You can also assist us in maintaining the safety of ACCOLATE by reporting all adverse events to Zeneca's Drug Safety and Epidemiology Department at (302) 886-3000 or to the FDA MedWatch program by phone 1-800-FDA-1088, by FAX at 1-800-FDA-0178, or by mail at MedWatch, HF-2, 5600 Fishers Lane, Rockville, MD 20857.

Sincerely,

Gerard T. Kennealey, MD
Vice President, Medical Affairs

Enclosure - Revised package insert

¹ Masi, AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY, Lightfoot RW, Jr., McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifler NJ: The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss Syndrome (allergic granulomatosis and angiitis), Arthritis Rheum 1990, 33:8:pp. 1094-1100.

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