Ketotifen in the Prophylaxis of Extrinsic Bronchial Asthma
A Multicenter Controlled Double-Blind Study with a Modified-Release Formulation
Ketotifen (Zaditen or Zasten) is widely used as a prophylactic drug in the treatment of extrinsic bronchial asthma, with the exception of the United States. In controlled studies, efficacy has been detected in the majority (50 to 70 percent) of patients. The only prominent side effect is sedation occurring in up to 20 percent of adult patients. A patients acceptance and compliance with treatment with a drug such as ketotifen is dependent on psychologic, environmental and social factors, as well as on characteristics of the drug regimen. Drug-related characteristics comprise efficacy of the drug, adverse effects, frequent-dose regimens, and the physical feature of the drug itself. A slow-release oral formulation of ketotifen (Zaditen SRO) has been developed to improve patients’ overall acceptance and compliance by reducing the frequency of drug administration from twice to once per day. Additionally, it is anticipated that the incidence and severity of sedation may be reduced by eliminating fluctuations (peaks in blood levels) and by administering the drug before bedtime.
The present trial was designed to investigate the efficacy and tolerability of orally administered slow-release tablets containing 2 mg of ketotifen compared with placebo, in the treatment of mild extrinsic bronchial asthma.
Materials and Methods
Selection of Ihtients
Patients had to meet the following criteria for inclusion in the study: (1) age 6 to 40 years (children, 6 to 12 years; adolescents, 13 to 18 years; and adults, 19 to 40 years); (2) perennial symptoms of mild extrinsic bronchial asthma; (3) two to eight asthmatic attacks per month; and (4) unchanged antiasthmatic therapy over four weeks (run-in period). Extrinsic bronchial asthma had to be documented clinically and had to be confirmed by positive skin tests and a pulmonary function test (more than 20 percent reversibility of FEV, after 300 μg of albuterol [salbutamol]). Patients receiving desensitization within the last 12 weeks and patients with a history of corticosteroid treatment were excluded. Antihistaminic and prophylactic drugs (eg, cromolyn sodium [disodium cromolglycate]) were not allowed. Bronchodilators (ie, (3-sympathomimetics or theophylline) were permitted during the first eight weeks when necessary (for control of symptoms). An attempt was made to reduce the use of these drugs between weeks 9 and 12.