THEOPHYLLINE-EPHEDRINE COMBOS LACK EVIDENCE OF EFFICACY, FDA

THEOPHYLLINE-EPHEDRINE COMBOS LACK EVIDENCE OF EFFICACY, FDA stated in a marketing revocation notice published in the Feb. 29 Federal Register. On the basis of the agency's review as part of the Drug Efficacy Study Implementation (DESI), "the Director concludes that there is a lack of substantial evidence that each ingredient, including theophylline and ephedrine, makes a contribution to the claimed effects of the combination drug products . . . and that the dosage of each component is such that the combinations are safe and effective for a significant patent population," the notice stated. FDA based its conclusion on the Nov. 4, 1982 findings of the Pulmonary-Allergy Drugs Advisory Cmte. and a review of the available data, including all submissions by manufacturers of products and the results of a study sponsored by the agency in 1981. FDA said that its review revealed a lack of adequate evidence that ephedrine has a beneficial additive effect with theophylline. The "significant risks of serious side effects" associated with ephedrine are therefore "particularly disturbing," the agency continued, adding that the fixed combinations "do not permit the proper titration of theophylline." FDA concluded that "it thus appears preferable to titrate theophylline to an effective dose rather than to introduce ephredine as a second agent in a fixed combination product." FDA identified 14 specific combination products affected by the notice, which the agency has divided into three groups and handled separately based upon varying strengths of theophylline and ephedrine and the presence of other ingredients. Pending the opportunity for hearing announced in the notice, all NDA approvals for the products will have been withdrawn. Group 1 are products containing relatively small doses of the combination drugs which include phenobarbital. Group 2 are other higher dose combination products. And Group 3 are theophylline-ephedrine combinations with hydroxyzine. THEOPHYLLINE/EPHEDRINE COMBO DESI WITHDRAWALS The following specific products, and identical other products, were identified by FDA as lacking substantial evidence of effectiveness under the DESI review process. FDA grouped the products according to the strength of the combination and the presence of other ingredients. Group 1 Amodrine Tablets (Searle) Phedorine Tablets (Cooper Labs) Asminyl Tablets (O'Neal, Jones & Feldman) Group 2 Amesec Enseals and Pulvules (Eli Lilly) Aminophylline and Amytal Pulvules (Eli Lilly) Dainite Tablets (Mallinckrodt) Dainite-KI Tablets (Mallinckrodt) Luftodil Tablets (Mallinckrodt) Quadrinal Tablets and Suspension (Knoll) Quibron Plus Capsules and Elixir (Mead Johnson) Group 3 Brofed Tablets (Cord Labs) Hydroxyzine Compound Syrup Barre-Natl.) Unnamed drug product (Lemon) Marax Tablets and Syrup (Roerig)