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Executive Summary

Fisons' chromolyn sodium is "probably ideal" as a candidate for an OTC switch, University of Florida professor Leslie Hendeles told a May 9 conference on Rx-to-OTC switches in Rockville, Maryland. The ingredient would have three logical OTC indications, Hendeles maintained: (1) intermittent or seasonal asthma related to allergies; (2) exercise-induced asthma; and (3) chronic asthma. All OTC indications should be restricted to prophylactic use, Hendeles said. The active ingredient is currently marketed as a prescription drug in the U.S. in five formulations for prevention of asthma and allergies. The prescription inhaler carries a boldface warning against use for treatment of acute asthma attacks. A switch endorsement by Hendeles for chromolyn sodium is particularly noteworthy because the University of Florida researcher was one of a handful of key figures from the medical community who vigorously fought the switch of inhaled metaproteranol in 1982-1983. Hendeles also told the May 9 conference that he now favors consideration of oral beta agonists as switch candidates. The May 9 conference was sponsored by the Drug Information Association. In the prevention of allergic asthma, Hendeles maintained that chromolyn "is a very potent prophylactic agent in this situation and it has the ideal property that it is virtually free of toxicity -- with the exception of some coughing that might occur as a result of inhaling the powder." He noted that the coughing is "less of a problem with the new metered dose formulation," the Spinhaler capsule inhaler delivery system. The 17-year-old drug has "virtually no toxicity," Hendeles pointed out. FDA Office of Drug Evaluation I Director Robert Temple agreed with Hendeles on the potential for a chromolyn switch for two indications. It does not "seem unreasonable," Temple said, to consider chromolyn OTC "for someone who has regular exercise-induced asthma, and conceivably for some antigen-induced asthma." The drug evaluation director viewed the chronic use as more problematic. "What would be harder for me to swallow," Temple said, "would be its use in chronic asthma prophylactically." The FDAer also pointed to the "benign" qualities of the drug. Fisons already has begun to prepare the consumer market for at least one formulation of chromolyn sodium, the nasal solution (Nasalcrom) for allergic rhinitis. Fisons began testing consumer ads for that product with full page spreads in USA Today during the first week of May. The Nasalcrom ads contained a brief summary and mentioned the product directly by name ("The Pink Sheet," May 8, T&G-1). Hendeles specifically referred to the nasal solution and topical ocular solutions as dosage forms which might be suitable for switch. The British firm is well-positioned to move chromolyn to OTC status in the U.S. with the recent purchase of the Pennwalt drug business. As part of that purchase, Fisons acquired the Pharmacraft Division with its established allergy line of Allerest and Sinarest. FDA's Temple has final sign-off authority on NDAs reviewed by five divisions (including the group reviewing pulmonary drugs). He let the switch conference know that he will take a special interest in proposals to move asthma products from prescription status. "I have a personal experience I will tell you about," Temple candidly acknowledged. "My son developed asthma at about age three. He was put on the [oral] beta agonists. He was incapable of taking aerosol, and he couldn't tolerate theophylline." Temple noted that the use of the chromolyn sodium Spinhaler was overlooked as an option for almost a year and a half. Temple's experience with the prescription oral beta agonists makes him cautious about consideration of that class for future Rx-to-OTC switches. His apparent reluctance regarding that switch is tied to two reasons: the use of oral beta agonists may delay further appropriate asthma treatment; and the oral drugs may have the same potential for side effects as the aerosols. "Asthma can be a potentially fatal illness," if not properly treated, Temple noted. "It isn't clear to me," he said, "that moving the population towards oral beta agonists instead of aerosols is necessarily a great idea." He observed that he is "very skeptical about the idea that the oral agents can't be abused, the idea that no one ever over-medicates in the face of increasing symptoms . . . It is not necessary to take twice as much just take it twice as often." Noting the "violence" of the objections to the switch of aerosol beta agonists, Temple said "the danger that they might be used in the face of progressing asthma" seems to relate to the questions of the switch of the oral forms of the drugs. While his personal experience has been with the use of the beta agonists in children, Temple expressed concern about self-medication by the elderly with the drugs. "I would be worried about an older population." The switch discussion for the beta agonists is particularly relevant because one of the major products in that class, albuterol, is coming off patent in its tablet form this December. Several generic applications have already been approved in anticipation of that patent expiration. A switch to OTC is generally recognized as one response by brandname marketers to new prescription generic competition. Hendeles attempted to distinguish the oral beta agonists from the aerosol forms in his comments. In cases of severe asthma, the Florida researcher maintained, "patients are not likely to overuse [the oral dosage form]. They do not pop a tablet every five minutes . . . In my experience, I have never seen a patient . . . who was overusing an oral beta agonist, because it causes tremors and shaking and they don't overtake this medication." The Florida researcher debated with Temple the concern about overuse of the oral beta agonists. He maintained that the oral beta agonists OTC would be better than current oral self-medication alternatives for asthma. "If, in fact, that you take the position that oral beta agonists can be abused," Hendeles contended, "then you should take Primatene and Bronkaid tablets off the market." Temple answered: "That is probably what I would do given the choice." The FDAer added with a note of irony: "I guess I think that they are not so effective that they do much harm." Hendeles also urged the switch of hydroxyzine (two Pfizer brands, Atarax and Vistaril, and a number of generics) to OTC as an antihistamine. The product is a prescription agent as an anti-anxiolytic and as an anti-pruritic. Referring to data from studies done over a decade ago, Hendeles maintained that "hydroxyzine, which is perhaps thought of as a prescription antihistamine, really has the greatest degree of potency and a measurable degree of safety." He suggested that it "would make an excellent choice for OTC use." His studies compared it in terms of efficacy to diphenhydramine, chlorpheniramine and cyproheptadine (MS&D's prescription Periactrin). Hendeles noted that in the late 1970's when he wanted to study hydroxyzine for allergic rhinitis, Pfizer "was so uninterested that they did not even give us the medication free." Temple noted that one concern with the use of hydroxyzine as a self-medication is the possibility that its use can be associated with falls by the elderly.

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