Joint Meeting of the Nonprescription Drugs Advisory Committee with the Gastrointestinal Drugs Advisory Committees

Food and Drug Administration

Center for Drug Evaluation and Research

Holiday Inn, Bethesda

NDA 21-229 Prilosec (20 mg for 14 days ) for OTC use

(NDA 21-229, omeprazole magnesium, Astra Zeneca LP/Procter and Gamble)

Currently, there are two classes of drugs, antacids and acid reducers (histamine-2 receptor antagonists), available in the over-the-counter (OTC) market to treat heartburn. Both, antacids and acid reducers, are indicated for the treatment of acute heartburn symptoms. The acid reducers have an additional claim for the prevention of meal induced heartburn symptoms if ingested at specified times prior to a meal. Omeprazole, a proton-pump inhibitor, is currently indicated for prescription use for the treatment of duodenal and gastric ulcer, symptomatic GERD, erosive esophagitis, and pathological hypersecretory conditions. Clinical efficacy studies with omeprazole have established that it is not effective in treating acute symptomatic heartburn and does not prevent episodic meal induced heartburn (when taken shortly before a meal). Studies have established that omeprazole is most effective in preventing heartburn when taken repetitively on a daily basis. The sponsor is seeking to market Prilosec 1 OTC for the 24-hour prevention of heartburn in the population of frequent heartburn sufferers (defined as suffering heartburn on two or more days per week). The sponsor has proposed a 14-day daily treatment course.

Frequent heartburn may also be the presentation for consumers with serious underlying conditions (e.g. GERD +/- erosive esophagitis). The current direct-to-consumer marketing for prescription Prilosec is directed toward consumers with heartburn symptoms occurring as frequently as two or more days a week and encourages them to contact their physician. For Prilosec 1, the Drug Facts label states that it should be used for frequent heartburn and only for those who suffer heartburn two or more days per week. Thus, the same symptomatic heartburn population will be directed to either use Prilosec 1 or prescription Prilosec.

1. Population

If Prilosec is available OTC, the sponsor acknowledges that some consumers with GERD +/- erosive esophagitis will choose to use Prilosec 1. Is it acceptable that some patients with GERD +/- erosive esophagitis self-treat with OTC medication? Please explain under what circumstances this is acceptable or not acceptable.

 

2. Self Selection

• having < 2 heartburn episodes per week;
• with relative contraindications for use that require a discussion with a physician before use;
• desiring acute symptomatic relief; and

• episodically (not on a daily basis).

1. Actual Use

In the actual use study, the sponsor provides information on the behavior of consumers who have a reoccurrence of heartburn symptoms after completing the 14-day course of therapy. Did consumers who had a reoccurrence of heartburn symptoms respond appropriately? When answering this question comment on the likelihood that consumers will seek advice from a health care professional (HCP) or the likelihood of the consumer using the product again without the advice of a HCP. Describe any other data in the submission that support your answer.

 

2. Duration and Repeat Use

• Given that the treatment for GERD with erosive esophagitis is a minimum of 28 days, is the proposed 14-day duration of therapy acceptable for this population? Or, should the treatment duration be longer than 14 days to insure that consumers with GERD are adequately treated?

1. Approvability

• Should the labeling specify a time period after which another course of Prilosec 1 can be taken without the need to speak to a physician (e.g. the consumer develops frequent heartburn 6 months after the initial course of Prilosec 1)?

• If yes, is there a limit on the number of courses a consumer should take over a period of time?

• Are their any additional labeling or marketing suggestions that might assure the appropriate use of Prilosec 1 (e.g. should the label state what types of heartburn Prilosec is not effective in treating)? Given that Prilosec 1 and prescription Prilosec will be marketed to the same symptomatic population, please explain how a consumer should determine the appropriate course of action when they experience frequent heartburn (i.e. purchase the OTC product or contact a physician).

• Should the agency require any phase IV commitments to assess the appropriate use of Prilosec 1?

• What additional information needs to be provided by the sponsor to support the approval of Prilosec 1?