Prilosec GERD Treatment Behavior Shown In Actual Use Studies - FDA

Consumers using AstraZeneca/Procter & Gamble's Prilosec 1 (omeprazole 10 mg) to prevent heartburn are likely to take the drug for longer than the 10-day limit set in proposed OTC labeling, according to agency reviewers.

FDA Division of OTC Drug Products Medical Officer Ling Chin, MD, told joint FDA advisory committees that among the actual use study participants identifying themselves as taking Prilosec 1 to prevent heartburn, 51% used the drug more than 25 days in a row.

Conversely, 80% of those who said they used the proton pump inhibitor to relieve heartburn dosed only one to two consecutive days.

The agency's Nonprescription and Gastrointestinal Drugs Advisory Committees voted Oct. 20 against the PPI for episodic heartburn relief, but left open the possibility of an OTC indication for gastroesophageal reflux disorder (GERD), also referred to as chronic heartburn (¹ (Also see "Prilosec GERD Indication OTC Appropriateness Debated At NDAC Meeting" - Pink Sheet, 23 Oct, 2000.)).

Four actual use studies enrolled 2,345 participants who received either 20 mg or 10 mg Prilosec with indications either to prevent symptoms for 24 hours or to relieve heartburn. Labeling instructed participants to use only one tablet per dose, to take only one pill per day and to use the drug for no longer than 10 consecutive days.

Chin reported full compliance with these directions ranged from 58%-75% in three of the studies, which she described as "not impressive." The FDAer also noted the 10-day limit was the most commonly ignored direction, with noncompliance ranging from 17%-22%.

Study recruitment also was slanted toward frequent heartburn sufferers, Chin noted. Those who reported experiencing heartburn roughly three or more times a week made up 19%-25% of the participants, while 34%-45% said they got heartburn at least twice a week and 36%-40% said once a week or less.

Chin further suggested the compliance results may have been biased because 18%-25% of participants did not properly fill in their journals. Such subjects may have been more noncompliant, she postulated.

Labeling the product with a 24-hour prevention claim encouraged people to use Prilosec to treat "more frequent and longstanding heartburn, which is GERD," she concluded, adding, "the proposed label does not provide adequate information of such use."

In their original proposal, AstraZeneca and P&G proposed a 20 mg dose and a dual relief/24-hour prevention claim similar to the indication on the drugs provided to study participants.

By the time of the meeting, however, the sponsors had altered their petition by halving the dose and requesting approval of a claim to treat frequent heartburn.

Panel member Marvin Schuster, MD, Johns Hopkins Bayview Medical Center, noted "the group now that is being proposed...essentially is [the] prevention-only group...[which] is the group which was most noncompliant, which most misunderstood the directions."

Bernard Schachtel, MD, Yale University School of Medicine, presented data for the sponsors intended to mitigate the contention that prevention-only users acted in ignorance or simply disregarded labeling directions.

In study 003, 50 prevention users who took the drug for over 10 consecutive days were polled to learn why. "Approximately 70%...had either been taking Prilosec on prescription, had [such use] recommended that way by their doctor or...during the study consulted with their physician," Schachtel explained.

In study 022, 22% of participants failed to abide by the 10-day limit. Of those, roughly 43% did so because of recent experience with an Rx PPI or H2 antagonist, while the rest did not comply because of discussions with a doctor either during or prior to the study about heartburn or Prilosec specifically, Schachtel said.

The sponsor rep also pointed out that 28% of the study populations identified themselves as "prevention only" users, while 56% said they used the drug for relief alone and the remainder reported no predominant use.

High levels of compliance were recorded with regard to taking one tablet at a time (91%-98%) and days taking only a single dose (96%-99%), Schachtel added.