Prilosec GERD Indication Suitability For OTC Use Debated By Advisory Cmte.

Gastroesophageal reflux disease is appropriate for OTC treatment, but AstraZeneca/Procter & Gamble's NDA to switch Prilosec OTC is not approvable, FDA's Nonprescription and Gastrointestinal Drugs Advisory Committees voted at a joint meeting Oct. 20.

The committee voted 7-6 with one abstention in favor of using OTC drugs for the treatment of GERD or chronic heartburn. The panel also decided 9-3 with one abstention that the proposed labeling for Prilosec 1 (omeprazole 10 mg) did not appropriately communicate the benefits and risks of long-term use.

The joint committees voted 11-2 and 10-2 with one abstention that the drug was not approvable for acute relief or episodic relief of heartburn, respectively.

AstraZeneca and P&G modified the proposed indication and dosage for the product after submitting the NDA, precluding the committee from reviewing the new material.

The new proposed indication is for "treatment of frequent heartburn" with directions for use for "prevention due to food/beverage" or "only on days heartburn is expected."

The indications originally in the NDA read "for relief of heartburn, acid indigestion and sour stomach" and "for prevention of heartburn, acid indigestion and sour stomach brought on by consuming food and beverages or associated with events such as stress, hectic lifestyle, lying down or exercise."

The NDA also called for a once-daily 20 mg dose, but the sponsors proposed a 10 mg dose at the meeting.

Regarding Prilosec 1's indication, P&G Medical Director Nora Zorich, MD/PhD, disputed the assertion the drug is only appropriate for GERD, saying that, like H2 antagonists, "it could be used whether you only had [occasional] heartburn" or "for treatment in those persons who had heartburn on a more frequent basis, or somebody who has...bouts of heartburn."

The modification of the indication's wording shifted discussion toward the OTC appropriateness of a GERD indication itself.

Several committee members expressed confusion over the difference between GERD and heartburn. Committee member Sidney Cohen, MD, Temple University, claimed "there is no difference. GERD...is manifested by heartburn, and heartburn is the cardinal symptom of GERD."

The agency does not "really take a view on" whether GERD should be an OTC condition, FDA Division of OTC Drugs Director Charles Ganley, MD, said.

Center for Drug Evaluation & Research Medical Officer Mark Avigan, MD, however, noted a lack of label instructions for long-term use of omeprazole, necessary to address the chronic nature of GERD.

FDA's review of the companies' data takes aim at the once-daily 24-hour prevention claim and 10-day continuous treatment limit that would be carried by the OTC drug, noting it "suggests that the target population for this product is not the episodic heartburn sufferer. Daily, all day 'prevention' of heartburn is the goal of treatment therapy for non-erosive GERD."

The review adds "the sponsor does not...explain how the proposed indication is differentiated medically or symptomatically from GERD or how the study population in the submission was differentiated from GERD."

"If no differentiation is possible, approval of this product as proposed...will define GERD as an OTC condition," the document continues.

"The next question is whether it is appropriate to label an OTC product for 'management' of heartburn when a currently required element, treatment, does not exist."

The proposed NDA label also does not inform users the first dose may be inefficacious and that the drug requires repeat dosing for full efficacy. Labeling omeprazole "for episodic heartburn without [this] information... would in fact be mislabeling," the review states.

"These data require review in the context of the current OTC label for other heartburn remedies, the proposed OTC label for [omeprazole] and discussion of any further changes by the agency on the role of acid-reducing agents in the OTC market," the review continues.

If the switch were approved with a GERD treatment claim, the CDER document recommends a 10 mg dose, while conceding that the "optimal dose may differ depending on the approved indication."