Excedrin Migraine Full Migraine Indication Approved By FDA

Bristol-Myers Squibb's Excedrin Migraine indication for full migraine syndrome was approved by FDA Oct. 7. The new labeling simply bears the indication "Treats migraine."

Current labeling includes the indication, "For the temporary relief of mild to moderate pain associated with migraine headache." Although shorter, the new claim encompasses the complete range of symptoms associated with migraine, such as severe pain, nausea, sensitivity to light or sound and difficulty performing usual functions.

The relabeled product will be on store shelves in the first quarter. The new label also is reformatted to bring the product into compliance with the new OTC labeling standards.

However, the substance of the new label is essentially the same as the old. The package contains the same warnings and directions as before.

Bristol-Myers noted it is still reviewing marketing plans for the product in light of the new indication.

"This approval confirms that the nonprescription medication Excedrin Migraine safely and effectively treats the same symptoms as leading prescription migraine drugs," BMS said.

In support of its application for the expanded indication, the company submitted to FDA "an expanded review" of results from three double-blind, randomized, placebo-controlled clinical trials of 1,250 migraine patients.

"The migraine headache pain relief program... demonstrates compelling and statistically significant evidence that the Excedrin Migraine formulation is effective in the treatment of the headache pain of migraine," the firm said.

The 1,250 patients with moderate to severe migraine pain were recruited through two complementary techniques - population and office practice - to ensure a broad sample of the migraine community, independent of physician consulting status.

The subjects were evaluated by one of 19 participating centers across the country. The most severe segment, including those with migraines that caused vomiting at least 20% of the time or those so incapacitated they required bed rest, were excluded.

"Study design and endpoints were all selected based on those used in [trials supporting] recently approved migraine medications and International Headache Society (IHS) guidelines for migraine trials," Bristol-Myers noted.

The subjects were randomly administered a single dose of Excedrin or placebo for migraine. After two hours elapsed, 59% of the patients on Excedrin who had experienced moderate or severe pain before taking the drug reported the pain had diminished to "mild" or "none." After six hours, more than three quarters (79%) of the Excedrin-treated subjects had mild to no pain.

Of the patients on placebo, 33% reported their pain had decreased after two hours. Just over half (52%) of those taking placebo experienced mild or no pain after six hours.

"The Excedrin Migraine formulation has an excellent OTC safety profile as demonstrated by clinical trial safety experience in multiple pain models, including tension-type headaches, and 19 years of previous marketing experience with more than 30 bil. tablets sold," Bristol-Myers said.

"No clinically significant safety concerns were identified in the clinical program," the firm added.

The company submitted its supplemental NDA for the indication for the tablet, caplet and geltab product Dec. 18, 1998. Follow-up submissions were made in May, June, July and September.

The user fee goal of 10 months for the supplemental NDA is Oct. 18, FDA notes in the approval letter. The agency adds that it has waived the pediatric study requirement for this application.

Excedrin Migraine was approved for migraine pain treatment in January 1998 (¹ (Also see "Bristol-Myers Squibb's Excedrin gains first approval for OTC migraine indication." - Pink Sheet, 19 Jan, 1998.)). The product is the same formula as Excedrin Extra Strength - 250 mg acetaminophen, 250 mg aspirin and 65 mg caffeine - but has different labeling focused on migraine.

Excedrin Migraine's marketing exclusivity is due to expire Jan. 14, 2001.