Adams Mucinex Approval Spurs FDA Crackdown On Guaifenesin Products

Unapproved, single-ingredient guaifenesin extended-release Rx products should no longer be marketed because there is now an approved OTC version, according to FDA.

In light of the agency's July approval of Adams Labs' new drug application for OTC Mucinex , FDA said it will pursue enforcement actions if necessary against unapproved solid oral dosage forms of such guaifenesin products.

FDA noted the expectorant is not "medically necessary." In addition, immediate-release guaifenesin is widely available OTC, and the agency has no concerns that Adams Labs will not be able to meet the demand for the extended-release product, FDA said.

In 70 warning letters issued Oct. 11, FDA advises manufacturers, distributors, marketers and retailers of single-ingredient guaifenesin extended-release products that such Rx items are "new drugs and require an approved application for marketing." The letters encompass 42 different products, most of which are 600 mg and 1,200 mg guaifenesin tablets or caplets.

The warning letters note that although guaifenesin is a Category I ingredient under the expectorant drug products final monograph, "the OTC monograph system does not include provisions for extended-release dosage form drug products." Through rulemaking, FDA has "accorded new drug status" to extended-release dosage forms, the agency notes.

Prior to approval of any NDA for single-ingredient guaifenesin extended-release products, "FDA did not expend scarce enforcement resources to address such unapproved products," the letter states. However, the agency points to the July 12 OTC approval of Mucinex 600 mg guaifenesin extended-release tablets for use as an expectorant by individuals 12 and older.

Once the first marketing application is approved, FDA considers enforcement against similar, unapproved products to be a higher priority, in part, as an incentive for firms to file their own formal applications for approval, the agency said.

"We request that you reply within 15 days of your receipt of this letter stating what action you plan to take to bring this product into compliance with applicable requirements," the agency states. If appropriate corrective action is not taken, "FDA may initiate legal action," such as seizure or injunction.

Corrective action could include the filing of NDAs, ANDAs or 505(b)(2) "paper NDAs." However, the agency said it is not inclined to postpone enforcement while companies are putting together their applications, pointing to its longstanding policy against exercising enforcement discretion unless products are medically necessary and there is a risk of shortage if the product is removed from the market.

Adams said approval of Mucinex automatically triggered provisions of the Durham-Humphrey Amendment of 1951, under which a drug cannot be marketed simultaneously both Rx and OTC at the same strength and dosage and for the same indication.

Companies issued warning letters include Biovail Pharmaceuticals, UCB Pharma, Respa Pharmaceuticals and Ivax Labs. UCB said it is "fully exploring all options" and will be in communication with FDA later this month. Ivax said it is "confident" the company can address the issues with FDA.

Mucinex, which has almost reached full distribution, is being positioned "behind the counter" (¹ (Also see "Adams Labs Mucinex Marketing Strategy Targeting Healthcare Professionals" - Pink Sheet, 22 Jul, 2002.), p. 3). Adams said it is focusing initial marketing efforts on healthcare professionals, who write approximately 8 mil. prescriptions annually for single-ingredient, long-acting guaifenesin.

The company is awaiting FDA approval of its NDA for 1,200 mg guaifenesin extended-release tablets. In addition, Adams expects to file NDAs for OTC extended-released guaifenesin with a decongestant, as well as guaifenesin with dextromethorphan.

Adams currently sells such long-acting guaifenesin combination products under its Aquatab Rx brand. The drugs, along with numerous other companies' Rx extended-release guaifenesin combination products, also are unapproved. Consequently, approval of NDAs submitted by Adams or other sponsors could lead FDA to eventually take similar enforcement action against such combination products.

Adams said special friability studies of Mucinex that FDA required be performed as a condition of approval have been completed with satisfactory results. In addition, the company is phasing in child-resistant packaging for all Mucinex products and will not be required to include a label statement indicating the drug is for "households without young children."