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Alosetron to Return to Market

Donna Young

A medication to treat irritable bowel syndrome (IBS) has become the first drug withdrawn from the market for safety reasons to receive FDA’s approval to return.

In early June, FDA approved a supplemental new drug application that permits restricted marketing of alosetron hydrochloride (Lotronex) by GlaxoSmithKline (GSK). The company withdrew the drug from the market in November 2000—nine months after initial approval—amid reports of serious cases of ischemic colitis and other complications that led to more than 100 hospitalizations and at least four patient deaths.

Joyce Korvick, FDA deputy director of gastrointestinal and coagulation drug products, said the agency will require GSK to implement a risk management plan that includes an educational program aimed at prescribers of alosetron. The product’s newly approved labeling includes a black-box warning advising that only physicians who have enrolled in the educational program should prescribe alosetron. This warning also requires patients to read and sign a patient–physician agreement form before receiving a prescription for alosetron.

The new labeling recommends an initial alosetron dosage of 1 mg once daily, rather than the previous 1 mg twice a day, FDA officials said. But, according to the drug’s new labeling, if the 1 mg once-daily dosage is well tolerated but does not adequately control IBS symptoms after four weeks, the patient may take 1 mg twice daily—the dosage established to be safe and efficacious in previous clinical studies of alosetron.

The prescriber education program is similar to the one used by F. Hoffmann-La Roche Ltd. for its acne-control medication isotretinoin, which pharmacists now dispense only after they receive a prescription that bears a special yellow sticker (see December 15, 2001, AJHP News). To obtain the alosetron stickers, copies of the FDA-approved medication guide, and patient–physician agreement forms, prescribers must submit a physician agreement form to GSK.

Eric Carter, GSK’s vice president of gastrointestinal clinical development and medical affairs, said his company is developing educational activities specifically for pharmacists.

Although Roche’s prescriber program for isotretinoin is voluntary, said Florence Houn, director of one of FDA’s offices of drug evaluation, the new one for alosetron is not. She said FDA has greater control over the alosetron program than the one for isotretinoin and can rapidly withdraw alosetron from the market if the newly approved requirements are not followed. In addition, Houn said, GSK must conduct postmarketing studies of the drug, and FDA must approve all promotional materials before their release.

FDA will evaluate how the drug is dispensed, said agency officials. But it will be up to state boards of pharmacy to enforce the requirement for pharmacies to fill only those alosetron prescriptions that bear the sticker. Carter said his company is "working out the details" of the prescribing process with each state’s board of pharmacy.

The drug cannot be prescribed over the Internet, fax, or telephone, FDA officials said.

FDA has narrowed the drug’s indication to women with severe diarrhea-predominant IBS, a condition that officials said affects 185,000 women in the United States.

"However, if a physician in consultation and discussion with the patient who is a male feels that it is appropriate in the practice of medicine to prescribe this drug for that patient with serious disease, that is a decision and choice that’s left up to the health care provider and the patient," FDA’s Korvick said.