Bowel drug to go back on market
FDA allows restricted marketing only
In an unprecedented move, the Food and Drug Administration (FDA) announced that it would allow the restricted sale of a drug that had been pulled off the market because of severe side effects — including several patient deaths.
The indication for alosetron hydrochloride (Lotronex) has been narrowed to only women with severe, diarrhea-predominant irritable bowel syndrome (IBS) who have failed to respond to conventional IBS therapy. Less than 5% of IBS cases are considered severe, and even fewer of these cases are diarrhea-predominant IBS. The drug’s manufacturer, GlaxoSmithKline (GSK), is implementing a risk management program, which includes an enrollment program for physicians who want to prescribe the drug.
The FDA first approved alosetron HCl in February 2000. GSK voluntarily pulled the drug off the market nine months later after reports of serious complications of constipation and ischemic colitis.
IBS patients upset over alosetron HCl’s removal pleaded their case through letters, e-mail, telephone calls, and public testimony. GSK then resumed negotiations with the FDA about the drug, and submitted a Supplemental New Drug Application in December 2001. The FDA’s final June 7 decision follows an April 23 recommendation by the FDA’s Gastrointestinal Drugs Advisory Committee and the Drug Safety and Risk Management Subcommittee of the Advisory Committee for Pharmaceutical Science to restore access to alosetron HCl through a restricted distribution and use program.
Risk management program requires teamwork
GSK’s Lotronex Risk Management Program emphasizes the need for physicians, patients, and pharmacists to work together to maximize the benefit of alosetron HCl and minimize the risk, the FDA says. The program includes the following components:
• For safety reasons, alosetron HCl should be started at a dosage of 1 mg orally once a day for four weeks. If, after four weeks, the 1 mg once-a-day dosage is well-tolerated but does not adequately control IBS symptoms, then the dosage may be increased to 1 mg twice a day, the dose used in controlled clinical trials.
• GSK will establish a prescribing program to enroll physicians who plan to prescribe alosetron HCl. Enrollment will be based on physician self-attestation of qualifications and acceptance of certain responsibilities in prescribing the medication.
GSK will enroll physicians in the prescribing program who agree to educate patients on the risks and benefits of alosetron HCl treatment and to provide patients a copy of the FDA-approved Medication Guide.
• Patients will be asked to read and sign a Patient-Physician Agreement before receiving their initial prescription for alosetron HCl. The agreement attests that they are informed about risks and benefits of alosetron HCl and agree to follow directions that are elements of the plan.
Patients will be advised to discontinue use if they have not obtained adequate control of their IBS symptoms after four weeks of treatment with 1 mg twice a day. Patients also will be advised to contact a doctor immediately if they have any symptoms of side effects.
• Pharmacists will be asked to fill only prescriptions that display a prescribing program sticker affixed by an enrolled physician, and to give patients a copy of the FDA-approved Medication Guide every time they dispense the drug.
• Physicians enrolled in the program will agree to report serious adverse events to GSK.
GSK will conduct an ongoing assessment of the Risk Management Program, including a study of the prescribing and actual use of alosetron HCl.
Group advocates even tighter restrictions
While many IBS patients lauded the FDA’s decision, one consumer advocacy group condemned it. Public Citizen, based in Washington, DC, is concerned that the risk management program does not require verification of doctors’ qualifications or checks to ensure that patients have been informed of the drug’s risks. Tracking of adverse effects will not be mandatory, either. Finally, allowing the drug’s manufacturer to administer the program is a case of "the fox guarding the henhouse," says Larry Sasich, PharmD, MPH, a pharmacist and research analyst with Public Citizen’s Health Research Group.
Instead, the FDA should have limited alosetron HCl to research status, which requires tight controls on who receives a drug and documentation of the effectiveness and safety of a drug, he says. Under that status, the FDA should have limited the drug to women who had previously used it and had experienced no adverse effects.
Also, at a minimum, the risk management program should be restricted to registered gastroenterologists, he adds. There should be a patient registry, and the pharmacies that dispense the drug also should be registered with the FDA.
The consumer advocacy group worries that alosetron HCl’s reintroduction will harm more patients. "We are quite fearful for [them]," Sasich says.
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