Rx CARE

FDA approves restricted marketing of alosetron

Prompted by a strong patient outcry, the Food & Drug Administration recently took the unprecedented action of reapproving for marketing a drug that had been withdrawn. Patients with irritable bowel syndrome (IBS), claiming that alosetron (Lotronex, GlaxoSmithKline) was the only therapy that provided relief, had relentlessly lobbied the FDA and Glaxo following the voluntary withdrawal of alosetron by Glaxo in November 2000.

As a result, the FDA announced last month that it had approved a supplemental New Drug Application for alosetron. The drug is approved for the treatment of women with severe diarrhea-predominant irritable bowel syndrome who have failed to respond to conventional IBS therapy. Alosetron will become available again, pos-sibly within the next six months, through a restricted marketing program.

Alosetron was originally approved for marketing by the FDA in February 2000, and it was heralded as the first new treatment for irritable bowel syndrome in decades. It was withdrawn from the market nine months later amid reports of ischemic colitis and complications of constipation that, according to the FDA Web site, hospitalized 137 persons, required 45 patients to undergo major surgery, and resulted in four deaths. The FDA stipulated that alosetron be returned to the market with restrictions, because of the serious and unpredictable nature of these adverse events.

The components of the alosetron risk management program include:

• Labeling changes that present new safety information, including a black box warning

• Physicians' self-attestation of qualifications to manage IBS, prescribe alosetron, and manage the drug's adverse effects, and their agreement to educate patients and report serious adverse events to Glaxo and the FDA

• Modifications to the medication guide that present new safety information for patients taking alosetron

• A patient agreement document to verify that the patient has read and understands the medication guide, agrees to alosetron therapy, agrees not to take alosetron if constipated, and agrees to discontinue therapy and contact their physician if alo-setron does not provide relief from IBS symptoms after four weeks.

Physicians who attest that their patients qualify to enroll in the alo-setron prescribing program will send the agreement to Glaxo and place a qualification sticker on all prescriptions for alosetron. To participate in the program, physicians must agree to provide patients with a medication guide at the time the first prescription is written. Pharmacists will also provide patients with a copy of the medication guide each time a prescription is refilled.

According to Joel Zive, R.Ph., manager, Zive Pharmacy and Surgical Inc., Bronx, N.Y., the alosetron risk management program provides pharmacists with the opportunity to play a valuable role in healthcare delivery. "I think that having pharmacists counsel patients about this drug only adds to our value in the delivery of medication. Pharmacists catch errors—either an oversight by the provider or actual pharmacy errors—when doing patient counseling," he said.

Zive agrees with the decision to reintroduce alosetron to the market. "This drug is for a specific patient population, and no other drug provides this kind of patient relief," he said. "Patients should not be excluded from using it because it was misused or certain criteria were not taken into account when it initially became available. This is where pharmacists can be very valuable. They can ensure the accuracy of the prescription, ensure that the patient is using the drug correctly, and check with the physician to verify the dose if the dose is particularly high."

The recommended starting dose for alosetron is 1 mg q.d. p.o. for four weeks. If this dosage is well tolerated after four weeks, the dosage can be increased to 1 mg b.i.d.

"I do not mean to sound clichéd, but pharmacists are the last stop before the patient gets the drug," Zive continued. "We are the guardians of drug therapy in this country. It would behoove GlaxoSmithKline to make sure that pharmacists are educated about this and include us in education and overall diagnosis."

Pharmacists can report an adverse event to the FDA by logging on to http://www.fda.gov/medwatch and clicking on "How to Report," or by calling (800) FDA-1088. They can also report adverse events to Glaxo at (888) 825-5249. The product labeling, physician agreement, medication guide, and patient-physician agreement are available at the FDA's alosetron Web page, http://www.fda.gov/cder/drug/infopage/lotronex/lotronex.htm , or by calling Glaxo at (888) 825-5249.

Charlotte LoBuono

Charlotte LoBuono. FDA approves restricted marketing of alosetron.

Drug Topics

2002;13:18.