With Lotronex, a guide is part of the package
Some rare but serious risks outlined
Pharmacists have a new responsibility every time alosetron (Lotronex) is dispensed — They need to dispense some warnings, too.
The Food and Drug Administration recently developed a medication guide to help ensure that women using alosetron hydrochloride (Lotronex), a serotonin 5-HT3 antagonist for the treatment of diarrhea-predominant irritable bowel syndrome (IBS), will understand the medication’s rare but serious risks early enough to prevent harm.
Risks include complications from constipation and the possible development of ischemic colitis as a result of reduced blood flow to the intestines. (Visit www.fda.gov/medwatch/safety/2000/ safety00.htm#lotron for health care professional letters, revised product information, the medication guide, and an FDA press release.)
Alosetron is the first drug to have a medication guide with regulations that became effective in 1999. A medication guide contains FDA-approved information, written especially for patients, that pharmacists are required to distribute with products the FDA has determined pose a serious risk.
"Medication guides provide a new way for the FDA to deal with these risks," Barry Browne, PharmD, coordinator of drug information at Scott and White Hospital and Health Plan of Temple, TX, tells Drug Utilization Review. "The fact that there is more information available now than at the time of drug approval is very useful, and it’s important that that information be available both to health care providers and to patients. Patients need to be encouraged to contact their health care professionals if and when they experience adverse events. The medication guide just reinforces the concept of contacting someone if adverse events begin."
The alosetron medication guide contains instructions for patients who become constipated while taking alosetron to contact their physicians right away. Patients are further instructed to stop taking alosetron immediately and to contact their physicians if they become severely constipated, have worsening or bothersome constipation with increased abdominal discomfort, or notice signs of ischemic colitis.
Information for health care professionals also has been updated. The FDA says the benefits of alosetron in patients with diarrhea-predominant IBS outweigh the risks of the drug when used according to instructions in the medication guide.
The new safety information relates reports of constipation that, in a few cases, have resulted in serious sequelae, and infrequent reports of ischemic colitis occurring in association with the use of alosetron.
With each script, a note
In its "Dear Pharmacist" letter, alosetron manufacturer Glaxo Wellcome informs pharmacists that the FDA requires them to give patients a copy of the medication guide with each new and refilled prescription of alosetron. Previously, an "Information for Patients" sheet was provided as a tear-off section of the prescribing information. That has become the medication guide.
"The FDA’s requirement of a medication guide does not necessarily raise a red flag for alosetron, but it certainly gives P&T committees something else to consider when reviewing the drug for formulary inclusion," Browne says.
At the time of approval of alosetron in February 2000, the labeling included warnings of occurrences of ischemic colitis and dose-related occurrences of constipation that had been reported in clinical trials. Subsequently, Glaxo Wellcome has received post-marketing reports of a few cases of serious complications, including obstruction, perforation, impaction, toxic megacolon, and secondary ischemia in patients treated with alosetron. In some cases, those complications have required intestinal surgery, including colectomy. Since approval, a few additional cases of ischemic colitis also have been reported; those cases are comparable in frequency and severity to the ones reported prior to approval.
The medication guide enables consumers as well as health care professionals to manage the risks inherent in most drug treatments more effectively. "I view it as another step in counseling patients," Browne says.
Guide to alosetron
The alosetron medication guide, which will be attached to every bottle of the drug, provides patients with these instructions:
- Before starting alosetron, the patient should discuss with her physician the severity of her IBS symptoms, along with the possible benefits and side effects of alosetron, to decide if the drug is right for her.
- Alosetron is only for women with diarrhea-predominant IBS; women with constipation as the primary IBS symptom should not use
alosetron.
- Because alosetron does not cure IBS or work for everyone, women are advised to discontinue the drug and tell their physicians if their IBS symptoms do not improve within four weeks of starting the drug.
- Alosetron has not been shown to be effective in men.
The updated labeling for health care professionals states that alosetron is now contraindicated in women with:
- a history of intestinal obstruction, stricture, toxic megacolon, gastrointestinal perforation, and /or adhesions;
- a history of ischemic colitis;
- active diverticulitis;
- current Crohn’s disease or ulcerative colitis, or a history of same.
Between the FDA approval of alosetron on Feb. 9, 2000, and June 1, 2000, the FDA received seven reports of serious complications of constipation in patients using alosetron. Those complications resulted in six hospitalizations, three of which required surgery. Although 25% to 30% of patients taking alosetron in clinical trials experienced constipation, the FDA received no reports of serious complications associated with those cases of constipation.
During that same time post-approval, the FDA received eight reports of ischemic colitis in alosetron patients, resulting in four hospitalizations and four endoscopic procedures, but no surgeries. Four patients also experienced colitis during clinical trials. All 12 patients with ischemic colitis recovered without serious consequences upon discontinuing alosetron.
"To detect certain rare adverse events associated with drugs, the drug must be given to approximately 200,000 patients. Detection of this nature typically comes only once a drug has reached the market," Browne says.
It requires not only the open market and numerous patient exposures, but also use by patients in the manner in which they actually take medications, which is not always exactly as directed by their pharmacists or physicians.
"We’ve come a long way in medicine and pharmacy since the 1920s and 1930s, when patients were handed a prescription they couldn’t read and were dictated instructions on the administration of their drugs," Browne says. "Today, it’s more of a contractual relationship between physician, patient, and pharmacist. Patients must take a more active role in their own care. The medication guide will help them put that responsibility into practice."
Pharmacists can help monitor the safety of alosetron by reporting adverse reactions to Glaxo Wellcome at (888) 825-5249, the FDA MedWatch program by telephone at (800) 332-1088, by fax at (800) 332-0178, or on the Web at www.fda.gov/medwatch.
source
- Barry Browne, PharmD, Coordinator of Drug Information, Scott and White Hospital and Health Plan, College of Medicine, Texas A&M University Health Science Center, 2401 S. 31st St., Temple, TX 76508. Telephone: (254) 724-5287.
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