Although safety risks for Lotronex (alosetron hydrochloride) and approved generics still exist, FDA has determined the risk evaluation and mitigation strategies (REMS) programs for these drugs are no longer necessary to ensure the benefits outweigh the risks of ischemic colitis and serious complications of constipation.

Prescribers can continue to prescribe, and patients can continue to take Lotronex and alosetron hydrochloride as they have been doing. Information about ischemic colitis, serious complications of constipation, and mitigation of these risks will remain in the prescribing information, including in the existing Boxed Warning, and the Medication Guide.

Below is specific information for prescribers and patients to manage the risks of ischemic colitis and serious complications of constipation associated with use of alosetron hydrochloride.

Health care professionals who prescribe Lotronex and alosetron hydrochloride should:

  • Know the risks associated with these drugs and select the appropriate patients to receive the drugs in accordance with the approved indication.
  • Counsel patients on the signs and symptoms of serious complications of constipation and ischemic colitis (e.g., rectal bleeding, bloody diarrhea, new or worsening abdominal pain).
  • Counsel patients to immediately stop using Lotronex/alosetron hydrochloride and contact their health care professional if they develop constipation or signs or symptoms of ischemic colitis.
  • Evaluate patients with signs or symptoms of ischemic colitis and immediately stop Lotronex/alosetron hydrochloride treatments in patients who develop signs or symptoms of ischemic colitis.

Patients who take Lotronex or alosetron hydrochloride should:

  • Not start taking Lotronex/alosetron hydrochloride if you are constipated.
  • Stop taking Lotronex/alosetron hydrochloride and call your health care professional immediately if you get:
    • constipated while taking Lotronex/alosetron hydrochloride
    • new or worse pain in your stomach area (abdomen)
    • Blood in your bowel movements
  • Not start taking Lotronex/alosetron hydrochloride again until your doctor tells you to do so.

Adverse events or quality problems experienced with Lotronex and approved generics should be reported to FDA's MedWatch Adverse Event Reporting program. FDA’s top priority is patient safety, and we will continue to monitor the safety of these drugs.

Background information on Lotronex and Alosetron REMS

Lotronex, originally approved in February 2000, was voluntarily withdrawn from the marketplace by the manufacturer in November 2000 due to serious postmarketing adverse events including at least 49 cases of ischemic colitis and 21 cases of serious complications of constipation, some of which were fatal, or required surgery or blood transfusions. Lotronex was reintroduced to the market in June 2002 with a risk management program with restricted distribution. FDA identified Lotronex as a product deemed to have in effect an approved REMS following the passage of the Food and Drug Administration Amendments Act (FDAAA) of 2007.

In 2010, FDA approved a REMS for Lotronex that required prescriber training and enrollment and safe-use conditions that included a form that was signed by the patient acknowledging the risks. The Lotronex REMS also required that pharmacies could only dispense Lotronex if the prescriber affixed a REMS program sticker on a hard copy prescription, which was intended to indicate prescriber compliance with the requirements. The first generic for alosetron hydrochloride was approved in 2015 with a separate but comparable REMS that had the same goal, objectives, and elements as the Lotronex REMS. In 2016, FDA approved modifications to the Lotronex REMS and the Alosetron REMS programs to make prescriber training voluntary and to remove the prescription sticker requirement.

Evidence to support eliminating the Lotronex and Alosetron REMS

Elimination of the Lotronex and Alosetron REMS programs are supported by the following:

  • Since 2016, when the Lotronex REMS and Alosetron REMS were modified to make prescriber training programs voluntary and to remove the prescription sticker requirement, FDA has not identified any new data suggesting a change in the frequency or severity of ischemic colitis and serious complications of constipation. Reporting of these adverse events associated with alosetron to the FDA Adverse Event Reporting System (FAERS) has been stable since 2002 and an increase in severe outcomes has not been observed. Additionally, an analysis of new female users of alosetron hydrochloride in FDA’s Sentinel Distributed Database from 2016 to 2020 found the rate of ischemic colitis consistent with that listed in the Prescribing Information.
  • FDA did not observe increases in drug utilization trends since the approval of the generic version of alosetron hydrochloride. Overall, there has been an ongoing downward trend in the estimated total number of patients receiving prescriptions for all alosetron hydrochloride products. Due to the availability of approved therapeutic alternatives, we do not expect drug usage to increase with removal of the REMS.
  • REMS assessments have indicated that surveyed prescribers understand the risks, the indicated patient population, and the need to counsel patients despite an ongoing downward trend in the number of prescribers who complete the voluntary training program. Surveyed patients understand the actions to take if they experience the risks.

Source: FDA