FDA approves crofelemer

FDA’s recent approval of crofelemer (Fulyzaq, Salix Pharmaceuticals, under license from Napo Pharmaceuticals), 125 mg delayed-release tablets, the first anti-diarrheal drug for HIV/AIDS patients taking antiretroviral therapy (ART), is a significant step forward in addressing the unmet medical need of people with HIV/AIDS on ART who experience noninfectious diarrhea, which often can lead to reduced treatment compliance.

“HIV-associated diarrhea impacts many aspects of a patient’s care plan,” according to Patrick G. Clay, PharmD, FCCP, CCTI, consultant pharmacologist for FDA and professor of pharmacy practice at University of North Texas System College of Pharmacy, in Dallas.

“Of importance to hospital administration, managed care organizations and health facility personnel are finding ways to improve a patient’s quality of life, nutritional status, and normalizing bowel movements.” Dr Clay told Formulary. “Physicians, clinical pharmacists, nurses and dieticians would agree that normalization of bowel movements makes everyone’s responsibilities more easily accomplished.”

The safety and efficacy of crofelemer were established in a clinical trial of 374 HIV-positive patients on stable ART with a history of diarrhea lasting 1 month or longer. The median number of daily watery bowel movements was 2.5 per day.  Patients who had diarrhea caused by an infection or a gastrointestinal disease were excluded from participating in the trials. Patients were randomly assigned to take crofelemer or a placebo twice daily.

The trial was designed to measure clinical response, defined as the number of patients who had 2 or fewer watery bowel movements weekly. Results showed that 17.6% of patients taking crofelemer experienced clinical response compared with 8% taking placebo. In some patients, a persistent anti-diarrheal effect was seen for 20 weeks.

“While not specifically evaluated in the studies, gastrointestinal transit time is commonly reduced in persons with loose stools as compared to those with normal stools,” Dr Clay said. “By reducing watery bowel movements, the likelihood of normalizing absorption of concomitantly administered medications is enhanced.”

In environments where intravenous (IV) medications to their oral (PO) counterparts are a major focus for cost savings, normal bowel movements are clinically important to consider before that switch is recommended, according to Dr Clay.

“Not to be overlooked is the fact that many persons with HIV are first provided their diagnosis at the time of admission for an opportunistic infection; therefore, health systems represent the earliest time point at which anti-HIV medications are prescribed,” he said.

“Emergency room physicians, hospitalists, and physician-extenders, even those not recognized as HIV experts, can initiate crofelemer with the knowledge that it underwent extensive drug interaction testing and demonstrated an excellent safety profile as the only agent specifically studied and approved for use in noninfectious HIV-associated diarrhea-especially in those who have previously undergone numerous over-the-counter anti-diarrheal preparations,” said Dr Clay.

The price of crofelemer has not been determined; however, it could be speculated that by allowing persons to switch from IV to oral antibiotics by normalizing bowel movements would be a realized cost, according to Dr Clay.

Derived from the red sap of the Croton lechleri plant, crofelemer is the second botanical prescription drug approved by FDA. A botanical drug product is often a complex mixture derived from 1 or more plant materials with varying degrees of purification.