Reviews of crofelemer showed the drug's clinical utility in diarrhea associated with HIV, but clinical trials comparing it to other antidiarrheals are still needed.
HIV-infected patients have an increased risk of experiencing diarrhea for a number of reasons, including infection, malignancy, enteropathy, and side effects of antiretroviral therapy (ART), especially those with protease inhibitors. Approximately 40 percent of HIV patients report that diarrhea has negatively affected their social lives. For some patients, persistent diarrhea can lead to choosing nonadherence to medications and withdrawal from care, while for others, diarrhea prompts attempting multiple therapies to find treatments that don’t cause or exacerbate the problem.
Diarrhea associated with HIV is often secretory, involving excess chloride ion secretion followed by sodium and water transport into the intestinal lumen. Secretory diarrhea can create electrolyte, acid balance, renal, and hypovolemic complications that are serious and sometimes fatal.
Use of drugs and interventions proven to reduce garden-variety diarrhea have been partially successful. In December 2012, the US Food and Drug Administration (FDA) approved Fulyzaq (crofelemer), a natural compound isolated from the stem bark latex of the Croton lechleri tree found in South America’s western Amazon region. Oral crofelemer, the sole agent approved for this condition, is not absorbed systemically and can be administered with or without food. Unlike other antidiarrheals, crofelemer doesn’t affect peristalsis or create intestinal viscous liquid by causing stool to hold water. This limits potential bloating, constipation, and flatulence.
In July 2013, three leading journals published reviews of crofelemer: HIV AIDS, The Medical Letter on Drug and Therapeutics, and Drugs. Their interest underscores the magnitude of the problem and crofelemer’s potential clinical utility. Patients who take ART that includes ritonavir at higher-than-usual doses may be able to stay on their regimens longer while experiencing few gastrointestinal adverse effects. The pivotal study leading to crofelemer’s approval included a diverse ethnic population, which is a strength of the drug. Crofelemer may be an effective, safe alternative to other antidiarrheals, although head-to-head clinical trials comparing crofelemer to other antidiarrheals are still needed.
As with any new drug, crofelemer’s adverse effect profile will not be clear until the results of post-marketing surveillance are collected and analyzed.