Crofelemer, a novel agent for treatment of secretory diarrhea

Ann Pharmacother. 2010 May;44(5):878-84. doi: 10.1345/aph.1M658. Epub 2010 Apr 13.


Objective: To review the chemistry, pharmacology, pharmacokinetics, efficacy, and safety of crofelemer.

Data sources: A literature search using the terms SP-303, Provir, and crofelemer was performed with PubMed (up to April 2010), Google Scholar, and selected Ovid bibliography searches. Additional references from the bibliographies of articles included in the search, as well as company and Food and Drug Administration Web sites, were also assessed.

Data extraction: English-language in vitro and clinical studies associated with the safety and efficacy of crofelemer were included.

Data synthesis: Crofelemer is a first-in-class agent that may be useful for different types of secretory diarrhea, since it prevents chloride and fluid secretion into the bowel by directly inhibiting 2 distinct intestinal chloride channels. Crofelemer significantly brought about faster symptom resolution in patients with traveler's diarrhea, along with lower rates of treatment failure compared to placebo-treated patients. In a post hoc analysis, crofelemer compared to placebo also appears to have reduced abnormal stool weight and frequency in patients with AIDS-associated diarrhea. In a third trial, crofelemer did not offer a significant benefit in improving stool consistency after 12 weeks of treatment in patients with diarrhea-predominant irritable bowel syndrome. However, a significant increase in pain-free days was noted in female patients. Preliminary studies also show that crofelemer may reduce watery stool output in patients with infectious diarrhea such as cholera. Oral crofelemer seemed to be well tolerated in clinical trials, with adverse effect profiles comparable to those with placebo.

Conclusions: Crofelemer possesses a novel mechanism of action that shows promise in treating secretory diarrhea of several etiologies. However, results from further Phase 3 clinical trials are still needed in order to fully evaluate the efficacy and safety of this agent.

Publication types

  • Review

MeSH terms

  • Antidiarrheals / adverse effects
  • Antidiarrheals / pharmacology
  • Antidiarrheals / therapeutic use*
  • Chloride Channels / metabolism
  • Clinical Trials as Topic
  • Diarrhea / drug therapy*
  • Diarrhea / etiology
  • Diarrhea / metabolism
  • Humans
  • Intestinal Secretions / metabolism*
  • Proanthocyanidins / adverse effects
  • Proanthocyanidins / pharmacology
  • Proanthocyanidins / therapeutic use*
  • Treatment Outcome


  • Antidiarrheals
  • Chloride Channels
  • Proanthocyanidins
  • crofelemer