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Crofelemer: A Review of its Use in the Management of Non-Infectious Diarrhoea in Adult Patients with HIV/AIDS on Antiretroviral Therapy

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Abstract

Crofelemer (Fulyzaq™) is a botanical drug substance (oligomeric proanthocyanidin) extracted from the stem bark latex of the Croton lechleri tree. Crofelemer undergoes minimal systemic absorption following oral administration; it acts locally within the gastrointestinal (GI) tract by inhibiting the two principal chloride ion channels in the luminal membrane of enterocytes. Crofelemer is the first (and so far only) agent to be approved by the US FDA specifically for the symptomatic relief of non-infectious (i.e. secretory) diarrhoea in adult patients with HIV/AIDS on antiretroviral therapy (ART). This approval was based on findings from the ADVENT study, a large (n = 376 randomized patients), multicentre, phase III trial in which the recommended dosage of oral crofelemer (125 mg twice daily) significantly reduced secretory diarrhoea in HIV-positive individuals on ART compared with placebo, as assessed over a 4-week period. Crofelemer was generally well tolerated in ADVENT (which included a 5-month placebo-free extension phase) and a 48-week, open-label, phase III safety study; infections and GI disorders were the most frequently reported treatment-emergent adverse events (TEAEs) in patients receiving the drug. Of note, the overall incidence of TEAEs was similar in the crofelemer and placebo groups during the 4-week placebo-controlled phase of ADVENT. Treatment with crofelemer had no appreciable effect on immune parameters, such as HIV viral load and CD4+ cell counts.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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  1. Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand

    James E. Frampton

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  1. James E. Frampton
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Correspondence to James E. Frampton.

Additional information

The manuscript was reviewed by: M.Holodniy, Division of Infectious Diseases, Stanford University Medical Center, Stanford, CA, USA; B.Illek, Fischer-Illek Lung Biology and Pathology Department, Children’s Hospital Oakland Research Institute, Oakland, CA, USA.

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Frampton, J.E. Crofelemer: A Review of its Use in the Management of Non-Infectious Diarrhoea in Adult Patients with HIV/AIDS on Antiretroviral Therapy. Drugs 73, 1121–1129 (2013). https://doi.org/10.1007/s40265-013-0083-6

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