Crofelemer

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Crofelemer
Clinical data
Trade namesMytesi
Other namesSP-303
AHFS/Drugs.comMonograph
MedlinePlusa613016
License data
Routes of
administration		By mouth (oral tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityLittle or no absorption from the gut
Identifiers
CAS Number
PubChem SID
DrugBank
ChemSpider
  • none
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula(C15O6,7H12)n
Molar mass860–9100 g·mol−1

Crofelemer (

infectious diarrhea, and diarrhea in patients with irritable bowel syndrome.[2] It is a purified oligomeric proanthocyanidin from "dragon's blood", the sap of the South American tree Croton lechleri.[3]

Crofelemer treats the symptoms of disease, but it is not used to treat infectious diarrhea (diarrhea caused by infection of the digestive system by a bacterium, virus or parasite). It was initially developed by Napo Pharmaceuticals, which is a wholly owned subsidiary of Jaguar Health, Inc. A Phase III clinical trial for diarrhea in HIV patients was completed in 2012, and the drug was approved by the US Food and Drug Administration (FDA) on 31 December 2012.[4][5][6]

Mechanism of action

The drug is taken orally and works by modulating

calcium signaling.[3]

Crofelemer is minimally, if at all, absorbed from the gut into the bloodstream, and is mostly excreted in the stools.[7]

Adverse effects and interactions

Crofelemer is well tolerated; and the only adverse effects found in clinical studies were mild gastrointestinal effects at the same level as under placebo.[7] The most common adverse reactions (≥ 3%) are: upper respiratory tract infection, bronchitis, cough, flatulence and increased bilirubin.[1]

Origin and chemistry

Croton lechleri bark with a few drops of dragon's blood

Crofelemer is an oligomeric proanthocyanidin mixture primarily composed of (+)–catechin, (–)–epicatechin, (+)–gallocatechin, and (–)–epigallocatechin monomer units linked in random sequence, as represented below. The average degree of polymerization for the oligomers ranges between 5 and 7.5, as determined by phloroglucinol degradation. The substance is a purified

kDa.[3]

History of Crude Plant Latex (Dragon's Blood) and Crofelemer

The crude plant latex of C. lechleri is traditionally used in South American medicine for the treatment of diarrhea, wounds, inflammations,

herpes simplex did not show any benefit.[11] In 1999, crofelemer was reported to improve the symptoms of cholera toxin induced diarrhea in mice.[12] Crofelemer demonstrated reduction of duration of diarrhea and frequency of watery stools in patients with traveler's diarrhea[13] and patients with HIV/AIDS.[14] Crofelemer has also shown benefit in adult patients with acute infectious diarrhea from E. coli and salmonella,[15] and in patients with moderate to severe watery diarrhea from vibrio cholerae. Crofelemer has also been shown to improve abdominal pain and discomfort in patients with diarrhea-predominate irritable bowel syndrome.[16][17]

SP-303 was eventually named crofelemer and patented by Napo Pharmaceuticals, which licensed it to Glenmark Pharmaceuticals in 2005, for exclusive development and marketing rights in 140 emerging markets including India,

anti-retroviral therapy".[2][6]

The drug substance is manufactured by Glenmark Pharmaceuticals, and is manufactured as 125 mg delayed-release tablets by Patheon Pharmaceuticals Inc. for Napo Pharmaceuticals.[citation needed]

References

  1. ^ a b "Mytesi Full Prescribing Information".
  2. ^ a b Drugs.com: Crofelemer Approval Status
  3. ^
    PMID 19808995
    .
  4. ^ a b H. Spreitzer (10 September 2012). "Neue Wirkstoffe – Crofelemer". Österreichische Apothekerzeitung (in German) (19/2012): 22.
  5. ^ Clinical trial number NCT00547898 for "Safety and Effectiveness of 3 Doses of Crofelemer Compared to Placebo in the Treatment of HIV Associated Diarrhea (ADVENT)" at ClinicalTrials.gov
  6. ^ a b "FDA approves first anti-diarrheal drug for HIV/AIDS patients". FDA. Archived from the original on 2 January 2013. Retrieved 31 December 2012.
  7. ^
    S2CID 5426870
    .
  8. PMID 14736360
    .
  9. S2CID 260251205
    .
  10. PMID 23195881
    .
  11. PMID 7710268
    .
  12. PMID 9886979
    .
  13. S2CID 20877791
    .
  14. S2CID 23436243
    .
  15. ^ Sharma, Akhilesh. "Crofelemer Improves Acute Infectious Diarrhea Symptoms". Publication of the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Diseases Society of America (IDSA) 46th Annual Meeting.
  16. S2CID 23602684
    .
  17. PMID 31800542
    .
  18. ^ "Glenmark gets an arbitration upshot on anti-diarrheal compound Crofelemer". BusinessLine.
  19. ^ "Napo Terminates Salix for Breach of Agreement for Failure to Commercially Develop Crofelemer" (Press release). BusinessWire. 10 November 2011.
  20. ^ "What's Next In Line For Salix?". RTTNews. 27 August 2012.

External links

  • "Crofelemer". Drug Information Portal. U.S. National Library of Medicine.
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