Identification
- Summary
Crofelemer is an antidiarrheal agent used for the symptomatic relief of drug-induced non-infectious diarrhea in adult patients with HIV/AIDS receiving antiretroviral therapy.
- Brand Names
- Mytesi
- Generic Name
- Crofelemer
- DrugBank Accession Number
- DB04941
- Background
Crofelemer, previously known as the investigational drug SP-303, is a novel proanthocyanidin purified from the bark latex of the Amazonian Croton tree Croton lechleri. It is marketed under the brand name Fulyzaq and indicated for the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.
- Type
- Small Molecule
- Groups
- Approved
- Synonyms
- Crofelemer
- External IDs
- NP-303
- SP 303
- SP-303
- TRN-002
Pharmacology
- Indication
For the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.
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- Contraindications & Blackbox Warnings
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Crofelemer is an inhibitor of secretory diarrhea via inhibition of the CFTR chloride transporter. Crofelemer is not an antimicrobial, and therefore does not drive the emergence of resistance; it does not inhibit motility, and therefore does not cause constipation or rebound diarrhea; and it is not systemically absorbed, reducing the potential for adverse drug interactions and toxicity.
- Mechanism of action
Crofelemer is an inhibitor of the cystic fibrosis transmembrane regulator chloride channel (CFTR), as evidenced by its activity on cell cultures, single cell patch clamps, single CFTR channels, and elaboration of mouse intestinal fluid secretion. Crofelemer also inhibits calcium activated chloride channels (CaCC), which in combination with CFTR, are expressed on the luminal side of intestinal cells. Crofelemer inhibition of both of these channels prevents water loss from diarrhea by inhibiting chloride secretion.
Target Actions Organism AAnoctamin-1 antagonistHumans ACystic fibrosis transmembrane conductance regulator antagonistHumans - Absorption
The absorption of crofelemer is minimal and crofelemer concentrations in plasma are below the level of quantitation (50 ng/mL).
- Volume of distribution
Since crofelemer is not significantly absorbed, volume of distribution was not quantified.
- Protein binding
Since crofelemer is not significantly absorbed, protein binding was not quantified.
- Metabolism
Since crofelemer is not significantly absorbed, no metabolites have been identified.
- Route of elimination
Since crofelemer is not significantly absorbed, the route of elimination has not been identified.
- Half-life
Since crofelemer is not significantly absorbed, the half life was not determined.
- Clearance
Since crofelemer is not significantly absorbed, clearance was not determined.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most common adverse effects are cough, flatulence, upper respiratory tract infection, bronchitis, and increased bilirubin.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Take with or without food.
Products
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- Provir / Virend
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Fulyzaq Tablet, coated 125 mg/1 Oral Salix Pharmaceuticals 2012-12-31 2017-12-31 US 
Mytesi Tablet, coated 125 mg/1 Oral Napo Pharmaceuticals, Inc. 2016-08-01 Not applicable US
Categories
- ATC Codes
- A07XA06 — Crofelemer
- Drug Categories
- Alimentary Tract and Metabolism
- Antidiarrheals
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Benzopyrans
- Biopolymers
- Chromans
- Chromones
- Compounds used in a research, industrial, or household setting
- Flavonoids
- Heterocyclic Compounds, Fused-Ring
- Macromolecular Substances
- Polymers
- Pyrans
- Tannins
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- PY79D6C8RX
- CAS number
- 148465-45-6
References
- General References
- Crutchley RD, Miller J, Garey KW: 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. [Article]
- External Links
- KEGG Drug
- D03605
- PubChem Substance
- 347909853
- 1364449
- ChEMBL
- CHEMBL2108184
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Crofelemer
- FDA label
- Download (357 KB)
- MSDS
- Download (566 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Acquired Immune Deficiency Syndrome (AIDS) / Healthy Subjects (HS) / HIV Diarrhea / Human Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) 1 4 Recruiting Treatment Chronic Diarrhea of Unknown Origin 1 4 Recruiting Treatment Diarrhea 1 3 Completed Treatment Diarrhea With HIV / HIV Enteropathy 1 3 Completed Treatment Diarrhea / Human Immunodeficiency Virus (HIV) Infections 1 3 Completed Treatment HIV Associated Diarrhea 1 3 Recruiting Prevention Cancer Therapy-Related Diarrhea / Chemotherapy-related Diarrhea / Prophylaxis of Diarrhea / Solid Tumors, Adult / Symptomatic Relief of Diarrhea / Targeted Therapy-related Diarrhea 1 2 Completed Prevention Breast Cancer 1 2 Completed Treatment Colonic Diseases / Diarrhea / Gastrointestinal Diseases / Irritable Bowel Syndrome (IBS) 1 2 Completed Treatment Irritable Bowel Syndrome (IBS) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, coated Oral 125 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7341744 No 2008-03-11 2020-11-14 US US8962680 No 2015-02-24 2031-10-31 US US8574634 No 2013-11-05 2018-01-11 US US7323195 No 2008-01-29 2018-06-07 US US9585868 No 2017-03-07 2031-10-31 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
- Not Available
- Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Voltage-gated chloride channel activity
- Specific Function
- Calcium-activated chloride channel (CaCC) which plays a role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal...
- Gene Name
- ANO1
- Uniprot ID
- Q5XXA6
- Uniprot Name
- Anoctamin-1
- Molecular Weight
- 114077.215 Da
References
- Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Pdz domain binding
- Specific Function
- Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO...
- Gene Name
- CFTR
- Uniprot ID
- P13569
- Uniprot Name
- Cystic fibrosis transmembrane conductance regulator
- Molecular Weight
- 168139.895 Da
References
- Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. [Article]
Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51