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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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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Non-infectious diarrhea •••••••••••• ••••• - 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
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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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Treatment Herpes Simplex / Human Immunodeficiency Virus (HIV) Infections 2 somestatus stop reason just information to hide 4 Completed Treatment Acquired Immune Deficiency Syndrome (AIDS) / Healthy Volunteers (HV) / HIV Diarrhea / Human Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) 1 somestatus stop reason just information to hide 4 Recruiting Treatment Chronic Diarrhea of Unknown Origin 1 somestatus stop reason just information to hide 4 Terminated Treatment Diarrhea 1 somestatus stop reason just information to hide 3 Completed Prevention Adult Solid Tumor / Cancer Therapy-Related Diarrhea / Chemotherapy-related Diarrhea / Prophylaxis of Diarrhea / Symptomatic Relief of Diarrhea / Targeted Therapy-related Diarrhea 1 somestatus stop reason just information to hide
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
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Calcium-activated chloride channel (CaCC) (PubMed:20056604, PubMed:22178883, PubMed:22946059, PubMed:32487539). Plays a role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development. Required for CFTR activation by enhancing endoplasmic reticulum Ca(2+) store release and is also required for CFTR membrane expression (PubMed:28963502). Required for basal and ATP-dependent mucus secretion in airways and intestine, probably by controlling exocytosis of mucus-filled granules by providing Ca(2+) to an apical signaling compartment (By similarity). Contributes to airway mucus expression induced by interleukins IL3 and IL8 and by the asthma-associated protein CLCA1 and is required for expression of mucin MUC5AC (PubMed:33026825). However, was shown in another study not to be required for MUC5AC expression (PubMed:31732694). Plays a role in the propagation of Ca(2+) waves in Kolliker's organ in the cochlea and contributes to the refinement of auditory brainstem circuitries prior to hearing onset (By similarity). In vomeronasal sensory neurons, modulates spontaneous firing patterns in the absence of stimuli as well as the firing pattern of pheromone-evoked activity (By similarity). Responsible for calcium-activated chloride channel activity in type I taste cells of the vallate papillae (By similarity). Acts as a heat sensor in nociceptive neurons (By similarity). In dorsal root ganglion neurons, plays a role in mediating non-histaminergic Mas-related G-protein coupled receptor (MRGPR)-dependent itching, acting as a downstream effector of MRGPRs (By similarity). In the developing brain, required for the Ca(2+)-dependent process extension of radial glial cells (By similarity)
- Specific Function
- calcium-activated cation channel activity
- 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
- Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:12529365, PubMed:12588899, PubMed:12727866, PubMed:15010471, PubMed:17036051, PubMed:1712898, PubMed:17182731, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:26846474, PubMed:28087700, PubMed:8910473, PubMed:9804160). Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (PubMed:11524016, PubMed:15284228, PubMed:26627831, PubMed:8910473). The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). In vitro, mediates ATP-dependent glutathione flux (PubMed:12727866). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22121115, PubMed:22178883, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17182731, PubMed:17434346, PubMed:27941075). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731, PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810)
- Specific Function
- ABC-type transporter activity
- 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