Crofelemer (Monograph)

Brand name: Mytesi
Drug class: Antidiarrhea Agents
Chemical name: Oligomeric proanthocyanidin from the latex of Croton lechleri
CAS number: 148465-45-6

Medically reviewed by Drugs.com on Apr 15, 2024. Written by ASHP.

Introduction

Antisecretory antidiarrhea agent; oligomeric proanthocyanidin mixture derived from red latex of Croton lechleri tree.^{1 2 3 4}

Uses for Crofelemer

Diarrhea

Symptomatic relief of noninfectious diarrhea in adults with HIV infection or acquired immunodeficiency syndrome (AIDS) receiving antiretroviral therapy.¹

Not indicated for treatment of infectious diarrhea.¹ (See Patients with Infectious Diarrhea under Cautions.)

Crofelemer Dosage and Administration

Administration

Oral Administration

Administer orally twice daily without regard to meals.¹ (See Absorption under Pharmacokinetics.)

Swallow delayed-release tablets whole; do not crush or chew tablets.¹

Dosage

Adults

Diarrhea

Noninfectious Diarrhea in HIV-infected Patients

Oral

125 mg twice daily.¹

Dosage adjustment not recommended based on CD4⁺ T-cell count or HIV viral load.¹ (See CD4⁺ T-cell Count and HIV Viral Load under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations;¹ dosage adjustments probably not necessary² since systemic absorption is minimal.^{1 10 11}

Renal Impairment

No specific dosage recommendations;¹ dosage adjustments probably not necessary² since systemic absorption is minimal.^{1 10}

Geriatric Patients

No specific dosage recommendations at this time;¹ dosage adjustments probably not necessary¹¹ since systemic absorption is minimal.^{1 10}

Cautions for Crofelemer

Contraindications

• Manufacturer states none known.¹

Warnings/Precautions

Patients with Infectious Diarrhea

Not indicated for treatment of infectious diarrhea.¹

Rule out infectious etiologies of diarrhea prior to initiating crofelemer.¹

If infectious etiologies not considered and therapy initiated based on presumptive diagnosis of noninfectious diarrhea, those with infectious etiologies may not receive appropriate treatment and their condition may worsen.¹

CD4+ T-cell Count and HIV Viral Load

Safety profile in HIV-infected patients with baseline CD4⁺ T-cell counts <404 cells/mm³ is similar to that in those with CD4⁺ T-cell counts ≥404 cells/mm³.¹

Safety profile in HIV-infected patients with baseline HIV viral loads ≥400 copies/mL is similar to that in those with HIV viral loads <400 copies/mL.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.¹

Common Adverse Effects

Upper respiratory tract infection, bronchitis, cough, flatulence, increased bilirubin concentrations.¹

Drug Interactions

Based on in vitro studies, potentially could inhibit CYP3A at concentrations expected in the gut.¹ Inhibition of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 in the liver unlikely since systemic absorption is minimal following oral administration.^{1 11} Does not induce CYP1A2, 2B6, or 3A.¹¹

Based on in vitro studies, potentially could inhibit multidrug resistance protein (MRP) 2 and organic anion transport protein (OATP) 1A2 at concentrations expected in the gut.¹

Specific Drugs

Crofelemer Pharmacokinetics

Absorption

Bioavailability

Acts locally in GI tract.¹⁰

Minimal systemic absorption following oral administration in healthy or HIV-infected individuals.^{1 10 11}

AUC and peak plasma concentration not established because plasma concentrations generally undetectable following oral administration.^{1 6 7 11}

Food

Administration with a high-fat meal in healthy individuals did not increase systemic exposure.¹

Distribution

Distribution not determined.¹

Extent

Not known whether distributed into human milk.¹

Elimination

Metabolism

Metabolites not identified in healthy or HIV-infected individuals.¹

Elimination Route

Not identified in humans.¹

Half-life

Not established because plasma concentrations generally undetectable following oral administration.^{1 6 7 11}

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C).¹

Actions

• A botanical drug product;¹ derived from red latex of Croton lechleri Müll. Arg, a tree found in western Amazonian region of South America.^{1 2 3 4 5} Botanical raw material from the tree has been called dragon’s blood (sangre de drago) or tree’s blood (sangre de grado).^{2 5}

• Oligomeric proanthocyanidin mixture consisting principally of catechin, epicatechin, gallocatechin, and epigallocatechin monomer units linked in a random sequence.^{1 2 3}

• Exact mechanism of action in treatment of noninfectious diarrhea not fully elucidated;^{6 7 8} appears to inhibit both cyclic adenosine-monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel and calcium-activated chloride channel (CaCC) at luminal membrane of enterocytes.^{1 2 3 4 8}

• CFTR chloride channel and CaCC regulate chloride and fluid secretion by intestinal epithelial cells.^{1 6 7}

• Decreases chloride secretion and accompanying high volume water loss resulting in normalization of chloride and water flow in GI tract, decreased stool weight and frequency, and symptomatic relief of diarrhea.^{1 2 6 7 8}

• Diarrhea in HIV-infected patients can be categorized as infectious (e.g., caused by opportunistic pathogens) or noninfectious (e.g., related to antiretroviral therapy, HIV enteropathy);^{2 3 9} some noninfectious causes may involve secretory mechanisms.^{2 3 7 9}

Advice to Patients

• Advise patients that crofelemer may be administered without regard to meals.¹

• Advise patients that crofelemer delayed-release tablets should be swallowed whole and not crushed or chewed.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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