Crofelemer is a botanical prescription drug compound derived from the red sap of the Croton lechleri plant of Latin and South America. It is indicated as an anti-diarrheal for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy. Crofelemer does not affect gut motility and is not absorbed systemically to any significant level. It instead acts locally, inhibiting the secretion of chloride ions via the cystic fibrosis transmembrane regulator (CFTR) chloride channels and the calcium-activated chloride channels (CaCC) from the luminal membrane of intestinal cells. By blocking these channels, crofelemer reduces gastrointestinal fluid accumulation. Crofelemer received initial FDA approval in December 2012.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer with or without food.
-Swallow the tablets whole; do not cut, chew, or crush.
During clinical evaluation of crofelemer therapy, a total of 696 HIV-positive patients in 3 placebo-controlled trials received crofelemer for a mean duration of 78 days. Study doses varied across the three trials, with doses ranging from 125 mg twice daily to 500 mg four times daily. Gastrointestinal (GI) adverse reactions that occurred in at least 2% of patients taking a 125 mg daily dose of crofelemer and at a higher incidence than placebo included: flatulence (3.1% vs. 1.1%), hyperbilirubinemia (increased bilirubin, 3.1% vs. 1.1%), elevated hepatic enzymes [increased alanine aminotransferase (2.2%-3.1% vs. 1.1%)], nausea (2.6% vs. 1.5%), hemorrhoids (2.2% vs. 0%), giardiasis (2.2% vs. 0%), and abdominal distension (2.2% vs. 0.4%). In addition, GI adverse reactions that occurred in 1-2% of patients taking a 250 mg daily dose of crofelemer included: abdominal pain, elevated hepatic enzymes (increased aspartate aminotransferase), hyperbilirubinemia (increased conjugated bilirubin, increased unconjugated bilirubin), constipation, xerostomia, dyspepsia, and gastroenteritis. Adverse reactions were similar in patients who received doses greater than 250 mg daily.
During clinical evaluation of crofelemer therapy, a total of 696 HIV-positive patients in 3 placebo-controlled trials received crofelemer for a mean duration of 78 days. Study doses varied across the three trials, with doses ranging from 125 mg twice daily to 500 mg four times daily. Respiratory adverse reactions that occurred in at least 2% of patients taking a 125 mg daily dose of crofelemer and at a higher incidence than placebo included: upper respiratory tract infection (5.7% vs. 1.5%), bronchitis (3.9% vs. 0%), cough (3.5% vs. 1.1%), and naso-pharyngitis (2.2% vs. 0.7%). In addition, adverse reactions that occurred in 1-2% of patients taking a 250 mg daily dose of crofelemer included: seasonal allergy and sinusitis. Adverse reactions were similar in patients who received doses greater than 250 mg daily.
During clinical evaluation of crofelemer therapy, a total of 696 HIV-positive patients in 3 placebo-controlled trials received crofelemer for a mean duration of 78 days. Study doses varied across the three trials, with doses ranging from 125 mg twice daily to 500 mg four times daily. Adverse reactions that occurred in at least 2% of patients taking a 125 mg daily dose of crofelemer and at a higher incidence than placebo included: back pain (2.6% vs. 1.5%), arthralgia (2.6% vs. 0%), urinary tract infection (2.2% vs. 0.7%), musculoskeletal pain (2.2% vs. 0.4%), and anxiety (2.2% vs. 0.4%). In addition, adverse reactions that occurred in 1-2% of patients taking a 250 mg daily dose of crofelemer included: acne vulgaris, contact dermatitis, depression, dizziness, herpes zoster, leukopenia, nephrolithiasis, pain in extremity, pollakiuria (increased urinary frequency), and procedural pain. Adverse reactions were similar in patients who received doses greater than 250 mg daily.
During clinical evaluation of crofelemer, patients with a history of ulcerative colitis, Crohn's disease, celiac sprue (gluten-enteropathy), chronic pancreatitis, malabsorption syndrome, or any other GI disease associated with diarrhea were excluded. Therefore, it may be prudent to avoid the use of crofelemer in these patients until more is known about any potential differences in the effects of therapy in patients with the above concomitant conditions.
There are no adequate and well-controlled studies regarding the use of crofelemer during pregnancy. This drug is minimally absorbed systemically following oral administration; therefore, maternal use is not expected to result in fetal drug exposure. Reproduction studies performed with crofelemer in rats at oral doses up to 177-times the recommended daily human dose of 250 mg (approximately 4.2 mg/kg) revealed no evidence of impaired fertility or harm to the fetus. In pregnant rabbits, doses 96-times above the recommended human dose caused abortions and resorptions of fetuses. However, it is not clear whether these effects were directly related to the maternal toxicity that was observed.
There are no data regarding the presence of crofelemer in human milk, the effects on the breast-fed infant, or the effects on milk production. To reduce the risk of postnatal transmission, HIV-infected mothers within the United States are advised by the Centers for Disease Control and Prevention to avoid breast-feeding; this recommendation applies to both untreated women and women who are receiving antiretroviral therapy.
The safety and effectiveness of crofelemer in neonates, infants, children and adolescents have not been established.
Crofelemer is indicated for the symptomatic treatment of non-infectious diarrhea. Crofelemer is not FDA-approved for the treatment of diarrhea associated with infection. In clinical trials, patients were excluded if they had diarrhea caused by organisms that penetrate the intestinal mucosa such as multiple bacteria (Salmonella, Shigella, Campylobacter, Yersinia, Mycobacterium), bacterial toxins (Clostridium difficile), ova and parasites (Giardia, Entamoeba, Isospora, Cyclospora, Cryptosporidium, Microsporidium), or viruses (Cytomegalovirus), or diarrhea due to pseudomembranous colitis associated with broad spectrum antibiotics. Diarrhea of infectious etiology should be ruled out and appropriate anti-infective therapy initiated before crofelemer treatment is considered.
In the randomized clinical trial, no differences in response to treatment were observed between subjects with varying duration of diarrhea, baseline number of daily watery bowel movements, use of protease inhibitors, CD4 cell count or age. Among race subgroups, there were no differences in the consistency of the crofelemer treatment effect except for a subgroup of Black patients; crofelemer was comparatively less effective in African Americans than non-African Americans. There were too few females (85% of subjects were male) and patients with an HIV viral load greater than 400 copies/mL to adequately assess differences in effects in these populations.
For the symptomatic relief of non-infectious diarrhea in patients with HIV-infection/AIDS receiving anti-retroviral therapy:
Oral dosage (delayed-release tablets, e.g., Mytesi):
Adults: 125 mg PO twice daily, taken with or without food. LIMITATION OF USE: Before initiating crofelemer, rule out infectious etiologies of diarrhea.
Maximum Dosage Limits:
-Adults
250 mg/day PO.
-Geriatric
250 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustment in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Acetaminophen; Codeine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Acetaminophen; Hydrocodone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Acetaminophen; Oxycodone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Alfentanil: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Alosetron: (Contraindicated) Serious and life-threatening constipation and bowel obstruction has been reported in IBS patients taking alosetron in combination with other agents to control diarrhea. The mechanism is pharmacodynamic additive constipation. Patients who have previously been on alosetron should discontinue this medication prior to taking crofelemer.
Anticholinergics: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Antidiarrheals: (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Aspirin, ASA; Oxycodone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Atropine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Atropine; Difenoxin: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration. (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
Belladonna; Opium: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration. (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Benzhydrocodone; Acetaminophen: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Benztropine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Bismuth Subsalicylate: (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Celecoxib; Tramadol: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Chlordiazepoxide; Clidinium: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Chlorpheniramine; Codeine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Chlorpheniramine; Hydrocodone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Codeine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Codeine; Guaifenesin: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Codeine; Phenylephrine; Promethazine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Codeine; Promethazine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Dicyclomine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Diphenoxylate; Atropine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration. (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
Fentanyl: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Flavoxate: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Glycopyrrolate: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Glycopyrrolate; Formoterol: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Homatropine; Hydrocodone: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration. (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Hydrocodone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Hydrocodone; Ibuprofen: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Hydromorphone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Hyoscyamine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Ibuprofen; Oxycodone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Indacaterol; Glycopyrrolate: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Levorphanol: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Loperamide: (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
Loperamide; Simethicone: (Moderate) Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
Lubiprostone: (Moderate) Crofelemer, through its local effects as an antidiarrheal on chloride channels in the intestine, may theoretically antagonize the pharmacologic effects of lubiprostone. In general, it would be illogical to concurrently administer crofelemer in combination with lubiprostone. While lubiprostone may cause diarrhea as a side effect, drug discontinuation alone may resolve the diarrhea.
Meperidine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Methadone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Methscopolamine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Morphine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Morphine; Naltrexone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Neostigmine; Glycopyrrolate: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Oliceridine: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Opiate Agonists: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Oxybutynin: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Oxycodone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Oxymorphone: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Propantheline: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Remifentanil: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Scopolamine: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Sufentanil: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Tapentadol: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Tramadol: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Tramadol; Acetaminophen: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Trihexyphenidyl: (Moderate) Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration.
Crofelemer is an inhibitor of both the cyclic adenosine monophosphate (cAMP)-stimulated cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion channel, and the calcium-activated chloride ion channels (CaCC) at the luminal membrane of enterocytes. These channels regulate fluid secretion by intestinal epithelial cells. Crofelemer acts by blocking the channels and accompanying high volume water loss in diarrhea, normalizing the flow of chloride ions and water in the GI tract.
Crofelemer is administered orally. Distribution has not been determined. No metabolites have been identified in healthy subjects or patients in clinical trials. The elimination route has not been identified in humans.
Affected cytochrome P450 isoenzymes and drug transporter: none
In vitro studies indicated that crofelemer has the potential to inhibit cytochrome P450 isoenzyme 3A and transporters MRP2 and OATP1A2 at concentrations expected in the gut. However, due to its minimal absorption, it is not likely to inhibit cytochrome P450 isoenzymes systemically.
-Route-Specific Pharmacokinetics
Oral Route
The absorption of crofelemer is minimal following oral dosing in healthy adults and HIV-positive patients and concentrations of crofelemer in plasma are below the level of quantitation (i.e., < 50 ng/mL). Therefore, standard pharmacokinetic parameters such as area under the curve (AUC), maximum concentration (Cmax), and half-life cannot be estimated.
-Special Populations
Pediatrics
There are no pediatric data.
Geriatric
Clinical studies with crofelemer did not include sufficient numbers of geriatric patients aged 65 and over to determine whether they respond differently than younger adults.
Gender Differences
In the randomized clinical trial, there were too few females (85% of subjects were male) to adequately assess differences in the effects of crofelemer therapy.
Ethnic Differences
In the randomized clinical trial, there were no differences in the consistency of the crofelemer treatment effect except for the subgroup of African-Americans; crofelemer was comparatively less effective in African-American patients than non-African Americans.