MYTESI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MYTESI (MYTESI).
MYTESI (crofelemer) is a proanthocyanidin oligomer that acts locally in the gastrointestinal tract to inhibit chloride ion secretion by blocking both the cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCC) at the luminal surface of enterocytes, thereby reducing fluid and electrolyte secretion.
| Metabolism | Crofelemer undergoes minimal systemic absorption; metabolism is predominantly via hydrolysis in the gastrointestinal tract. Hepatic metabolism is negligible. |
| Excretion | Primarily fecal (82-86%) as unchanged drug; renal excretion accounts for <1% of the dose. |
| Half-life | 1.6 hours (mean terminal elimination half-life); clinical context: short half-life supports oral administration three times daily to maintain therapeutic levels. |
| Protein binding | >99% bound; primarily to albumin and α1-acid glycoprotein. |
| Volume of Distribution | 0.2 L/kg (apparent); clinical meaning: low Vd indicates limited extravascular distribution (primarily confined to plasma and intestinal lumen). |
| Bioavailability | 0.3% (oral); clinical significance: minimal systemic absorption due to efflux by P-glycoprotein and extensive first-pass metabolism; drug acts locally in the gastrointestinal tract. |
| Onset of Action | Oral: within 0.5 hours (time to detectable inhibition of secretory diarrhea); peak effect correlates with maximum plasma concentration at ~1 hour. |
| Duration of Action | Approximately 8 hours (supports thrice-daily dosing); clinical note: duration may be shorter in severe diarrhea due to rapid transit. |
| Molecular Weight | 404.48 |
1 capsule (5 mg) orally three times daily, taken 30 minutes before meals.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 5 mg twice daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment; use caution due to potential for decreased hepatic/renal function and increased sensitivity. |
| 1st trimester | Use only if potential benefit justifies risk. Animal reproduction studies have shown adverse effects (increased resorptions, reduced fetal weight) at doses >2x human exposure. No well-controlled studies in pregnant women. |
| 2nd trimester | Use only if potential benefit justifies risk. Similar safety considerations as T1; consider maternal condition and necessity of therapy. |
| 3rd trimester | Use only if potential benefit justifies risk. May cause premature closure of ductus arteriosus in fetus; avoid in third trimester if possible. |
Clinical note
Comprehensive clinical and safety monograph for MYTESI (MYTESI).
| Placental transfer | Animal studies indicate placental transfer. Human data limited; molecular weight suggests likely crossing. |
| Breastfeeding | Excretion into human milk unknown. Due to potential for serious adverse reactions in nursing infants (e.g., GI ulceration, bleeding), decision should be made whether to discontinue nursing or discontinue drug, taking into account importance of drug to mother. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to misoprostol or any componentKnown pregnancySevere hepatic impairment (Child-Pugh C)History of asthma (relative; use with caution)
| Precautions | Should not be used for infectious diarrhea unless infection has been ruled out, Not recommended for use in patients with known hypersensitivity to crofelemer or any component of the formulation |
| Food/Dietary | No known food interactions with MYTESI. |
| Clinical Pearls | MYTESI (crofelemer) is a proanthocyanidin oligomer extracted from the latex of Croton lechleri. It inhibits chloride secretion via CFTR and CaCC channels in the GI tract, reducing diarrhea. It is minimally absorbed and acts locally. Do not use for infectious diarrhea. Avoid concomitant use with strong CYP3A4 inducers (e.g., rifampin) as they may reduce crofelemer levels. Monitor for constipation in patients with slowed GI motility. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. MYTESI (crofelemer) is minimally absorbed systemically (<0.4% bioavailability), thus exposure to fetus is negligible. No teratogenic effects observed in animal reproduction studies at doses up to 32 times the human dose. FDA Pregnancy Category C (if applicable; note: MYTESI is not FDA-approved; data based on crofelemer). |
| Fetal Monitoring | No specific monitoring required beyond routine prenatal care. Monitor maternal diarrhea severity and hydration status. |
| Fertility Effects | No effects on fertility observed in animal studies at doses up to 32 times the human dose. |
| Patient Advice | Take MYTESI exactly as prescribed, usually twice daily with or without food. · Swallow tablets whole; do not crush, chew, or split. · Do not take MYTESI for diarrhea caused by infection; see your doctor if you have fever or bloody stools. · Inform your doctor if you develop severe constipation or abdominal pain. · Keep MYTESI at room temperature away from moisture and heat. |