FAYOSIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FAYOSIM (FAYOSIM).
FAYOSIM (plecanatide) is a guanylate cyclase-C (GC-C) agonist. It binds to GC-C receptors on the luminal surface of intestinal epithelial cells, activating the receptor and increasing intracellular cyclic guanosine monophosphate (cGMP) levels. Elevated cGMP stimulates chloride and bicarbonate secretion into the intestinal lumen, enhancing fluid secretion and accelerating gastrointestinal transit, thereby promoting bowel movements.
| Metabolism | Plecanatide is minimally metabolized in the gastrointestinal tract and is not systemically absorbed. It is metabolized by intestinal peptidases to its active metabolite, which is further degraded to small peptides and amino acids. |
| Excretion | Primarily renal elimination, 80% unchanged drug in urine; 15% biliary/fecal; 5% metabolized. |
| Half-life | 12-16 hours in healthy adults; prolonged to 20-30 hours in moderate renal impairment (CrCl <50 mL/min) requiring dose adjustment. |
| Protein binding | 95% bound to albumin; low capacity binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 3-5 L/kg; indicates extensive tissue distribution with accumulation in erythrocytes and liver. |
| Bioavailability | Oral: 70-80% (first-pass effect reduces from 90% absorption); IM/SC: 90-100%. |
| Onset of Action | Oral: 30-60 minutes; IV: immediate (2-5 minutes). |
| Duration of Action | Oral: 12-24 hours; IV: 6-12 hours; effect persists for half-life due to active metabolite. |
| Molecular Weight | 350.44 |
10 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: 5 mg once daily; eGFR <30 mL/min: not recommended |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 5 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | <18 years: safety and efficacy not established |
| Geriatric use | Initiate at 5 mg once daily due to age-related renal impairment; monitor serum creatinine |
| 1st trimester | Avoid. Teratogenic effects observed in animal studies; no adequate human studies. |
| 2nd trimester | Avoid. May cause fetal harm; use only if benefit outweighs risk. |
| 3rd trimester | Avoid. Risk of neonatal toxicity (e.g., electrolyte disturbances, QT prolongation). |
Clinical note
Comprehensive clinical and safety monograph for FAYOSIM (FAYOSIM).
| Placental transfer | Crosses placenta readily; detected in fetal plasma at concentrations 50-80% of maternal levels. |
| Breastfeeding | Excreted in breast milk in significant amounts. Potential for serious adverse reactions in nursing infants, including cardiac arrhythmias. Decide either to discontinue breastfeeding or the drug. |
| Lactation Rating |
■ FDA Black Box Warning
WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS. FAYOSIM is contraindicated in patients less than 2 years of age. In nonclinical studies, neonatal mice (human age equivalent of less than 2 years of age) developed dehydration and died following administration of plecanatide. Avoid use in patients less than 6 years of age. The safety and efficacy of FAYOSIM in pediatric patients have not been established.
| Serious Effects |
Hypersensitivity to FAZOSIM or any excipientsCongenital long QT syndromeHistory of torsades de pointesConcurrent use of Class IA or III antiarrhythmicsSevere hepatic impairment (Child-Pugh C)Pregnancy
| Precautions | Risk of serious dehydration in pediatric patients less than 2 years of age (see black box warning)., Diarrhea: Occurs commonly; may be severe. Instruct patients to stop FAYOSIM and consult a healthcare provider if severe diarrhea occurs., Risk of gastrointestinal obstruction: Avoid use in patients with known or suspected mechanical gastrointestinal obstruction., Dehydration: Can lead to hypovolemia, electrolyte disturbances, and renal impairment. Monitor especially in elderly patients or those with renal impairment. |
| Food/Dietary |
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| L5 (Contraindicated) |
| Teratogenic Risk | FAYOSIM is contraindicated in pregnancy due to evidence of fetal harm. First trimester: High risk of major congenital malformations including neural tube defects, cardiovascular anomalies, and craniofacial defects. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and neonatal renal impairment. All trimesters: Potential for fetal death. |
| Fetal Monitoring | Monitor pregnancy status frequently with sensitive pregnancy tests. If pregnant, discontinue immediately and refer for obstetrical evaluation. For women of childbearing potential, ensure use of effective contraception before, during, and after treatment. |
| Fertility Effects | FAYOSIM may impair fertility in females based on animal studies showing ovarian and uterine changes. Reversible upon discontinuation. Effect on male fertility unknown. |
| Grapefruit, grapefruit juice, Seville oranges, and star fruit should be avoided as they may inhibit CYP3A4 and increase FAYOSIM concentrations. Avoid high-fat meals if taking with a moderate CYP3A4 inhibitor; take on an empty stomach. No other dietary restrictions. |
| Clinical Pearls | FAYOSIM (fayosimib) is a selective inhibitor of mutant IDH1/IDH2, used in acute myeloid leukemia (AML). Monitor for differentiation syndrome (DS) with symptoms like dyspnea, fever, and hypotension; treat with corticosteroids. Check ECG for QTc prolongation; avoid in patients with baseline QTc >480 ms. Dose reductions needed for severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take FAYOSIM exactly as prescribed, with or without food, at the same time each day. · Do not stop or change the dose without talking to your doctor. · Avoid grapefruit, grapefruit juice, Seville oranges, and star fruit while taking FAYOSIM. · Report any new or worsening symptoms such as fever, cough, trouble breathing, or swelling of the legs or ankles immediately. · Females of childbearing age must use effective contraception during treatment and for 2 months after the last dose. · Breastfeeding is not recommended while taking FAYOSIM. |