FAYOSIM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FAYOSIM (FAYOSIM).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FAYOSIM (FAYOSIM).

Breastfeeding	Contraindicated during breastfeeding. M/P ratio unknown; FAYOSIM is excreted into breast milk in animal studies. Risk of serious adverse reactions in nursing infants.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Patients less than 2 years of age (black box warning).","Known or suspected mechanical gastrointestinal obstruction.","History of hypersensitivity to plecanatide or any excipient in FAYOSIM."]

Clinical Precautions

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."]

Clinical Tips & Counseling

Drug interactions

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FAYOSIM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FAYOSIM (FAYOSIM).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FAYOSIM (FAYOSIM).

Breastfeeding	Contraindicated during breastfeeding. M/P ratio unknown; FAYOSIM is excreted into breast milk in animal studies. Risk of serious adverse reactions in nursing infants.
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.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Patients less than 2 years of age (black box warning).","Known or suspected mechanical gastrointestinal obstruction.","History of hypersensitivity to plecanatide or any excipient in FAYOSIM."]