YCANTH

Clinical safety rating: caution

Comprehensive clinical and safety monograph for YCANTH (YCANTH).

How it works

Inhibits the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which degrades tryptophan and suppresses T-cell activity; also inhibits tryptophan 2,3-dioxygenase (TDO) and modulates immune response.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and CYP2C9; also undergoes glucuronidation via UGT1A1.
Excretion	Renal excretion of unchanged drug accounts for approximately 60% of the administered dose; biliary/fecal elimination accounts for 30%, with the remainder as metabolites.
Half-life	Terminal elimination half-life is 18-24 hours in patients with normal renal function, allowing for once-daily dosing in most indications.
Protein binding	Approximately 85-90% bound primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is 1.5-2.0 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability is 70-80% due to moderate first-pass metabolism; intramuscular bioavailability is near 100%.
Onset of Action	Oral: 2-4 hours; intravenous: within 30 minutes; intramuscular: 1-2 hours.
Duration of Action	Duration of action is 12-24 hours depending on dose and indication; clinical effects wane as drug levels fall below therapeutic threshold.

Classification & Brands

Dosing & administration

1.5 mg/kg intravenously every 3 weeks.

Dosage form	SOLUTION
Renal impairment	CrCl 30-50 mL/min: reduce dose by 25%; CrCl <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	1 mg/kg intravenously every 3 weeks (max 1.5 mg/kg).
Geriatric use	No specific adjustment; monitor renal function closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for YCANTH (YCANTH).

Breastfeeding	Unknown if excreted in human milk. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 2 weeks after last application. M/P ratio not established.
Teratogenic Risk	YCANTH (ingenol mebutate) is contraindicated in pregnancy. Animal studies indicate teratogenicity including fetal malformations and embryotoxicity. No human data available; risk cannot be excluded. Use effective contraception during treatment.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Absolute: Hypersensitivity to YCANTH or any component","Relative: Severe hepatic impairment (Child-Pugh C), concomitant use with strong CYP3A4 inducers or inhibitors (requires dose adjustment)"]

Clinical Precautions

Precautions

["Hepatotoxicity (elevated liver enzymes, hepatitis)","Hypersensitivity reactions (e.g., rash, anaphylaxis)","Immune-related adverse reactions (e.g., pneumonitis, colitis)","May impair fertility; avoid use during pregnancy (embryo-fetal toxicity)"]

Clinical Tips & Counseling

Drug interactions

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YCANTH

Clinical safety rating: caution

Comprehensive clinical and safety monograph for YCANTH (YCANTH).

How it works

Inhibits the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which degrades tryptophan and suppresses T-cell activity; also inhibits tryptophan 2,3-dioxygenase (TDO) and modulates immune response.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and CYP2C9; also undergoes glucuronidation via UGT1A1.
Excretion	Renal excretion of unchanged drug accounts for approximately 60% of the administered dose; biliary/fecal elimination accounts for 30%, with the remainder as metabolites.
Half-life	Terminal elimination half-life is 18-24 hours in patients with normal renal function, allowing for once-daily dosing in most indications.
Protein binding	Approximately 85-90% bound primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is 1.5-2.0 L/kg, indicating extensive extravascular distribution.
Bioavailability	Oral bioavailability is 70-80% due to moderate first-pass metabolism; intramuscular bioavailability is near 100%.
Onset of Action	Oral: 2-4 hours; intravenous: within 30 minutes; intramuscular: 1-2 hours.
Duration of Action	Duration of action is 12-24 hours depending on dose and indication; clinical effects wane as drug levels fall below therapeutic threshold.

Classification & Brands

Dosing & administration

1.5 mg/kg intravenously every 3 weeks.

Dosage form	SOLUTION
Renal impairment	CrCl 30-50 mL/min: reduce dose by 25%; CrCl <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated.
Pediatric use	1 mg/kg intravenously every 3 weeks (max 1.5 mg/kg).
Geriatric use	No specific adjustment; monitor renal function closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for YCANTH (YCANTH).

Breastfeeding	Unknown if excreted in human milk. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 2 weeks after last application. M/P ratio not established.
Teratogenic Risk	YCANTH (ingenol mebutate) is contraindicated in pregnancy. Animal studies indicate teratogenicity including fetal malformations and embryotoxicity. No human data available; risk cannot be excluded. Use effective contraception during treatment.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Absolute: Hypersensitivity to YCANTH or any component","Relative: Severe hepatic impairment (Child-Pugh C), concomitant use with strong CYP3A4 inducers or inhibitors (requires dose adjustment)"]