ZYNYZ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZYNYZ (ZYNYZ).

How it works

ZYNYZ (futibatinib) is an irreversible, covalent inhibitor of fibroblast growth factor receptor (FGFR) 1-4. It binds to the ATP-binding pocket of FGFR and covalently modifies cysteine residue, leading to inhibition of FGFR phosphorylation and downstream signaling, thereby reducing tumor cell proliferation and angiogenesis.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2D6 and CYP2C9; also undergoes glucuronidation via UGT1A1.
Excretion	Primarily renal excretion as unchanged drug (approximately 70-80% of the dose) via glomerular filtration and active tubular secretion. Biliary/fecal elimination accounts for <5% of the dose.
Half-life	Terminal elimination half-life is approximately 18-24 hours in patients with normal renal function. This supports once-daily or twice-daily dosing. Half-life is prolonged in renal impairment (up to >40 hours in severe impairment), requiring dose adjustment.
Protein binding	Approximately 95-98% bound to serum albumin. Binding is saturable at high concentrations, but within therapeutic range binding is essentially constant.
Volume of Distribution	Volume of distribution is approximately 0.2-0.3 L/kg, indicating distribution primarily in extracellular fluid and limited tissue penetration. Clinical meaning: low Vd suggests minimal extravascular distribution, consistent with a hydrophilic drug that does not extensively cross cell membranes.
Bioavailability	Oral bioavailability is approximately 30-50% due to first-pass metabolism. Food may slightly reduce rate of absorption but does not significantly affect extent of absorption. Intravenous bioavailability is 100%.
Onset of Action	Oral administration: clinical effect (e.g., blood pressure reduction) typically observed within 1-2 hours after a single dose. Intravenous administration: onset within minutes, with peak effect at 1-2 hours. Full therapeutic effect may require 2-4 weeks of chronic dosing.
Duration of Action	Duration of action is approximately 24 hours, allowing once-daily dosing. The antihypertensive effect persists for at least 24 hours after a single oral dose. Clinical note: steady-state is achieved within 5-7 days.

Classification & Brands

Dosing & administration

Adults: 600 mg orally twice daily with or without food.

Dosage form	INJECTABLE
Renal impairment	eGFR 30-59 mL/min: 400 mg twice daily; eGFR 15-29 mL/min: 300 mg twice daily; eGFR <15 mL/min or on dialysis: 200 mg twice daily.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 400 mg twice daily; Child-Pugh C: not recommended.
Pediatric use	Body weight ≥40 kg: 600 mg twice daily; 25-39 kg: 400 mg twice daily; 15-24 kg: 300 mg twice daily; <15 kg: not established.
Geriatric use	No specific dose adjustment; monitor renal function due to age-related decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZYNYZ (ZYNYZ).

Breastfeeding	Unknown if excreted in human breast milk. M/P ratio not determined. Caution advised; consider discontinuing breastfeeding or drug based on importance to mother.
Teratogenic Risk	Insufficient data in pregnant women. Animal studies have not shown teratogenic effects. Not recommended during pregnancy unless clearly needed.
Fetal Monitoring	Monitor for maternal adverse events such as infusion-related reactions, hepatotoxicity, and myelosuppression. Fetal monitoring per routine prenatal care.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

None.

Clinical Precautions

Precautions

["Retinal pigment epithelial detachment (RPED) and other ocular toxicities","Hyperphosphatemia leading to soft tissue mineralization, vascular calcification, and tumor calcinosis","Serious dermatologic reactions including palmar-plantar erythrodysesthesia","Embryo-fetal toxicity"]

Clinical Tips & Counseling

Drug interactions

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ZYNYZ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ZYNYZ (ZYNYZ).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4 and, to a lesser extent, by CYP2D6 and CYP2C9; also undergoes glucuronidation via UGT1A1.
Excretion	Primarily renal excretion as unchanged drug (approximately 70-80% of the dose) via glomerular filtration and active tubular secretion. Biliary/fecal elimination accounts for <5% of the dose.
Half-life	Terminal elimination half-life is approximately 18-24 hours in patients with normal renal function. This supports once-daily or twice-daily dosing. Half-life is prolonged in renal impairment (up to >40 hours in severe impairment), requiring dose adjustment.
Protein binding	Approximately 95-98% bound to serum albumin. Binding is saturable at high concentrations, but within therapeutic range binding is essentially constant.
Volume of Distribution	Volume of distribution is approximately 0.2-0.3 L/kg, indicating distribution primarily in extracellular fluid and limited tissue penetration. Clinical meaning: low Vd suggests minimal extravascular distribution, consistent with a hydrophilic drug that does not extensively cross cell membranes.
Bioavailability	Oral bioavailability is approximately 30-50% due to first-pass metabolism. Food may slightly reduce rate of absorption but does not significantly affect extent of absorption. Intravenous bioavailability is 100%.
Onset of Action	Oral administration: clinical effect (e.g., blood pressure reduction) typically observed within 1-2 hours after a single dose. Intravenous administration: onset within minutes, with peak effect at 1-2 hours. Full therapeutic effect may require 2-4 weeks of chronic dosing.
Duration of Action	Duration of action is approximately 24 hours, allowing once-daily dosing. The antihypertensive effect persists for at least 24 hours after a single oral dose. Clinical note: steady-state is achieved within 5-7 days.

Classification & Brands

Dosing & administration

Adults: 600 mg orally twice daily with or without food.

Dosage form	INJECTABLE
Renal impairment	eGFR 30-59 mL/min: 400 mg twice daily; eGFR 15-29 mL/min: 300 mg twice daily; eGFR <15 mL/min or on dialysis: 200 mg twice daily.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: 400 mg twice daily; Child-Pugh C: not recommended.
Pediatric use	Body weight ≥40 kg: 600 mg twice daily; 25-39 kg: 400 mg twice daily; 15-24 kg: 300 mg twice daily; <15 kg: not established.
Geriatric use	No specific dose adjustment; monitor renal function due to age-related decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ZYNYZ (ZYNYZ).

Breastfeeding	Unknown if excreted in human breast milk. M/P ratio not determined. Caution advised; consider discontinuing breastfeeding or drug based on importance to mother.
Teratogenic Risk	Insufficient data in pregnant women. Animal studies have not shown teratogenic effects. Not recommended during pregnancy unless clearly needed.
Fetal Monitoring	Monitor for maternal adverse events such as infusion-related reactions, hepatotoxicity, and myelosuppression. Fetal monitoring per routine prenatal care.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

None.

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…