ATONCY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ATONCY (ATONCY).

How it works

Atoncy (pemigatinib) is a selective fibroblast growth factor receptor (FGFR) inhibitor. It binds to and inhibits FGFR1, FGFR2, and FGFR3, thereby blocking downstream signaling pathways involved in cell proliferation and survival.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contributions from CYP2D6 and CYP2C9.
Excretion	Primarily renal excretion as unchanged drug (approximately 70%) and as metabolites (approximately 20%); biliary/fecal excretion accounts for the remaining 10%.
Half-life	Terminal elimination half-life is approximately 12 hours (range 10-14 hours) in patients with normal renal function; prolonged to 24-36 hours in moderate renal impairment (CrCl 30-50 mL/min) and up to 48 hours in severe renal impairment (CrCl <30 mL/min).
Protein binding	Approximately 85% bound 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 approximately 60-70% due to first-pass hepatic metabolism.
Onset of Action	Oral: 30-60 minutes; Intravenous: within 5 minutes.
Duration of Action	Oral: 12-24 hours (dose-dependent); Intravenous: 12-24 hours; clinical effect may persist beyond serum levels due to tissue binding.

Classification & Brands

Dosing & administration

ATONCY (crizotinib) 250 mg orally twice daily.

Dosage form	SOLUTION
Renal impairment	GFR 30–59 mL/min: reduce dose to 200 mg orally twice daily. GFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce to 200 mg orally twice daily. Child-Pugh C: not recommended.
Pediatric use	Not approved for pediatric patients. Safety and efficacy not established.
Geriatric use	No specific dose adjustment required; monitor renal function and tolerability.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ATONCY (ATONCY).

Breastfeeding	Not recommended during breastfeeding. M/P ratio not determined; no human data on excretion in milk; potential for serious adverse reactions in nursing infants.
Teratogenic Risk	First trimester: No adequate human studies; animal studies show increased fetal resorptions and skeletal anomalies at 2-3 times human dose. Second/third trimester: Risk of premature ductus arteriosus closure and oligohydramnios after 20 weeks gestation.
Fetal Monitoring

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 visual disturbances","Hyperphosphatemia leading to soft tissue mineralization, calciphylaxis, and hypocalcemia","Embryo-fetal toxicity"]
Food/Dietary	No specific food interactions are reported. However, avoid grapefruit juice as it may affect drug metabolism via CYP3A4 (minor for adalimumab, but generally recommended to avoid with TNF inhibitors).

Clinical Tips & Counseling

Clinical Pearls

Drug interactions

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ATONCY

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ATONCY (ATONCY).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; minor contributions from CYP2D6 and CYP2C9.
Excretion	Primarily renal excretion as unchanged drug (approximately 70%) and as metabolites (approximately 20%); biliary/fecal excretion accounts for the remaining 10%.
Half-life	Terminal elimination half-life is approximately 12 hours (range 10-14 hours) in patients with normal renal function; prolonged to 24-36 hours in moderate renal impairment (CrCl 30-50 mL/min) and up to 48 hours in severe renal impairment (CrCl <30 mL/min).
Protein binding	Approximately 85% bound 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 approximately 60-70% due to first-pass hepatic metabolism.
Onset of Action	Oral: 30-60 minutes; Intravenous: within 5 minutes.
Duration of Action	Oral: 12-24 hours (dose-dependent); Intravenous: 12-24 hours; clinical effect may persist beyond serum levels due to tissue binding.

Classification & Brands

Dosing & administration

ATONCY (crizotinib) 250 mg orally twice daily.

Dosage form	SOLUTION
Renal impairment	GFR 30–59 mL/min: reduce dose to 200 mg orally twice daily. GFR <30 mL/min: not recommended.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce to 200 mg orally twice daily. Child-Pugh C: not recommended.
Pediatric use	Not approved for pediatric patients. Safety and efficacy not established.
Geriatric use	No specific dose adjustment required; monitor renal function and tolerability.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for ATONCY (ATONCY).

Breastfeeding	Not recommended during breastfeeding. M/P ratio not determined; no human data on excretion in milk; potential for serious adverse reactions in nursing infants.
Teratogenic Risk	First trimester: No adequate human studies; animal studies show increased fetal resorptions and skeletal anomalies at 2-3 times human dose. Second/third trimester: Risk of premature ductus arteriosus closure and oligohydramnios after 20 weeks gestation.
Fetal Monitoring

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 visual disturbances","Hyperphosphatemia leading to soft tissue mineralization, calciphylaxis, and hypocalcemia","Embryo-fetal toxicity"]
Food/Dietary	No specific food interactions are reported. However, avoid grapefruit juice as it may affect drug metabolism via CYP3A4 (minor for adalimumab, but generally recommended to avoid with TNF inhibitors).

Clinical Tips & Counseling

Clinical Pearls

Drug interactions

Loading safety data…