NILOTINIB HYDROCHLORIDE

Clinical safety rating: avoid

Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause QT prolongation and sudden death.

How it works

Bcr-Abl tyrosine kinase inhibitor; specifically binds to and inhibits the kinase activity of Bcr-Abl, leading to inhibition of proliferation and induction of apoptosis in Bcr-Abl positive cells.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also a substrate of CYP2C8, CYP2C9, CYP2D6, and UGT1A1.
Excretion	Primarily fecal (≥90%); renal excretion accounts for <5% as unchanged drug and metabolites.
Half-life	Terminal elimination half-life is approximately 17 hours (range 15-22 hours), supporting twice-daily dosing.
Protein binding	Approximately 98-99% bound to human serum albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Steady-state volume of distribution is about 2.2 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 30% (range 20-40%) when taken on an empty stomach; food increases exposure.
Onset of Action	Not applicable; clinical effect (e.g., hematologic response) typically observed after 1-2 months of continuous oral therapy.
Duration of Action	Duration of cytogenetic response persists with continued dosing; effect wanes upon discontinuation.

Classification & Brands

Dosing & administration

400 mg orally twice daily, approximately 12 hours apart, with food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CLcr ≥30 mL/min). For severe renal impairment (CLcr <30 mL/min), use with caution and reduce dose to 300 mg twice daily.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce initial dose to 300 mg twice daily. Child-Pugh C: Reduce initial dose to 200 mg twice daily.
Pediatric use	Not approved for use in pediatric patients.
Geriatric use	No specific dose adjustment required, but monitor for adverse effects (e.g., QT prolongation, electrolyte disturbances) due to increased sensitivity.

Use during pregnancy

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

Clinical note

Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause QT prolongation and sudden death.

FDA category	Contraindicated
Breastfeeding	It is unknown if nilotinib is excreted in human milk. The M/P ratio has not been determined. Due to the potential for serious adverse effects in nursing infants, breastfeeding is not recommended during therapy and for at least 14 days after the last dose.
Teratogenic Risk	Based on animal studies, nilotinib is embryotoxic and fetotoxic. Use in pregnant women may cause fetal harm, including increased risk of fetal death, skeletal anomalies, and reduced fetal weight. There are no adequate human studies. Risk cannot be excluded in the first trimester. Second and third trimester exposure may also pose risks of growth restriction and developmental abnormalities.

Warnings & precautions

■ FDA Black Box Warning

Corrected QT interval (QTc) prolongation and sudden death; do not use in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Avoid strong CYP3A4 inhibitors and grapefruit products.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypokalemia; hypomagnesemia; long QT syndrome; concomitant use with strong CYP3A4 inhibitors or grapefruit products; hypersensitivity to nilotinib or any component of the formulation.

Clinical Precautions

Precautions

QTc prolongation; myelosuppression; hepatotoxicity; pancreatitis; fluid retention; elevated lipase; electrolyte abnormalities; tumor lysis syndrome; fetal harm.

Clinical Tips & Counseling

Drug interactions

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NILOTINIB HYDROCHLORIDE

Clinical safety rating: avoid

Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause QT prolongation and sudden death.

How it works

Bcr-Abl tyrosine kinase inhibitor; specifically binds to and inhibits the kinase activity of Bcr-Abl, leading to inhibition of proliferation and induction of apoptosis in Bcr-Abl positive cells.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also a substrate of CYP2C8, CYP2C9, CYP2D6, and UGT1A1.
Excretion	Primarily fecal (≥90%); renal excretion accounts for <5% as unchanged drug and metabolites.
Half-life	Terminal elimination half-life is approximately 17 hours (range 15-22 hours), supporting twice-daily dosing.
Protein binding	Approximately 98-99% bound to human serum albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Steady-state volume of distribution is about 2.2 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 30% (range 20-40%) when taken on an empty stomach; food increases exposure.
Onset of Action	Not applicable; clinical effect (e.g., hematologic response) typically observed after 1-2 months of continuous oral therapy.
Duration of Action	Duration of cytogenetic response persists with continued dosing; effect wanes upon discontinuation.

Classification & Brands

Dosing & administration

400 mg orally twice daily, approximately 12 hours apart, with food.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CLcr ≥30 mL/min). For severe renal impairment (CLcr <30 mL/min), use with caution and reduce dose to 300 mg twice daily.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce initial dose to 300 mg twice daily. Child-Pugh C: Reduce initial dose to 200 mg twice daily.
Pediatric use	Not approved for use in pediatric patients.
Geriatric use	No specific dose adjustment required, but monitor for adverse effects (e.g., QT prolongation, electrolyte disturbances) due to increased sensitivity.

Use during pregnancy

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

Clinical note

Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause QT prolongation and sudden death.

FDA category	Contraindicated
Breastfeeding	It is unknown if nilotinib is excreted in human milk. The M/P ratio has not been determined. Due to the potential for serious adverse effects in nursing infants, breastfeeding is not recommended during therapy and for at least 14 days after the last dose.
Teratogenic Risk	Based on animal studies, nilotinib is embryotoxic and fetotoxic. Use in pregnant women may cause fetal harm, including increased risk of fetal death, skeletal anomalies, and reduced fetal weight. There are no adequate human studies. Risk cannot be excluded in the first trimester. Second and third trimester exposure may also pose risks of growth restriction and developmental abnormalities.

Warnings & precautions

■ FDA Black Box Warning

Corrected QT interval (QTc) prolongation and sudden death; do not use in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Avoid strong CYP3A4 inhibitors and grapefruit products.

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypokalemia; hypomagnesemia; long QT syndrome; concomitant use with strong CYP3A4 inhibitors or grapefruit products; hypersensitivity to nilotinib or any component of the formulation.

Clinical Precautions

Precautions

QTc prolongation; myelosuppression; hepatotoxicity; pancreatitis; fluid retention; elevated lipase; electrolyte abnormalities; tumor lysis syndrome; fetal harm.

Clinical Tips & Counseling

Drug interactions

Loading safety data…