VERZENIO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VERZENIO (VERZENIO).

How it works

Selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which prevents phosphorylation of retinoblastoma protein, blocking cell cycle progression from G1 to S phase and reducing cancer cell proliferation.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein (P-gp).
Excretion	Primarily fecal (≥91%) as unchanged parent drug and metabolites; renal excretion accounts for <1%.
Half-life	Terminal elimination half-life is approximately 18 hours; supports once-daily dosing. Clinically, steady-state is achieved within 5 days.
Protein binding	~96% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
Volume of Distribution	Approximately 108 L (1.54 L/kg for a 70 kg patient); indicates extensive tissue distribution.
Bioavailability	~45% (oral); not significantly affected by food.
Onset of Action	Oral administration: clinical effect on tumor growth occurs within days to weeks; measurable pharmacodynamic effect on CDK4/6 activity within 4 hours.
Duration of Action	Duration of CDK4/6 inhibition persists for at least 24 hours with once-daily dosing; continuous suppression of Rb phosphorylation is maintained.

Classification & Brands

Dosing & administration

150 mg orally twice daily.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 100 mg twice daily.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 100 mg twice daily. Child-Pugh C: not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment recommended; monitor for increased toxicity due to age-related renal or hepatic decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VERZENIO (VERZENIO).

Breastfeeding

It is not known whether abemaciclib is excreted in human milk. However, due to the potential for serious adverse reactions in nursing infants, women should not breastfeed during treatment and for at least 3 weeks after the last dose. M/P ratio is not available.

Teratogenic Risk

Abemaciclib is an FDA Pregnancy Category D drug. Based on its mechanism of action (CDK4/6 inhibition) and animal studies showing embryotoxicity and teratogenicity, there is a risk of fetal harm. In the first trimester, there is potential for major congenital malformations; in the second and third trimesters, risk of fetal growth restriction, oligohydramnios, and fetal death. Use is contraindicated in pregnancy.

Warnings & precautions

■ FDA Black Box Warning

There is no FDA black box warning for VERZENIO.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with strong CYP3A4 inducers","Pre-existing severe neutropenia (absolute neutrophil count <1000/mm3)"]

Clinical Precautions

Precautions

["Interstitial lung disease (ILD)/pneumonitis may occur; monitor for pulmonary symptoms","Decrease in absolute neutrophil count (neutropenia) may occur; monitor blood counts","Hepatotoxicity; monitor liver function tests","Risk of venous thromboembolism (VTE); monitor for signs and symptoms","Fetal harm based on animal studies; advise effective contraception"]

Clinical Tips & Counseling

Drug interactions

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VERZENIO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VERZENIO (VERZENIO).

How it works

What the body does with it

Metabolism	Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein (P-gp).
Excretion	Primarily fecal (≥91%) as unchanged parent drug and metabolites; renal excretion accounts for <1%.
Half-life	Terminal elimination half-life is approximately 18 hours; supports once-daily dosing. Clinically, steady-state is achieved within 5 days.
Protein binding	~96% bound to plasma proteins (primarily albumin and α1-acid glycoprotein).
Volume of Distribution	Approximately 108 L (1.54 L/kg for a 70 kg patient); indicates extensive tissue distribution.
Bioavailability	~45% (oral); not significantly affected by food.
Onset of Action	Oral administration: clinical effect on tumor growth occurs within days to weeks; measurable pharmacodynamic effect on CDK4/6 activity within 4 hours.
Duration of Action	Duration of CDK4/6 inhibition persists for at least 24 hours with once-daily dosing; continuous suppression of Rb phosphorylation is maintained.

Classification & Brands

Dosing & administration

150 mg orally twice daily.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), reduce dose to 100 mg twice daily.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 100 mg twice daily. Child-Pugh C: not recommended.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment recommended; monitor for increased toxicity due to age-related renal or hepatic decline.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for VERZENIO (VERZENIO).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

There is no FDA black box warning for VERZENIO.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with strong CYP3A4 inducers","Pre-existing severe neutropenia (absolute neutrophil count <1000/mm3)"]