VERZENIO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VERZENIO (VERZENIO).
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.
| 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. |
| Molecular Weight | 506.59 |
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. |
| 1st trimester | Abram Przyspieszone działanie leku VERZENIO (abemacyklib) w pierwszym trymestrze ciąży jest przeciwwskazane ze względu na ryzyko uszkodzenia płodu. Brak wystarczających danych dotyczących bezpieczeństwa; wykazano działanie teratogenne u zwierząt. |
| 2nd trimester | Stosowanie abemacyklibu w drugim trymestrze jest przeciwwskazane, ponieważ może powodować uszkodzenie płodu. Zaleca się unikanie ciąży podczas terapii. |
| 3rd trimester | W trzecim trymestrze abemacyklib jest przeciwwskazany ze względu na potencjalne ryzyko dla płodu, w tym zaburzenia wzrostu i przedwczesny poród. |
Clinical note
Comprehensive clinical and safety monograph for VERZENIO (VERZENIO).
| Placental transfer | Abemacyklib przenika przez barierę łożyskową u zwierząt; przewiduje się znaczące przenikanie u ludzi na podstawie właściwości farmakokinetycznych. |
| Breastfeeding | Brak danych dotyczących przenikania abemacyklibu do mleka ludzkiego. Ze względu na potencjalne ryzyko poważnych działań niepożądanych u karmionego piersią niemowlęcia, należy przerwać karmienie piersią podczas leczenia i przez co najmniej 1 tydzień po przyjęciu ostatniej dawki. |
■ FDA Black Box Warning
There is no FDA black box warning for VERZENIO.
| Serious Effects |
Ciężka niewydolność wątroby (Child-Pugh C)Jednoczesne stosowanie silnych inhibitorów CYP3A4 (np. ketokonazol, itrakonazol, klarytromycyna, rytonawir)Nadwrażliwość na substancję czynną lub którąkolwiek substancję pomocnicząCiąża
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice; they increase abemaciclib levels. No other food restrictions. |
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| Lactation Rating | L5 - Avoid (przeciwwskazane) |
| 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. |
| Fetal Monitoring | Monitor complete blood counts prior to starting therapy and periodically thereafter due to risk of neutropenia. Monitor liver function tests and serum creatinine. For pregnant patients, serial ultrasound assessment for fetal growth and amniotic fluid volume is recommended. Monitor for signs of thromboembolism. |
| Fertility Effects | Abemaciclib may impair fertility in males and females based on animal studies. In female rats, there was decreased fertility and embryolethality. In male rats, decreased sperm motility and concentration were observed. The effects on human fertility are unknown. |
| Clinical Pearls | VERZENIO (abemaciclib) is a CDK4/6 inhibitor indicated for HR+/HER2- advanced or metastatic breast cancer. Monitor for diarrhea—manage with antidiarrheals and dose interruption if severe. Check CBCs before starting and monthly for first 2 months then as clinically indicated; neutropenia is common. Avoid strong CYP3A4 inhibitors (e.g., ketoconazole) and inducers (e.g., rifampin) due to significant drug interactions. Dose reduction may be needed for hepatic impairment. |
| Patient Advice | Take VERZENIO exactly as prescribed, usually twice daily with or without food. · Report any new or worsening diarrhea, as it may require dose adjustment or medication. · Watch for signs of infection (fever, chills) due to low white blood cell counts; contact your doctor immediately. · Do not eat grapefruit or drink grapefruit juice while taking this medication. · Use effective birth control during treatment and for at least 3 weeks after the last dose. · Avoid taking St. John's wort, as it can make VERZENIO less effective. |