ABEMACICLIB
Clinical safety rating: caution
Abemaciclib is a selective cyclin-dependent kinase (CDK) 4 and 6 inhibitor used in combination with endocrine therapy (e.g., aromatase inhibitor or fulvestrant) for hormone receptor-positive, HER2-negative advanced or metastatic breast cancer. It is also used as monotherapy in refractory cases.
Selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6); prevents phosphorylation of retinoblastoma protein, blocking cell cycle progression from G1 to S phase.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP3A5 and flavin-containing monooxygenase (FMO3). |
| Excretion | Primarily fecal (81%) with minor renal excretion (3% unchanged). |
| Half-life | 18.3 hours (terminal). Supports once-daily dosing. |
| Protein binding | 96% bound to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | 11.3 L/kg (mean). Indicates extensive tissue distribution. |
| Bioavailability | 45% (oral, under fasting conditions). |
| Onset of Action | Not applicable; antineoplastic effect requires continuous exposure. |
| Duration of Action | Continuous; dosing schedule maintains therapeutic concentrations. |
| Molecular Weight | 506.6 |
200 mg orally twice daily (with or without food) for advanced disease; monotherapy: 200 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | Mild to moderate renal impairment (CrCl 30-89 mL/min): no dose adjustment. Severe or ESRD: not recommended due to lack of data. |
| Liver impairment | Mild (Child-Pugh A): no adjustment. Moderate (Child-Pugh B): reduce to 100 mg twice daily. Severe (Child-Pugh C): not recommended. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment, but elderly patients may have increased risk of adverse events (e.g., diarrhea, fatigue). Monitor closely. |
| 1st trimester | Abemaciclib is contraindicated in pregnancy. Based on its mechanism of action (CDK4/6 inhibition) and animal studies showing embryotoxicity and teratogenicity, there is a high risk of fetal harm. Use effective contraception during treatment and for at least 3 weeks after the last dose. |
| 2nd trimester | Contraindicated in the second trimester. Animal data demonstrate fetal malformations and growth retardation. No human data available; avoid use. |
| 3rd trimester | Contraindicated in the third trimester. Potential for fetal harm based on mechanism and animal studies. Avoid use; if exposure occurs, monitor for adverse effects. |
Clinical note
Pregnancy: There are no adequate human studies; abemaciclib is teratogenic in animals. Avoid use during pregnancy; effective contraception required for females of reproductive potential.
| Placental transfer | Abemaciclib is expected to cross the placenta based on its molecular weight (about 506.6 Da) and lipophilicity. Animal studies confirm placental transfer and fetal exposure. |
| Breastfeeding |
■ FDA Black Box Warning
None
| Common Effects | diarrhea, neutropenia, nausea, fatigue, abdominal pain, infections, decreased appetite, vomiting |
| Serious Effects | Interstitial lung disease/pneumonitis, severe diarrhea with dehydration, hepatotoxicity (elevated LFTs), neutropenia (febrile neutropenia risk), thromboembolism. |
Hypersensitivity to abemaciclib or any excipientPregnancy
| Precautions | Interstitial lung disease (ILD)/pneumonitis: monitor for pulmonary symptoms; permanently discontinue for grade 3/4 ILD, Severe diarrhea: monitor and manage with antidiarrheals, fluids, and electrolytes; dose interruption/reduction may be needed, Neutropenia: monitor complete blood counts prior to treatment and periodically; dose adjustment for grade 3/4 neutropenia, Hepatotoxicity: monitor liver function tests; dose adjustment for elevations, Venous thromboembolism (VTE): monitor for signs/symptoms; anticoagulation may be considered |
Loading safety data…
| It is not known whether abemaciclib is excreted in human breast 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. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Abemaciclib is embryotoxic and fetotoxic in animal studies. It is contraindicated in pregnancy. Based on its mechanism of action (CDK4/6 inhibition), it may cause fetal harm. First trimester: High risk of miscarriage, major malformations. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and impaired fetal development. |
| Fetal Monitoring | Pregnancy test prior to initiation. Effective contraception during treatment and for 3 weeks after last dose. Monitor for fetal growth restriction if exposure occurs; consider ultrasound for fetal wellbeing. Monitor for maternal adverse effects: neutropenia, hepatotoxicity, diarrhea, venous thromboembolism. |
| Fertility Effects | Based on animal studies, abemaciclib may impair male and female fertility. In women, it can cause menstrual irregularities, amenorrhea, and reduced ovarian function. Reversibility unknown. In men, may reduce sperm count and motility. |
| Food/Dietary |
| Avoid grapefruit, grapefruit juice, and Seville oranges (strong CYP3A4 inhibitors). No other specific dietary restrictions; take consistently with or without food. |
| Clinical Pearls | Monitor for diarrhea and manage with antidiarrheals and fluid replacement; hold dose for recurrent Grade 2 or any Grade 3 diarrhea. Check CBC before starting, every 2 weeks for first 2 months, then monthly. Avoid strong CYP3A4 inhibitors/inducers; adjust dose with moderate inhibitors. Abemaciclib can cause venous thromboembolism (VTE); monitor for signs. Dose reduction required for severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take with or without food at the same time each day. · Do not crush or split tablets; swallow whole. · Report any signs of infection, bleeding, or blood clots immediately. · Use effective contraception during treatment and for at least 3 weeks after last dose. · Avoid grapefruit, grapefruit juice, and Seville oranges. · Call your doctor if you experience severe or persistent diarrhea, nausea, or vomiting. |