Indications
Abemaciclib is a kinase inhibitor indicated:
Pharmacology
Abemaciclib is a cyclin-dependent kinase 4 and 6 inhibitor (CDK4 and CDK6). When these kinases bind to D-cyclins, they become activated. Cyclin D1 and CDK4/6 promote retinoblastoma protein (Rb) phosphorylation, cell cycle progression, and cell proliferation in estrogen receptor-positive (ER+) breast cancer cell lines. Continuous abemaciclib exposure inhibited Rb phosphorylation and prevented cell cycle progression from G1 to S phase, resulting in senescence and apoptosis. Abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens reduced tumor size in breast cancer xenograft models.
Dosage & Administration
Abemaciclib tablets are taken orally with or without food.
Interaction
CYP3A Inhibitors: Ketoconazole should not be taken concurrently. Reduce the Abemaciclib dose with concomitant use of other strong and moderate CYP3A inhibitors.
CYP3A Inducers: Avoid concomitant use of strong and moderate CYP3A inducers.
Side Effects
Diarrhea, neutropenia, nausea, abdominal pain, infections, fatigue, anemia, leukopenia, decreased appetite, vomiting, headache, alopecia, and thrombocytopenia were the most common adverse reactions (incidence 20%).
Pregnancy & Lactation
Abemaciclib may cause fetal harm when administered to a pregnant woman, according to animal studies and the mechanism of action. In animal reproduction studies, administering abemaciclib to pregnant rats during the organogenesis period caused teratogenicity and decreased fetal weight at maternal exposures comparable to human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Inform pregnant women about the potential risk to their unborn child. Females of reproductive potential should use effective contraception while taking Abemaciclib and for three weeks after the last dose.
Precautions & Warnings
Diarrhea: Abemaciclib can cause severe diarrhea, which can lead to dehydration and infection. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider.
Neutropenia: Complete blood counts should be checked before beginning Abemaciclib therapy, every two weeks for the first two months, monthly for the next two months, and as clinically indicated.
Interstitial Lung Disease (ILD)/Pneumonitis: There have been reports of severe and fatal cases of ILD/pneumonitis. Keep an eye out for clinical symptoms or radiological changes that indicate ILD/pneumonitis. Abemaciclib should be discontinued permanently in all patients with Grade 3 or 4 ILD or pneumonitis.
Hepatotoxicity: Serum transaminase levels have been found to rise. Before beginning Abemaciclib treatment, perform liver function tests (LFTs). LFTs should be checked every two weeks for the first two months, monthly for the next two months, and as clinically indicated after that.
Venous Thromboembolism: Patients should be monitored for signs and symptoms of thrombosis and pulmonary embolism and treated as needed.
Embryo-Fetal Toxicity: May result in fetal harm. Inform patients about potential risks.
Use in Special Populations
Pediatric Use: Abemaciclib’s safety and effectiveness in pediatric patients have not been established.
Geriatric Use: There were no overall differences in Abemaciclib safety or effectiveness between these patients and younger patients.
Renal Impairment: Patients with mild or moderate renal impairment do not require any dosage adjustments.
Hepatic Impairment: In patients with mild or moderate hepatic impairment, no dosage adjustments are required.
Therapeutic Class
Protein kinase inhibitor
Storage Conditions
Keep below 30°C and away from light and moisture. Keep out of children’s reach.