Abiraterone Acetate is a CYP17 inhibitor that is used in conjunction with prednisone to treat patients with
- Castration-resistant prostate cancer with metastasis (CRPC).
- Castration-sensitive prostate cancer with metastasis (CSPC).
Abiraterone is an orally active steroidal enzyme inhibitor of CYP17A1 (17 alpha-hydroxylase/C17,20 lyase). Through a covalent binding mechanism, it inhibits CYP17A1 in a selective and irreversible manner. CYP17A1 is an enzyme that catalyzes androgen biosynthesis and is found in high concentrations in testicular, adrenal, and prostatic tumor tissue. More specifically, abiraterone inhibits the enzyme CYP17A1’s conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), lowering serum levels of testosterone and other androgens.
Dosage & Administration
Abemaciclib tablets are taken orally with or without food.
- In combination with fulvestrant, tamoxifen, or an aromatase inhibitor, the recommended starting dose is 150 mg twice daily.
- Recommended starting dose as monotherapy: 200 mg twice daily.
- Dosing interruption and/or dose reductions may be required based on individual safety and tolerability.
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.
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.
Protein kinase inhibitor
Keep below 30°C and away from light and moisture. Keep out of children’s reach.