Abiret is a CYP17 inhibitor indicated in combination with prednisone for the treatment of patients with Metastatic castration-resistant prostate cancer (CRPC). Metastatic high-risk castration-sensitive prostate cancer (CSPC).
Abiraterone Acetate is converted in vivo to Abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17, 20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions:
Recommended Dose For Metastatic CRPC : The recommended dose of Abiraterone Acetate is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with Prednisone 5 mg orally twice daily. Recommended Dose For Metastatic High-Risk CSPC : The recommended dose of Abiraterone Acetate is 1,000 mg (two 500 mg tablets or four 250 mg tablets) orally once daily with Prednisone 5 mg administered orally once daily. Patients receiving Abiraterone Acetate should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy. Abiraterone Acetate must be taken on an empty stomach, at least one hour before or at least two hours atier a meal. The tablets should be swallowed whole with water. Do not crush or chew tablets. Dose Modification : For patients with baseline moderate hepatic impairment (Child-Pugh Class B), reduce the Abiraterone Acetate starting dose to 250 mg once daily. For patients who develop hepatotoxicity during treatment, hold Abiraterone Acetate until recovery. Retreatment may be initated at a reduced dose. Abiraterone Acetate should be discontinued if patients develop severe hepatotoxicity. Avoid concomitant strong CYP3A4 inducers (e.g., Phenytoin, Carbamazepine, Rifampin, Rifabutin, Rifapentine, Phenobarbital) during Abiraterone Acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the Abiraterone Acetate dosing frequency to twice a day only during the co-administration period (e.g., from 1,000 mg once daily to 1,000 mg twice a day). Reduce the dose back to the previous dose and frequency, if the concomitant strong CYP3A4 inducer is discontinued. Or, as directed by the registered physician. Pediatric Use : The safety and effectiveness in pediatric patients have not been established.
Always consult a registered doctor before taking any medicine. This information is for general knowledge only.
The most common adverse reactions are fatigue, arthalgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough, and headache.
Hypersensitivity to the Abiraterone acetate or to any of the excipients of Abiraterone.
Drugs That Inhibit Or Induce CYP3A4 Enzymes : Based on in vitro data, Abiret is a substrate of CYP3A4. In a dedicated drug interaction trial, co-administration of Rifampin, a strong CYP3A4 inducer, decreased exposure of Abiret by 55%. Avoid concomitant strong CYP3A4 inducers during Abiret treatment. If a strong CYP3A4 inducer must be co-administered, increase the Abiret dosing frequency. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of Abiret. Effects Of Abiret On Drug Metabolizing Enzymes : Abiret is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. In a CYP2D6 drug-drug interaction trial, the Cmax and AUC of Dextromethorphan (CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively, when Dextromethorphan was given with Abiret 1,000 mg daily and Prednisone 5 mg twice daily. Avoid co-administration of Abiret with substrates of CYP2D6 with a narrow therapeutic index (e.g., Thioridazine). If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate drug. In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of Pioglitazone (CYP2C8 substrate) was increased by 46% when Pioglitazone was given together with a single dose of 1,000 mg Abiret. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with Abiret.
Abiret may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition. Patients should be monitored for hypertension, hypokalemia, and fluid retention at least once a month. Hypertension and hypokalemia should be controlled and corrected before and during treatment with Abiret. Patients should be monitored for symptoms and signs of adrenocortical insufficiency. Serum transaminases (ALT and AST) and bilirubin levels should be measured prior to starting treatment with Abiret, every two weeks for the first three months of treatment and monthly thereatier.