It is a CYP17 inhibitor indicated for use in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.
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:
1. The conversion of pregnenolone and progesterone to their 17 α-hydroxy derivatives by 17 α-hydroxylase activity and
2. The subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by Abiraterone can also result in increased mineralocorticoid production by the adrenals. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor.
Abiraterone Acetate decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of Abiraterone Acetate on serum testosterone levels. Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients.
Recommended dose: It 1,000 mg administered orally once daily in combination with prednisone 5 mg administered orally twice daily. It must be taken on an empty stomach. No food should be consumed for at least two hours before the dose of It is taken and for at least one hour after the dose of It is taken. ? For patients with baseline moderate hepatic impairment (Child-Pugh Class B),reduce the It starting dose to 250 mg once daily. ? For patients who develop hepatotoxicity during treatment,hold It until recovery. Retreatment may be initiated at a reduced dose. It should be discontinued if patients develop severe hepatotoxicity.
Drugs That Inhibit Or Induce CYP3A4 Enzymes: Based on in vitro data, Abiraterone Acetate is a substrate of CYP3A4. In a dedicated drug interaction trial, co-administration of Rifampin, a strong CYP3A4 inducer, decreased exposure of Abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during Abiraterone Acetate treatment. If a strong CYP3A4 inducer must be co-administered, increase the Abiraterone Acetate 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 Abiraterone.
Effects Of Abiraterone On Drug Metabolizing Enzymes: Abiraterone Acetate 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 Abiraterone Acetate 1,000 mg daily and Prednisone 5 mg twice daily. Avoid co-administration of Abiraterone Acetate 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 Abiraterone Acetate. Therefore, patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with Abiraterone Acetate.
It is contraindicated in women who are or may become pregnant.
Joint swelling or discomfort, hypokalemia,edema,muscle discomfort,hot flush,diarrhea,urinary tract infection,cough,hypertension,arrhythmia,urinary frequency,nocturia, dyspepsia,and upper respiratory tract infection
There are no human data on the use of Abiraterone in pregnancy and it is not for use in women of childbearing potential. Maternal use of a CYP17 inhibitor is expected to produce changes in hormone levels that could affect development of the foetus. Pregnancy: Abiraterone is not for use in women. Abiraterone acetate is contraindicated in women who are or may potentially by pregnant. Breast feeding: Abiraterone is not for use in women. It is not known if either abiraterone acetate or its metabolites are excreted in human milk
There is no specific antidote. In the event of an overdose, Abiraterone Acetate should be stopped, general supportive measures are undertaken, including monitoring for arrhythmias and cardiac failure and assess liver function.
Do not store above 25°C. Protect from light. Keep out of the reach of children.
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