Abiraterone acetate

Abiraterone acetate, sold under the brand name Zytiga among others, is an antiandrogen medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration and prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) and in the treatment of metastatic high-risk castration-sensitive prostate cancer (mCSPC). It is taken by mouth once per day on an empty stomach. Another formulation is Yonsa, which can be taken with or without food, at a lower dose. Abiraterone acetate, sold under the brand name Zytiga among others, is an antiandrogen medication which is used in the treatment of prostate cancer. It is specifically indicated for use in conjunction with castration and prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) and in the treatment of metastatic high-risk castration-sensitive prostate cancer (mCSPC). It is taken by mouth once per day on an empty stomach. Another formulation is Yonsa, which can be taken with or without food, at a lower dose. Side effects of abiraterone acetate include fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flashes, diarrhea, vomiting, cough, headache, glucocorticoid deficiency, mineralocorticoid excess, and hepatotoxicity among others. The drug is an androgen synthesis inhibitor – specifically, a CYP17A1 inhibitor – and thereby inhibits the production of androgens like testosterone and dihydrotestosterone in the body. In doing so, it prevents the effects of these hormones in the prostate gland and elsewhere in the body. Abiraterone acetate is a prodrug of abiraterone. Abiraterone acetate was first described in 1993 and was introduced for medical use in 2011. It was approved for the treatment of mCRPC in 2011 and was subsequently approved for the treatment of mCSPC in 2018. The medication is marketed widely throughout the world. It is available as a generic medication from Apotex Corp, at about the same cost. Abiraterone acetate is indicated for use in combination with prednisone, a corticosteroid, as a treatment for mCRPC (previously called hormone-resistant or hormone-refractory prostate cancer). This is a form of prostate cancer that is not responding to first-line androgen deprivation therapy or treatment with androgen receptor antagonists. Abiraterone acetate has received FDA (28 April 2011), EMA (23 September 2011), MHRA (5 September 2011) and TGA (1 March 2012) approval for this indication. In Australia it is covered by the Pharmaceutical Benefits Scheme when being used to treat castration-resistant prostate cancer and given in combination with prednisone/prednisolone (subject to the conditions that the patient is not currently receiving chemotherapy, is either resistant or intolerant of docetaxel, has a WHO performance status of <2, and his disease has not since become progressive since treatment with PBS-subsidised abiraterone acetate has commenced). Abiraterone may be useful for prevention of the testosterone flare at the initiation of GnRH agonist therapy in men with prostate cancer. A phase III study in subjects previously treated with docetaxel started in 2008. In September 2010, an independent panel found that the interim results in patients previously treated with docetaxel were so much better compared to those treated with placebo that it was unethical to keep half the study participants on placebo, and all patients began receiving the drug. Overall survival was increased by 3.9 months in to this study (14.8 months versus 10.9 months for placebo). A placebo-controlled double-blind randomized phase III study in patients with castration-refractory prostate cancer but who had not received chemotherapy opened to accrual in April 2009. 1,088 men received either abiraterone acetate (1000 mg daily) plus prednisone (5 mg twice daily), or placebo plus prednisone. The median radiographic progression-free survival was 16.5 months with abiraterone acetate–prednisone and 8.3 months with prednisone alone (hazard ratio (HR) = 0.53; 95% confidence interval (CI), 0.45 to 0.62; P<0.001). After a median follow-up period of 22.2 months, overall survival was better with abiraterone acetate plus prednisone (median not reached) compared to placebo plus prednisone (27.2 months); HR = 0.75; 95% CI, 0.61 to 0.93; P=0.01). Abiraterone acetate is available in the form of 250 mg and 500 mg film-coated oral tablets and 250 mg uncoated oral tablets. It is used at a dosage of 1,000 mg orally once per day an empty stomach, in conjunction with castration (via GnRH analogue therapy or orchiectomy) and in combination with 5 mg prednisone orally twice per day. Contraindications include hypersensitivity to abiraterone acetate. Although documents state that it should not be taken by women who are or who may become pregnant, there is no medical reason that any woman should take it. Women who are pregnant should not even touch the pills unless they are wearing gloves. Other cautions include severe baseline hepatic impairment, mineralocorticoid excess, cardiovascular disease including heart failure and hypertension, uncorrected hypokalemia, and adrenocorticoid insufficiency.