[10] It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC).

[4][2][13] Bicalutamide was also previously used as monotherapy to treat localized prostate cancer (LPC), but authorization for this use was withdrawn following unfavorable trial findings.

[109][110] In females, due to the minimal biological importance of androgens in this sex,[111][112] the side effects of pure antiandrogens or NSAAs are few, and bicalutamide has been found to be very well tolerated.

[115] In any case, general side effects of bicalutamide that might occur in either sex include diarrhea, constipation, abdominal pain, nausea, dry skin, itching, and rash.

[127][131][132] Hundreds of additional cases of liver complications in people taking bicalutamide exist in the FDA Adverse Event Reporting System (FAERS) database.

[143][110][144][145] Relative to GnRH analogues and the steroidal antiandrogen (SAA) cyproterone acetate (CPA), bicalutamide monotherapy has a much lower incidence and severity of hot flashes and sexual dysfunction.

[109][110][104][146] In addition, unlike GnRH analogues and CPA, bicalutamide monotherapy is not associated with decreased bone mineral density or osteoporosis.

[104][110] Conversely, bicalutamide monotherapy is associated with much higher rates of breast tenderness, gynecomastia, and feminization in men than GnRH analogues and CPA.

[150][110][131][151][152][153] The drug also does not share the unique risks of diarrhea with flutamide and nausea, vomiting, visual disturbances, and alcohol intolerance with nilutamide.

[107] Bicalutamide acts as a highly selective competitive silent antagonist of the AR (IC50Tooltip half-maximal inhibitory concentration = 159–243 nM), the major biological target of the androgen sex hormones testosterone and DHTTooltip dihydrotestosterone, and hence is an antiandrogen.

[3][174][173] In addition to the classical nuclear AR, bicalutamide has been assessed at the membrane androgen receptors (mARs) and found to act as a potent antagonist of ZIP9 (IC50 = 66.3 nM), whereas it does not appear to interact with GPRC6A.

[180][172][2][181] However, typical clinical dosages of bicalutamide result in circulating levels of the drug that are thousands of times higher than those of testosterone and DHT, allowing it to powerfully prevent them from binding to and activating the receptor.

[192][193][194] As evidenced by its effectiveness in the treatment of prostate cancer and other androgen-dependent conditions, the antiandrogenic actions of bicalutamide considerably exceed any impact of the increased levels of testosterone it results in.

[50][196][197] NSAA monotherapy, including with bicalutamide, shows a number of tolerability differences from methods of androgen deprivation therapy that incorporate surgical or medical castration.

[220][221][222] As a result, bicalutamide appears to not be able to compete with testosterone in this sole part of the body to an extent sufficient to considerably interfere with androgen signaling and function.

[220][221][222] However, while bicalutamide does not seem to be able to adversely influence testicular spermatogenesis, it may interfere with AR-dependent sperm maturation and transport outside of the testes in the epididymides and vas deferens where androgen levels are far lower, and hence may still be able to impair male fertility.

[223] In addition, the combination of bicalutamide with other medications, such as estrogens, progestogens, and GnRH analogues, can compromise spermatogenesis due to their own adverse effects on male fertility.

[224][225][226][227][228][229] These medications are able to strongly suppress gonadal androgen production, which can severely impair or abolish testicular spermatogenesis, and estrogens also appear to have direct and potentially long-lasting cytotoxic effects in the testes at sufficiently high concentrations.

[232][233][234] Like other first-generation NSAAs and enzalutamide, it has been found to act as a weak non-competitive inhibitor of GABAA receptor-mediated currents in vitro (IC50 = 5.2 μM).

[235][236] However, unlike enzalutamide, bicalutamide has not been found to be associated with seizures or other related adverse central effects, so the clinical relevance of this finding is uncertain.

[271] Bicalutamide as well as all of the other currently marketed NSAAs were derived from structural modification of flutamide, which itself was originally synthesized as a bacteriostatic agent in 1967 at Schering Plough Corporation and was subsequently and serendipitously found to possess antiandrogenic activity.

[275][276][277] Bicalutamide was discovered by Tucker and colleagues at Imperial Chemical Industries (ICI) in the 1980s and was selected for development from a group of over 2,000 synthesized compounds.

[282] The pharmaceutical division of ICI was split out into an independent company called Zeneca in 1993, and in April and May 1995, Zeneca (now AstraZeneca, after merging with Astra AB in 1999) began pre-approval marketing of bicalutamide for the treatment of prostate cancer in the U.S..[283] It was first launched in the U.K.Tooltip United Kingdom in May 1995,[284] and was subsequently approved by the U.S. FDA on 4 October 1995, for the treatment of prostate cancer at a dosage of 50 mg/day in combination with a GnRH analogue.

[285][286] Following its introduction for use in combination with a GnRH analogue, bicalutamide was developed as a monotherapy at a dosage of 150 mg/day for the treatment of prostate cancer, and was approved for this indication in Europe, Canada, and a number of other countries in the late 1990s and early 2000s.

[300][80][38] Bicalutamide is marketed by AstraZeneca in oral tablet form under the brand names Casodex, Cosudex, Calutide, Calumid, and Kalumid in many countries.

[38][80][304][305] It is also marketed under the brand names Bicadex, Bical, Bicalox, Bicamide, Bicatlon, Bicusan, Binabic, Bypro, Calutol, and Ormandyl among others in various countries.

[309][310] Sales of bicalutamide (as Casodex) worldwide peaked at US$1.3 billion in 2007,[311] and it has been described as a "billion-dollar-a-year" drug prior to losing its patent protection starting in 2007.

[43][312][259] In 2014, despite the introduction of abiraterone acetate in 2011 and enzalutamide in 2012, bicalutamide was still the most commonly prescribed drug in the treatment of metastatic castration-resistant prostate cancer (mCRPC).

[332][333] Bicalutamide has been tested for the treatment of AR-positive ER/PR-negative locally advanced and metastatic breast cancer in women in a phase II study for this indication.

[344][345] Bicalutamide may be used to treat hyperandrogenism and associated benign prostatic hyperplasia secondary to hyperadrenocorticism (caused by excessive adrenal androgens) in male ferrets.