Bicalutamide
(British Approved Name, US Adopted Name, rINN)
Drug Nomenclature
International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):
Pharmacopoeias. In US.
The United States Pharmacopeia 31, 2008 (Bicalutamide). A fine, white to off-white powder. Sparingly to slightly soluble in alcohol; freely soluble in acetone and in tetrahydrofuran; soluble in acetonitrile. Store in airtight containers.
Adverse Effects and Precautions
As for Flutamide. Pruritus, asthenia, alopecia, hair regrowth, and dry skin occur commonly with bicalutamide. Hyper sensitivity reactions, including an-gioedema and urticaria, have been reported infrequentiyCardiovascular effects including angina, heart failure, arrhythmias, and ECG changes have been reported rarely. Interstitial pneumonitis and pulmonary fibrosis have also been reported rarely.
Effects on the gastrointestinal tract. There is some evidence that bicalutamide is associated with a lower incidence of diarrhoea than flutamide.
Effects on the lungs. For a review of cases of pneumonitis associated with anti-androgens including bicalutamide, see under Flutamide.
Gynaecomastia. For a discussion of gynaecomastia, a frequent adverse effect of anti-androgen therapy, and its management, see under Flutamide.
Interactions
Bicalutamide inhibits various cytochrome P450 isoenzymes, particularly CYP3A4, in vitro, and licensed product information recommends that terfenadine, astemizole, and cisapride should not be given with bicalutamide, and that other drugs with a narrow therapeutic index that are metabolised by cytochrome P450 isoenzymes should be used with caution. In vitro studies have shown that bicalutamide can displace warfarin from its protein binding sites (see also Antineoplastics).
Pharmacokinetics
Bicalutamide is well absorbed after oral doses. It undergoes extensive metabolism in the liver, the active R-enantiomer mainly by oxidation, the inactive S-enanti-omer mainly by glucuronidation. It is excreted as metabolites in urine and faeces. The half-life of the R-enantiomer is about 6 to 7 days, and may be prolonged still further in severe hepatic impairment. The S-enantiomer is cleared more rapidly. Bicalutamide is about 96% bound to plasma proteins.
Uses and Administration
Bicalutamide is a nonsteroidal anti-androgen with actions and uses similar to those of flutamide. It is used orally in the treatment of prostatic cancer. When used with a gonadorelin analogue in the palliative treatment of advanced prostatic cancer the usual dose is 50 mg daily. In the UK treatment is started at least 3 days before starting the gonadorelin analogue to suppress any flare reaction, but in the United States of America treatment is started at the same time. A similar dose is used with surgical castration, starting on the same day as surgery.
Bicalutamide in a dose of 150 mg daily may be given as monotherapy or adjuvant therapy to surgery or radiotherapy in men with locally advanced disease at high risk for disease progression. It has been used as mono-therapy in localised disease, but there is some evidence to suggest that in men without high risk of disease progression, who would otherwise be managed with watchful waiting, the immediate use of bicalutamide may increase the risk of death.
Preparations
Proprietary Preparations
Argentina: Androxinon †; Bicaprost; Bidrostat; Biolutam; Bitakebir; Bosconar; Casodex; Codebup; Dimalan; Finaband; Gepeprostin; Imda †; Liberprost; Raffolutil;
Australia: Cosudex;
Austria; Casodex;
Belgium: Casodex;
Brazil: Casodex; Gepeprostin; Lutamidal;
Canada: Casodex;
Chile: Casodex; Lutamidal;
Czech Republic: Bicaluplex; Calumid; Casodex; Lanbica;
Denmark: Casodex;
Finland: Casodex;
France: Casodex;
Germany; Casodex;
Greece: Bicalut; Bicamide; Casodex; Verodex;
Hong Kong; Casodex;
Hungary: Bicatlon; Bilutamid; Calumid; Casodex;
India: Caluran; Calutide;
Indonesia: Casodex;
Ireland: Casodex;
Israel: Casodex;
Italy: Casodex;
Malaysia: Casodex;
Mexico: Casodex;
The Netherlands: Casodex;
Norway: Casodex;
New Zealand: Cosudex;
Philippines: Casodex;
Poland: Casodex;
Portugal: Casodex;
Russia: Bilumid; Calumid; Casodex;
South Africa; Casodex;
Singapore: Casodex;
Spain: Casodex;
Sweden: Casodex;
Switzerland: Casodex;
Thailand: Casodex;
Turkey: Casodex;
United Kingdom (UK): Casodex;
United States of America (US and USA): Casodex;
Venezuela: Calutol; Casodex.
Multi-ingredient
Australia: Zolacos GR