BICALUTAMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BICALUTAMIDE (BICALUTAMIDE).
Bicalutamide is a non-steroidal androgen receptor antagonist that competitively inhibits the action of androgens by binding to the androgen receptor, thereby preventing androgen-mediated transactivation of target genes.
| Metabolism | Hepatic metabolism via oxidation (CYP3A4) and glucuronidation; metabolized primarily to bicalutamide glucuronide and hydroxybicalutamide; the R-enantiomer is predominantly active and cleared slowly. |
| Excretion | Approximately 10% of the dose is excreted unchanged in the urine, with 90% eliminated as metabolites via bile into feces. Less than 1% is excreted unchanged in feces. |
| Half-life | The terminal elimination half-life is approximately 5.8 days (range 4.7–7.2 days) in patients, consistent with once-daily dosing due to slow clearance. |
| Protein binding | Bicalutamide is highly protein bound (>96%), primarily to albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 13 L/kg (range 10–17 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% (complete absorption) when taken with or without food. |
| Onset of Action | Time to maximal suppression of serum prostate-specific antigen (PSA) is 1–3 months after oral administration. |
| Duration of Action | Duration of action persists for approximately 1–2 weeks after discontinuation due to long half-life; clinical effect (e.g., antiandrogen activity) is continuous with daily dosing. |
| Molecular Weight | 430.37 |
50 mg orally once daily, in combination with a gonadotropin-releasing hormone (GnRH) analog or surgical castration for the treatment of prostate cancer. For monotherapy, 150 mg orally once daily as an alternative to castration.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For moderate impairment (Child-Pugh class B), use with caution and consider dose reduction or discontinuation if liver enzymes elevate; no specific dose adjustment guidelines. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended based on age alone. Monitor for increased risk of adverse effects due to potential comorbidities and polypharmacy. |
| 1st trimester | Bicalutamide is contraindicated in pregnancy, particularly during the first trimester, due to the risk of feminization of male fetuses. It is an antiandrogen and can cause ambiguous genitalia in male offspring. Animal studies have shown teratogenic effects. Use only if clearly needed and no alternative. |
| 2nd trimester | Contraindicated. Potential for feminization of male fetus persists. No adequate human studies. Avoid use. |
| 3rd trimester | Contraindicated. Risk of feminization and other developmental anomalies. Not recommended in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for BICALUTAMIDE (BICALUTAMIDE).
| Placental transfer | Bicalutamide and its metabolites cross the placenta. Animal studies show transfer and accumulation in fetal tissues. Human data limited but likely similar. Risk of feminization of male fetuses. |
| Breastfeeding | Bicalutamide is excreted in human milk in low amounts. Due to potential for severe adverse reactions in nursing infants, including antiandrogenic effects, breast-feeding is not recommended during treatment. Alternative therapies should be considered. |
■ FDA Black Box Warning
None
| Serious Effects |
PregnancyWomen of childbearing potential (unless using effective contraception)Hypersensitivity to bicalutamide or any component of the formulationSevere hepatic impairment (Child-Pugh class C)
| Precautions | Hepatotoxicity including hepatic failure, monitor liver function tests; dose reduction or discontinuation if severe elevation of transaminases, Gynecomastia and breast pain, Decreased glucose tolerance, monitor blood glucose, Risk of thrombosis, especially in patients with underlying risk factors, Use with caution in patients with moderate to severe hepatic impairment |
| Food/Dietary | No significant food interactions. Can be taken with or without food. Avoid grapefruit juice? (No known interaction with bicalutamide). Maintain a balanced diet. Report any unusual symptoms. |
Loading safety data…
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Bicalutamide is contraindicated in pregnancy due to its antiandrogenic effects. It can cause feminization of male fetuses, including hypospadias and other genital abnormalities, particularly during first trimester sexual differentiation. Risk extends throughout gestation. |
| Fetal Monitoring | Pregnancy testing before initiation; confirm non-pregnant status. Monitor liver function tests (LFTs) and serum prostate-specific antigen (PSA) in indicated patients. Inadvertent exposure requires fetal ultrasound for genital development assessment. |
| Fertility Effects | May impair spermatogenesis and reduce fertility in males through androgen receptor blockade. In females, effects unknown. Reversible upon discontinuation. |
| Clinical Pearls | Bicalutamide is a nonsteroidal antiandrogen used in combination with a GnRH analog for advanced prostate cancer. It can cause gynecomastia and breast pain due to increased testosterone levels from LH surge. Monitor LFTs regularly, as hepatotoxicity can occur, including rare fatal cases. Discontinue if jaundice or ALT >2x ULN. It has a long half-life (5-10 days), so effects persist after discontinuation. |
| Patient Advice | Take bicalutamide once daily at the same time each day, with or without food. · It may cause hot flashes, breast swelling or tenderness, and decreased libido. · Report any signs of liver problems: yellowing of skin/eyes, dark urine, severe nausea/vomiting, or abdominal pain. · Do not stop taking this medication without consulting your doctor, as it must be used with a GnRH agonist. · Bicalutamide can cause dizziness or weakness; avoid driving until you know how it affects you. · This medication does not cure prostate cancer but helps control it. |