Bicalutamide - Drug Monograph

Introduction

Bicalutamide is an oral non-steroidal antiandrogen medication primarily used in the management of prostate cancer. As a competitive antagonist at androgen receptors, it represents a cornerstone in androgen deprivation therapy for advanced prostate cancer, typically administered in combination with a gonadotropin-releasing hormone (GnRH) analog.

Mechanism of Action

Bicalutamide competitively inhibits androgen binding at cellular androgen receptors in target tissues. By blocking the action of androgens (particularly dihydrotestosterone), it prevents androgen-stimulated prostate cancer cell growth. Unlike steroidal antiandrogens, bicalutamide does not exhibit progestational activity and has minimal glucocorticoid effects. When used with GnRH analogs, it provides complete androgen blockade by inhibiting both testicular and adrenal androgen activity.

Indications

• Primary Indication: Treatment of advanced prostate cancer in combination with a GnRH analog (LHRH agonist)
• Off-label Uses: Monotherapy for locally advanced prostate cancer in selected patients, treatment of hirsutism (limited evidence)

Dosage and Administration

• Standard adult dose: 50 mg orally once daily
• Administration: Taken at the same time each day, with or without food
• Special populations:

- Renal impairment: No dosage adjustment necessary - Hepatic impairment: Use with caution in moderate to severe impairment - Elderly: No dosage adjustment required

• Duration: Continued until disease progression or unacceptable toxicity

Pharmacokinetics

• Absorption: Well absorbed orally, bioavailability not significantly affected by food
• Distribution: Highly protein-bound (96%), primarily to albumin
• Metabolism: Extensively hepatic via oxidation and glucuronidation (CYP3A4 involvement)
• Elimination: Biphasic elimination with terminal half-life of approximately 5-6 days
• Excretion: Primarily fecal (43%) and renal (34%) as metabolites

Contraindications

• Hypersensitivity to bicalutamide or any component of the formulation
• Pregnancy (FDA Pregnancy Category X)
• Women who are or may become pregnant
• Use in pediatric patients

Warnings and Precautions

• Hepatotoxicity: Rare cases of fatal hepatotoxicity reported; monitor liver function regularly
• Cardiac effects: Potential for QT interval prolongation; use caution in patients with cardiac conditions
• Glucose intolerance: May exacerbate or precipitate diabetes mellitus
• Gynecomastia and breast pain: Common side effects that may require management
• Fatigue and hot flashes: Common androgen deprivation effects
• Metabolic effects: May cause hypercholesterolemia and hypertriglyceridemia

Drug Interactions

• Warfarin: Bicalutamide may enhance anticoagulant effect; monitor INR closely
• CYP3A4 inducers: Drugs like rifampin, carbamazepine may decrease bicalutamide concentrations
• CYP3A4 inhibitors: Drugs like ketoconazole may increase bicalutamide concentrations
• Other QT-prolonging agents: Additive effects possible

Adverse Effects

• Hot flashes (49%)
• Gynecomastia (38%)
• Breast pain (39%)
• Asthenia (16%)
• Constipation (12%)
• Nausea (9%)

• Diarrhea
• Abdominal pain
• Back pain
• Pelvic pain
• Peripheral edema
• Rash
• Increased liver enzymes

• Hepatotoxicity (including hepatic failure)
• Thrombocytopenia
• Interstitial pneumonitis
• QT interval prolongation

Monitoring Parameters

• Baseline: Liver function tests, complete blood count, PSA, testosterone levels
• Ongoing:

- Liver function tests (every 3 months for first year, then periodically) - PSA levels (every 3-6 months) - Testosterone levels (periodically) - Cardiac monitoring in susceptible patients - Bone mineral density (with long-term therapy) - Lipid profile - Blood glucose monitoring

Patient Education

• Take medication exactly as prescribed at the same time each day
• Report any signs of liver problems (jaundice, dark urine, abdominal pain)
• Be aware of potential side effects including hot flashes and breast changes
• Use effective contraception as bicalutamide may harm an unborn baby
• Regular follow-up appointments are essential for monitoring
• Maintain bone health through adequate calcium/vitamin D intake and weight-bearing exercise
• Report any unusual bleeding or bruising
• Inform all healthcare providers about bicalutamide use, especially before new prescriptions

References

1. FDA Prescribing Information: Casodex (bicalutamide) 2. National Comprehensive Cancer Network (NCCN) Guidelines: Prostate Cancer Version 4.2023 3. Scher HI, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26(7):1148-1159. 4. Kolvenbag GJ, et al. Bicalutamide doses used in the treatment of prostate cancer. Prostate. 1999;39(1):47-53. 5. McLeod DG, et al. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer. BJU Int. 2006;97(2):247-254. 6. See WA, et al. Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the EPC program. J Urol. 2002;168(2):429-435. 7. American Society of Clinical Oncology (ASCO) Guidelines: Prostate Cancer