Casodex - Drug Monograph

Introduction

Casodex (bicalutamide) is a nonsteroidal antiandrogen medication primarily used in the treatment of prostate cancer. It belongs to the class of androgen receptor inhibitors and is commonly prescribed in combination therapy for advanced prostate cancer management.

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 testosterone-stimulated growth of prostate cancer cells. Unlike some other antiandrogens, bicalutamide does not demonstrate intrinsic agonist activity at the androgen receptor.

Indications

• Advanced prostate cancer in combination with a luteinizing hormone-releasing hormone (LHRH) analog
• Stage D2 metastatic prostate cancer (in combination therapy)
• Locally advanced prostate cancer (as part of combined androgen blockade)
• Note: Monotherapy use has declined due to inferior survival outcomes compared to combined androgen blockade

Dosage and Administration

• Hepatic impairment: Use with caution in moderate to severe impairment
• Renal impairment: No dosage adjustment typically required
• Elderly: No specific dosage adjustment recommended

Pharmacokinetics

Contraindications

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

Warnings and Precautions

• Hepatotoxicity: Cases of hepatitis and hepatic failure have been reported. Monitor liver function regularly
• Gynecomastia and breast pain: Common adverse effects that may require management
• Cardiovascular effects: May prolong QT interval; use caution in patients with cardiac history
• Glucose intolerance: May exacerbate diabetes mellitus
• Photosensitivity: Patients should avoid excessive sun exposure
• Withdrawal syndrome: Rare cases of antiandrogen withdrawal syndrome reported upon discontinuation

Drug Interactions

• Warfarin: May potentiate anticoagulant effect (monitor INR closely)
• CYP3A4 inhibitors (ketoconazole, ritonavir): May increase bicalutamide concentrations
• CYP3A4 inducers (rifampin, carbamazepine): May decrease bicalutamide concentrations
• Other highly protein-bound drugs: Potential displacement interactions

Adverse Effects

• Hot flashes (49%)
• Gynecomastia (38%)
• Breast pain (38%)
• Asthenia (15%)
• Constipation (12%)
• Nausea (11%)

• Diarrhea
• Dyspepsia
• Increased liver enzymes
• Edema
• Rash
• Pruritus
• Dry skin
• Alopecia
• Depression
• Dizziness
• Headache
• Insomnia

• Hepatotoxicity (including hepatic failure)
• QT prolongation
• Thrombocytopenia
• Interstitial lung disease
• Anaphylactic reactions

Monitoring Parameters

• Baseline: Liver function tests, complete blood count, prostate-specific antigen (PSA)
• During therapy:

- Liver function tests (regularly, especially first 4 months) - PSA levels (every 3-6 months) - Clinical symptoms of disease progression - Cardiac monitoring in patients with risk factors - Regular physical examination including breast examination

• Patient-reported symptoms: Hot flashes, gynecomastia, fatigue, gastrointestinal symptoms

Patient Education

• Take medication exactly as prescribed at the same time each day
• Report any signs of liver problems (yellowing skin/eyes, dark urine, abdominal pain)
• Be aware of potential for hot flashes and breast changes
• Use sun protection and avoid excessive sun exposure
• Inform all healthcare providers about Casodex use, especially before new prescriptions
• Do not stop medication without consulting your oncologist
• Women should not handle crushed or broken tablets if pregnant or planning pregnancy
• Regular follow-up appointments are essential for monitoring safety and efficacy

References

1. 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. 2. Schellhammer PF, et al. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for advanced prostate cancer: a report of a double-blind, randomized, multicenter trial. J Urol. 1997;158(1):21-29. 3. FDA Prescribing Information: Casodex (bicalutamide). Revised 2018. 4. Kolvenbag GJ, et al. Bicalutamide doses used in the treatment of prostate cancer. Prostate. 1999;38(4):287-293. 5. Cockshott ID. Bicalutamide: clinical pharmacokinetics and metabolism. Clin Pharmacokinet. 2004;43(13):855-878. 6. National Comprehensive Cancer Network (NCCN) Guidelines: Prostate Cancer. Version 4.2023.