PDR® entry for 
CASODEX (ZENECA PHARMACEUTICALS)ESCRIPTION: 
CASODEX® (bicalutamide) Tablets for oral administration contain 50 mg of bicalutamide, a non-steroidal antiandrogen with no other known endocrine activity. 

MECHANISM OF ACTION: CASODEX is a non-steroidal antiandrogen. It competitively inhibits the action of androgens by binding to cytosol androgen receptors in the target tissue. Prostatic carcinoma is known to be androgen sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen. 

In clinical trials with CASODEX as a single agent for prostate cancer, rises in serum testosterone and estradiol have been noted. When CASODEX is combined with luteinizing hormone-releasing hormone (LHRH) analogue therapy, CASODEX does not affect the suppression of serum testosterone induced by the LHRH analogue. 
 

CLINICAL STUDIES:

In a large multicenter, double-blind, controlled clinical trial, 813 patients with previously untreated advanced prostate cancer were randomized to receive CASODEX 50 mg once daily (404 patients) or flutamide 250 mg (409 patients) three times a day, each in combination with LHRH analogues (either goserelin acetate implant or leuprolide acetate depot). At a median follow-up of 95 weeks, time to treatment failure with CASODEX-LHRH analogue therapy was not dissimilar when compared to flutamide-LHRH analogue therapy. 

At the same timepoint, 130 (32%) patients treated with CASODEX-LHRH analogue therapy and 145 (35%) patients treated with flutamide-LHRH analogue therapy had died. 
 

INDICATIONS AND USAGE:

CASODEX is indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analogue for the treatment of Stage D2 metastatic carcinoma of the prostate. 

CONTRAINDICATIONS:

CASODEX is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any of the tablet's components. 
 
 WARNINGS: 
In clinical trials with CASODEX as a single agent for prostate cancer, gynecomastia and breast pain have been reported in up to 38% and 39% of patients, respectively. 

PRECAUTIONS:

CASODEX should be used with caution in patients with moderate-to-severe hepatic impairment. CASODEX is extensively metabolized by the liver. Limited data in subjects with severe hepatic impairment suggest that excretion of CASODEX may be delayed and could lead to further accumulation. Periodic liver function tests should be considered for patients on long-term therapy. 

INFORMATION FOR PATIENTS: Patients should be informed that therapy with CASODEX and the LHRH analogue should be initiated concomitantly, and that they should not interrupt or stop taking these medications without consulting their physician. Treatment with CASODEX should be started at the same time as treatment with an LHRH analogue. 

LABORATORY TESTS: Regular assessments of serum Prostate Specific Antigen (PSA) may be helpful in monitoring the patient's response. If PSA levels rise during CASODEX therapy, the patient should be evaluated for clinical progression. For patients who have objective progression of disease together with an elevated PSA, a treatment-free period of antiandrogen, while continuing the LHRH analogue, may be considered. 

Since transaminase abnormalities and, rarely, jaundice have been reported with the use of CASODEX, periodic liver function tests should be considered. If clinically indicated, eg, when the patient has jaundice or laboratory evidence of liver injury in the absence of liver metastases, CASODEX therapy should be discontinued. If transaminases increase over 2 times the upper limit of normal, treatment should be discontinued. Abnormalities are usually reversible upon discontinuation. 

DRUG INTERACTIONS: In Vitro studies have shown CASODEX can displace coumarin anticoagulants, such as warfarin, from their protein-binding sites. It is recommended that if CASODEX is started in patients already receiving coumarin anticoagulants, prothrombin times should be closely monitored and adjustment of the anticoagulant dose may be necessary (see ACTIONS/CLINICAL PHARMACOLOGY, Drug-Drug Interactions). 
 
 

ADVERSE REACTIONS:

In patients with advanced prostate cancer treated with CASODEX in combination with an LHRH analogue, the most frequent adverse experience was hot flashes (49%). 

Diarrhea was the adverse event most frequently leading to treatment withdrawal: 6% of the patients treated with flutamide-LHRH analogue and 0.5% of the patients treated with CASODEX-LHRH analogue. 
 

DOSAGE AND ADMINISTRATION:

The recommended dose for CASODEX therapy in combination with an LHRH analogue is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that CASODEX be taken at the same time each day. Treatment with CASODEX should be started at the same time as treatment with an LHRH analogue. 
 
 HOW SUPPLIED: 
50 MG TABLET. 

Store at controlled room temperature, 20 deg-25° C (68 deg-77° F).