Bicalutamide Tablet, Film Coated

Bicalutamide 50 mg daily is indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analog for the treatment of Stage D₂ metastatic carcinoma of the prostate.

Bicalutamide 150 mg daily is not approved for use alone or with other treatments [see Clinical Studies (14.2)].

• Hypersensitivity (4.1)

• Women (4.2)

• Pregnancy (4.3 and 8.1) 4.1 Hypersensitivity

Bicalutamide tablets are contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any of the tablet’s components. Hypersensitivity reactions including angioneurotic edema and urticaria have been reported [

see Adverse Reactions (6.2)

]. 4.2 Women

Bicalutamide tablets have no indication for women, and should not be used in this population. 4.3 Pregnancy

Bicalutamide tablets may cause fetal harm when administered to a pregnant woman. Bicalutamide tablets are contraindicated in women, including those who are or may become pregnant. There are no studies in pregnant women using bicalutamide. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be appraised of the potential hazard to the fetus [

see Use in Specific Populations (8.1)

].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Rare cases of death or hospitalization due to severe liver injury have been reported postmarketing in association with the use of bicalutamide. Hepatotoxicity in these reports generally occurred within the first three to four months of treatment. Hepatitis or marked increases in liver enzymes leading to drug discontinuation occurred in approximately 1% of bicalutamide patients in controlled clinical trials.

Serum transaminase levels should be measured prior to starting treatment with bicalutamide, at regular intervals for the first four months of treatment, and periodically thereafter. If clinical symptoms or signs suggestive of liver dysfunction occur (e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, “flu-like” symptoms, dark urine, jaundice, or right upper quadrant tenderness), the serum transaminases, in particular the serum ALT, should be measured immediately. If at any time a patient has jaundice, or their ALT rises above two times the upper limit of normal, bicalutamide should be immediately discontinued with close follow-up of liver function.

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

No dosage adjustment is necessary for patients with renal impairment [see Use in Specific Populations (8.7)].

No dosage adjustment is necessary for patients with mild to moderate hepatic impairment. In patients with severe liver impairment (n = 4), although there was a 76% increase in the half-life (5.9 and 10.4 days for normal and impaired patients, respectively) of the active enantiomer of bicalutamide no dosage adjustment is necessary [see Use in Specific Populations (8.6)].

Bicalutamide tablets, 50 mg for oral administration.

Clinical studies have not shown any drug interactions between bicalutamide and LHRH analogs (goserelin or leuprolide). There is no evidence that bicalutamide induces hepatic enzymes.

In vitro studies have shown that R-bicalutamide is an inhibitor of CYP 3A4 with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity. Clinical studies have shown that with coadministration of bicalutamide, mean midazolam (a CYP 3A4 substrate) levels may be increased 1.5 fold (for C_max) and 1.9 fold (for AUC). Hence, caution should be exercised when bicalutamide is coadministered with CYP 3A4 substrates.

In vitro protein-binding studies have shown that bicalutamide can displace coumarin anticoagulants from binding sites. Prothrombin times should be closely monitored in patients already receiving coumarin anticoagulants who are started on bicalutamide and adjustment of the anticoagulant dose may be necessary.