Bicalutamide - Warnings and Precautions

WARNINGS AND PRECAUTIONS Severe hepatic injury and fatal hepatic failure have been observed.

Monitor serum transaminase levels prior to starting treatment with bicalutamide, at regular intervals for the first four months of treatment and periodically thereafter, and for symptoms or signs suggestive of hepatic dysfunction.

Use bicalutamide with caution in patients with hepatic impairment.

Hemorrhage with Concomitant Use of Coumarin Anticoagulant.

Closely monitor the Prothrombin Time (PT) and International Normalized Ratio (INR), and adjust the anticoagulant dose as needed.

Gynecomastia and breast pain have been reported during treatment with bicalutamide 150 mg when used as a single agent.

Bicalutamide is used in combination with an LHRH agonist.

LHRH agonists have been shown to cause a reduction in glucose tolerance in males.

Consideration should be given to monitoring blood glucose in patients receiving bicalutamide in combination with LHRH agonists.

Monitoring Prostate Specific Antigen (PSA) is recommended.

Evaluate for clinical progression if PSA increases.

Hepatitis Cases of death or hospitalization due to severe liver injury (hepatic failure) have been reported postmarketing in association with the use of bicalutamide tablets.

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 tablet patients in controlled clinical trials.

Serum transaminase levels should be measured prior to starting treatment with bicalutamide tablets, 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 tablets should be immediately discontinued with close follow-up of liver function.

Hemorrhage with Concomitant Use of Coumarin Anticoagulant In the postmarketing setting, there have been reports of excessive prolongation of the prothrombin time (PT) and International Normalized Ratio (INR) days to weeks after the introduction of bicalutamide in patients who were previously stable on coumarin anticoagulants.

Some patients had serious bleeding including intracranial, retroperitoneal, and gastrointestinal requiring blood transfusion and/or administration of vitamin K.

Closely monitor the PT/INR, and adjust the anticoagulant dose as needed [see Drug Interactions and Adverse Reactions ].

Gynecomastia and Breast Pain In clinical trials with bicalutamide 150 mg as a single agent for prostate cancer, gynecomastia and breast pain have been reported in up to 38% and 39% of patients, respectively.

Glucose Tolerance A reduction in glucose tolerance has been observed in males receiving LHRH agonists.

This may manifest as diabetes or loss of glycemic control in those with pre-existing diabetes.

Consideration should therefore be given to monitoring blood glucose in patients receiving bicalutamide in combination with LHRH agonists.

Laboratory Tests Regular assessments of serum Prostate Specific Antigen (PSA) may be helpful in monitoring the patient’s response.