Bicalutamide

Bicalutamide tablets, USP 50 mg daily are indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analog for the treatment of Stage D 2 metastatic carcinoma of the prostate. Bicalutamide tablets, USP 150 mg daily are not approved for use alone or with other treatments [see Clinical Studies (14.2)]. • Bicalutamide tablet 50 mg is an androgen receptor inhibitor indicated for use in combination therapy with a luteinizing hormone-releasing hormone (LHRH) analog for the treatment of Stage D 2 metastatic carcinoma of the prostate. (1) • Bicalutamide tablet 150 mg daily is not approved for use alone or with other treatments. (1)

• The recommended dose for bicalutamide tablets therapy in combination with an LHRH analog is one 50 mg tablet once daily (morning or evening)
• Recommended Dose and Schedule The recommended dose for bicalutamide tablets 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 tablets should be started at the same time as treatment with an LHRH analog
• If a dose of bicalutamide tablets is missed, take the next dose at the scheduled time
• Do not take the missed dose and do not double the next dose
• Dosage Adjustment in Renal Impairment No dosage adjustment is necessary for patients with renal impairment [see Use in Specific Populations ]
• Dosage Adjustment in Hepatic Impairment 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 ]

Bicalutamide 50 mg tablets for oral administration. 50 mg tablets (3)

• The safety and effectiveness of bicalutamide
• In pediatric patients have not been established
• Bicalutamide orodispersible tablet was studied in combination with Arimidex # (anastrozole) orodispersible tablet in an open-label, non-comparative, multi-center study that assessed the efficacy and safety of this combination regimen over 12 months in the treatment of gonadotropin-independent precocious puberty in boys with familial male-limited precocious puberty, also known as testotoxicosis. …

In two studies in patients given 50 mg or 150 mg daily, no significant relationship between age and steady-state levels of total bicalutamide or the active R-enantiomer has been shown.

• Advise the patient to read the FDA-approved patient labeling (Patient Information)
• Dose and Schedule: Inform patients that therapy with bicalutamide and the LHRH analog should be started at the same time and that they should not interrupt or stop taking these medications without consulting their healthcare provider [see Dosage and Administration ]
• Hepatitis: Inform patients that bicalutamide can cause hepatitis, which may result in hepatic failure and death
• Advise patients that liver function tests should be monitored regularly during treatment and to report signs and symptoms of hepatitis [see Warnings and Precautions ]. …

• Bicalutamide is contraindicated in: • Hypersensitivity Bicalutamide is 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. • Women Bicalutamide has no indication for women, and should not be used in this population. • Pregnancy Bicalutamide can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ]. …

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. …

• 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. ( 5.1 ) • 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. ( 5.2 ) • Gynecomastia and breast pain have been reported during treatment with bicalutamide 150 mg when used as a single agent. …

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. Adverse reactions that occurred in more than 10% of patients receiving bicalutamide plus an LHRH-A were: hot flashes, pain (including general, back, pelvic and abdominal), asthenia, constipation, infection, nausea, peripheral edema, dyspnea, diarrhea, hematuria, nocturia, and anemia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. …

8.1 Pregnancy Risk Summary Bicalutamide is contraindicated for use in pregnant women because it can cause fetal harm. Bicalutamide is not indicated for use in females. There are no human data on the use of bicalutamide in pregnant women. …

Long-term clinical trials have been conducted with dosages up to 200 mg of bicalutamide daily and these dosages have been well tolerated. A single dose of bicalutamide that results in symptoms of an overdose considered to be life threatening has not been established. There is no specific antidote; treatment of an overdose should be symptomatic. In the management of an overdose with bicalutamide, vomiting may be induced if the patient is alert. It should be remembered that, in this patient population, multiple drugs may have been taken. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.