COMPOSITION
Calutide - 50
Each film-coated tablet contains Bicalutamide - 50 mg

DESCRIPTION
Bicalutamide 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.

INDICATION
Calutide- 50 is indicated in the treatment of advanced prostate cancer in combination with LHRH analogue therapy or surgical castration.

CONTRAINDICATIONS

• Bicalutamide is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any of the tablet's components.
• Calutide- 50 has no indication for women, and should not be used in this population, particularly for non-serious or non-life threatening conditions. Further, Calutide- 50 should not be used by women who are or may become pregnant. 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. Calutide- 50 may cause fetal harm when administered to pregnant women.

DOSAGE AND ADMINISTRATION
The recommended dose for bicalutamide 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 bicalutamide be taken at the same time each day. Treatment with bicalutamide should be started at the same time as treatment with an LHRH analogue.
Dosage Adjustment in Renal impairment: No dosage adjustment is necessary for patients with mild to moderate renal impairment.
Dosage Adjustment for hepatic impairment: No dosage adjustment is necessary for patients with mild-to-moderate hepatic impairment. Although there is a 76% increase in the half-life of the active enantiomer of bicalutamide in patients with severe liver impairment, no dosage adjustment is necessary.

WARNINGS AND PRECAUTIONS
General
Bicalutamide should be used with caution in patients with moderate-to-severe hepatic impairment. Bicalutamide is extensively metabolized by the liver. Limited data in subjects with severe hepatic impairment suggest that excretion of bicalutamide may be delayed and could lead to further accumulation. Serum transaminase levels should be measured prior to starting treatment with bicalutamide at regular intervals for the first four months of treatment, and periodical 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.
In clinical trials with bicalutamide as a single agent for prostate cancer, gynaecomastia and breast pain have been reported in up to 38% and 39% of patients, respectively.
Regular assessments of serum Prostate Specific Antigen (PSA) may be helpful in monitoring the patient's response. If PSA levels rise during bicalutamide 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 bicalutamide, 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, bicalutamide 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 bicalutamide can displace coumarin anticoagulants, such as warfarin, from their protein-binding sites. It is recommended that if bicalutamide is started in patients already receiving coumarin anticoagulants, prothrombin time should be closely monitored and adjustment of the anticoagulant dose may be necessary.

Pregnancy
Bicalutamide is contraindicated in pregnancy.

Pediatric use: Safety and effectiveness of bicalutamide in pediatric patients have not been established.
Side Effects: Breast tenderness or pain and gynaecomastia were the most frequent adverse events and hot flashes were also reported to occur with bicalutamide therapy. Other adverse experiences (greater than or equal to 2% but less than 5%) reported in the bicalutamide - LHRH analogue treatment group include:
Body as a whole: Neoplasm; Neck pain; Fever; Chills; Sepsis; Hernia; Cyst
Cardiovascular: Angina pectoris; Congestive heart failure; Myocardial infarct; Heart arrest; Coronary artery disorder; Syncope
Digestive: Melena; Rectal haemorrhage; Dry mouth; Dysphagia; Gastrointestinal disorder; Periodontal abscess; Gastrointestinal carcinoma
Metabolic and Nutritional: Edema; BUN increased; Creatinine increased; Dehydration; Gout; Hypercholesteremia
Musculoskeletal: Myalgia ; Leg cramps
Nervous System: Hypertonia; Confusion; Somnolence; Libido decreased; Neuropathy; Nervousness
Respiratory: Lung disorder; Asthma; Epistaxis; Sinusitis
Skin and Appendages: Dry skin; Alopecia; Pruritus; Herpes zoster; Skin carcinoma; Skin disorder
Special senses: Cataract specified
Urogenital: Dysuria; Urinary urgency; Hydronephrosis; Urinary tract disorder
Abnormal laboratory test values: Laboratory abnormalities including elevated AST, ALT, bilirubin, BUN, and creatinine and decreased hemoglobin and white cell count have been reported in both bicalutamide - LHRH analogue treated and flutamide - LHRH analogue treated patients.

OVERDOSAGE
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. Dialysis is not likely to be helpful since bicalutamide is highly protein bound and is extensively metabolized. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

PRESENTATION
Calutide-50 - Blister pack of 10's