Casodex 50mg Tablet

Treatment of advanced prostate cancer in combination with Luteinising Hormone Releasing Hormone (LHRH) analogue therapy or surgical castration.

Adult males including the elderly: 1 tablet (50 mg) once a day. Treatment with CASODEX should be started at least 3 days before commencing treatment with an LHRH analogue, or at the same time as surgical castration. Renal impairment: no dosage adjustment is necessary for patients with renal impairment. Hepatic impairment: no dosage adjustment is necessary for patients with mild hepatic impairment. Increased accumulation may occur in patients with moderate to severe hepatic impairment (see u201cSpecial precautionsu201d).

CASODEX is contraindicated in females and children. CASODEX must not be given to any patient who has shown a hypersensitivity reaction to the bicalutamide or to any of the excipients of CASODEX.

CASODEX is extensively metabolised in the liver. Data suggests that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of CASODEX. Therefore, CASODEX should be used with caution in patients with moderate to severe hepatic impairment. Periodic liver function testing should be considered due to the possibility of hepatic changes. Severe hepatic changes and hepatic failure have been observed rarely with CASODEX and fatal outcomes have been reported (see u201c Side Effects u201d). CASODEX therapy should be discontinued if changes are severe. A reduction in glucose tolerance has been observed in males receiving LHRH agonists and CASODEX. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes. Consideration should therefore be given to monitoring blood glucose in patients receiving CASODEX in combination with LHRH agonists. Clinically discontinuation of Casodex can result in anti-androgen withdrawal syndrome in a subset of patients. This is characterised by a decline in PSA (prostate specific antigen) or clinical response following withdrawal of the anti-androgen component of Maximal Androgen Blockade (MAB). This syndrome has been well described in scientific literature although the pathophysiology is unknown and may reflect multiple mechanisms, but is believed to represent the development of agonistic activity by the medicine at the receptor level due to receptor mutations with advancing disease. Lactose warning: The tablets contain lactose anhydrous. Patients with rare hereditary problems of galactose intolerance e.g. galactosaemia, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take CASODEX.

There is no evidence of any pharmacodynamic or pharmacokinetic interactions between CASODEX and LHRH analogues. In vitro studies have shown that (R)-CASODEX is an inhibitor of CYP 3A4, with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity. As formal interaction studies have not been undertaken, caution should be exercised when prescribing CASODEX with other medicines which may inhibit oxidation of the agent e.g. ketoconazole and cimetidine. In theory this could result in increased plasma concentrations of CASODEX, which could lead to an increase in side effects. Although clinical studies using antipyrine as a marker of cytochrome P450 (CYP) activity showed no evidence of a CASODEX interaction potential with CASODEX, the mean midazolam exposure (AUC) was increased by up to 80 %, after co-administration of CASODEX for 28 days. This rise is comparable to that seen in other studies after administration of grapefruit juice. An increase of this magnitude may be of clinical significance for medicines with a narrow therapeutic index (e.g. astemizole, cisapride and ciclosporin) such an increase could be of relevance. As such, caution should be exercised with the co-administration of CASODEX with compounds such as these. In vitro studies have shown that CASODEX can displace the coumarin anticoagulant, warfarin, from its protein binding sites. It is therefore recommended that if CASODEX is started in patients who are already receiving coumarin anticoagulants, prothrombin time should be closely monitored.

CASODEX is contraindicated in females and must not be given to pregnant women or nursing mothers.

During treatment with CASODEX, somnolence has been reported and those patients who experience this symptom should not drive or use machines.

Unless specified, the following frequency categories were assigned based on the incidence of the adverse event in the CASODEX 50 plus LHRH analogue arm of the pivotal LHRH combination study Frequency System Organ Class Adverse Event Very common ( uf0b3 10 %) Reproductive system and breast disorders Breast tenderness 1 Gynaecomastia 1 General disorders and administration site conditions Asthenia Oedema Nervous system disorders Dizziness Vascular disorders Hot flush Blood and lymphatic Anaemia Gastrointestinal disorders Abdominal pain Nausea Constipation Frequency System Organ Class Adverse Event Common ( uf0b3 1 % and < 10 %) Gastrointestinal disorders Dyspepsia Flatulence Metabolism and nutrition disorders Decreased appetite Psychiatric disorders Decreased libido Depression Common ( uf0b3 1 % and < 10 %) Reproductive system and breast disorders Erectile dysfunction Nervous system Disorders Somnolence Skin and subcutaneous tissue disorders Alopecia Dry skin Hirsutism/hair re-growth Rash Pruritus Hepatobiliary disorders Hepatotoxicity, jaundice, hypertransaminasaemia 2 General disorders and administration site condition Chest pain Investigations Weight increased Cardiac disorders Myocardial infarction (fatal outcomes have been reported) Cardiac failure Uncommon ( uf0b3 0,1 % and < 1 %) Immune system disorders Hypersensitivity, angioedema and urticaria 1 May be reduced by concomitant castration. 2 Hepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following cessation of therapy.

There is no human experience of overdosage. There is no specific antidote; treatment should be symptomatic. Dialysis may not be helpful, since CASODEX is highly protein bound and is not recovered unchanged in the urine. General supportive care, including frequent monitoring of vital signs, is indicated.