Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Adult Dosage

Adult males including the elderly: one 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

Child Dosage

Contra Indications

Casodex is contraindicated in females and children.

Casodex must not be given to any patient who has shown a hypersensitivity reaction to its use.

Co-administration of terfenadine, astemizole or cisapride with Casodex is contraindicated.

Special Precautions

Initiation of treatment should be under the direct supervision of a specialist.

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. The majority of changes are expected to occur within the first 6 months of Casodex therapy.

Severe hepatic changes and hepatic failure have been observed rarely with Casodex. Casodex therapy should be discontinued if changes are severe.

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

Casodex has been shown to inhibit cytochrome P450 (CYP 3A4), as such caution should be exercised when co-administered with drugs metabolised predominantly by CYP 3A4.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Interactions

There is no evidence of any pharmacodynamic or pharmacokinetic interactions between Casodex and LHRH analogues.

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.

Although clinical studies using antipyrine as a marker of cytochrome P450 (CYP) activity showed no evidence of a drug interaction potential with Casodex, mean midazolam exposure (AUC) was increased by up to 80%, after co-administration of Casodex for 28 days. For drugs with a narrow therapeutic index such an increase could be of relevance. As such, concomitant use of terfenadine, astemizole and cisapride is contraindicated (see section 4.3) and caution should be exercised with the co-administration of Casodex with compounds such as ciclosporin and calcium channel blockers. Dosage reduction may be required for these drugs particularly if there is evidence of enhanced or adverse drug effect. For ciclosporin, it is recommended that plasma concentrations and clinical condition are closely monitored following initiation or cessation of Casodex therapy.

Caution should be exercised when prescribing Casodex with other drugs which may inhibit drug oxidation e.g. cimetidine and ketoconazole. In theory, this could result in increased plasma concentrations of Casodex which theoretically could lead to an increase in side effects.

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.

Adverse Reactions

In this section, undesirable effects are defined as follows: Very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to 1/100); rare (1/10,000 to 1/1,000); very rare (1/10,000); not known (cannot be estimated from the available data).

Table 1 Frequency of Adverse Reactions

1. Hepatic changes are rarely severe and were frequently transient, resolving or improving with continued therapy or following cessation of therapy.

2. Hepatic failure has occurred rarely in patients treated with Casodex, but a causal relationship has not been established with certainty. Periodic liver function testing should be considered.

3. May be reduced by concomitant castration.

In addition, cardiac failure was reported in clinical trials (as a possible adverse drug reaction in the opinion of investigating clinicians, with a frequency of > 1%) during treatment with Casodex plus an LHRH analogue. There is no evidence of a causal relationship with drug treatment. 

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