temozolomide: clinical use

Prescribing considerations

• Prescribing should be supervised by clinicians experienced in treating brain tumours.
• Assess marrow reserve, infection risk, hepatic function, pregnancy potential and fertility counselling before treatment.
• Consider antiemetic support and, where indicated by concurrent radiotherapy treatment, Pneumocystis jirovecii pneumonia prophylaxis.
• Review hepatitis B status and obtain specialist liver advice for positive serology.
• Use caution in severe hepatic impairment, renal impairment and older patients, for whom evidence or haematological tolerance may be less favourable.

Contraindications and cautions

• Hypersensitivity to temozolomide or an excipient
• Previous hypersensitivity to dacarbazine
• Severe myelosuppression

Monitoring

• Full blood count before and serially during treatment, with treatment decisions based on marrow recovery and toxicity.
• Baseline and serial liver-function tests; delayed hepatotoxicity may occur after treatment ends.
• Monitor for opportunistic infection, hepatitis B or cytomegalovirus reactivation and respiratory symptoms.
• Assess nausea, vomiting, neurological status, bleeding, infection and other non-haematological toxicity.

Clinical pharmacology

Temozolomide is an orally absorbed imidazotetrazine prodrug that undergoes non-enzymatic conversion to MTIC at physiological pH. DNA methylation, especially O6-methylguanine formation, produces cytotoxic mismatch-repair responses. It has low protein binding and penetrates the central nervous system.

Formulation and product differences

• The selected product comprises hard capsules in several strengths with colour-coded caps.
• Capsules contain lactose and are essentially sodium-free.
• Capsules are individually sealed in sachets and must not be opened or chewed.

Capsule

Route: Oral

Strengths: 5 mg, 20 mg, 100 mg, 140 mg, 180 mg, 250 mg