temsirolimus: clinical use

Prescribing considerations

• Administration must be supervised by a clinician experienced in antineoplastic therapy, with facilities for managing severe infusion reactions.
• Assess hepatic function carefully; exposure increases with hepatic impairment and licensed restrictions differ by indication.
• Consider immunosuppression, opportunistic infection risk and Pneumocystis jirovecii pneumonia prophylaxis when other immunosuppressants are required.
• Obtain baseline lung imaging and investigate new or worsening respiratory symptoms for pneumonitis and infection.
• Use caution around surgery because impaired wound healing has been reported; avoid live vaccines.

Contraindications and cautions

• Hypersensitivity to temsirolimus, its metabolites including sirolimus, polysorbate 80 or another formulation excipient.
• Mantle cell lymphoma with moderate or severe hepatic impairment.

Monitoring

• Full blood count, including neutrophils, platelets and haemoglobin
• Blood glucose and symptoms of hyperglycaemia
• Serum cholesterol and triglycerides
• Liver and renal function
• Infection, bleeding, infusion reactions and new respiratory symptoms
• Lung imaging according to clinical findings

Clinical pharmacology

Temsirolimus forms a complex with FKBP-12 that selectively inhibits mTOR and disrupts cell-cycle and angiogenic signalling. Sirolimus is its principal, similarly active metabolite. Clearance is predominantly hepatic through CYP3A metabolism; excretion is mainly faecal and renal elimination is minor.

Formulation and product differences

• The product is a sterile concentrate supplied with a separate solvent and is not ready to administer.
• The concentrate must be mixed with the supplied solvent before further dilution in sodium chloride infusion solution.
• The formulation contains ethanol and propylene glycol. The diluted product contains polysorbate 80, requiring compatible non-PVC administration materials and filtration.

Solution for infusion

Route: Intravenous

Strengths: 30 mg