cladribine: clinical use

Prescribing considerations

• Initiation and supervision require an MS specialist or clinician experienced in cancer chemotherapy, according to indication.
• Exclude or treat relevant active infections before therapy; oral cladribine requires exclusion of HIV, active tuberculosis and active hepatitis.
• Assess previous immunosuppression, marrow reserve, renal and hepatic function, pregnancy risk, vaccination status and concomitant medicines.
• For leukaemia, assess tumour burden and tumour-lysis risk. Use irradiated cellular blood components if transfusion is required.
• For oral cladribine, review previous malignancy individually and maintain standard cancer screening.

Contraindications and cautions

• Hypersensitivity to cladribine or product excipients.
• Pregnancy and breastfeeding.
• Oral cladribine: HIV infection, active tuberculosis or hepatitis, active malignancy, immunocompromised status or current immunosuppressive or myelosuppressive treatment, and moderate or severe renal impairment.
• Selected subcutaneous products: patients younger than 18 years, moderate or severe renal or hepatic impairment, and concomitant myelosuppressive medicines.
• Contraindications differ by product; do not extrapolate between tablets and injections.

Monitoring

• Full blood count with differential, with particular attention to lymphocyte recovery.
• Clinical surveillance for infection, herpes zoster and opportunistic infection; investigate unexplained fever promptly.
• Renal and hepatic function as clinically indicated; oral cladribine requires baseline liver tests and prompt repeat testing if hepatic symptoms occur.
• Pregnancy testing where relevant and review of contraception requirements.
• Baseline MRI before oral treatment to support later assessment of neurological symptoms potentially suggesting PML.
• For oncology use, monitor for tumour lysis and prolonged marrow suppression after treatment.

Clinical pharmacology

Cladribine is a chlorinated deoxyadenosine analogue and intracellularly activated prodrug. Its active triphosphate accumulates particularly in lymphocytes, inhibits ribonucleotide reductase and DNA synthesis and repair, and promotes DNA-strand breaks, energy depletion and apoptosis in dividing and resting cells.

Formulation and product differences

• Tablets are licensed for active relapsing multiple sclerosis in adults and have MS-specific infection screening, MRI, lymphocyte and liver-monitoring requirements.
• Leustat intravenous solution requires dilution and professional administration. It is licensed for hairy cell leukaemia and selected previously treated B-cell chronic lymphocytic leukaemia.
• LITAK and Leustat subcutaneous solutions are ready to use and may be self-administered after training. LITAK is licensed only for hairy cell leukaemia, while selected Leustat products also cover B-cell chronic lymphocytic leukaemia.
• Contraindications, driving cautions, handling instructions and post-treatment breastfeeding periods are formulation-specific.

Tablet

Route: Oral

Strengths: 10 mg

Injection

Route: Parenteral

Strengths: 2 mg/mL