ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
Multiple Sclerosis — Disease-Modifying Therapy Pregnancy: Absolutely contraindicated — embryotoxic and teratogenic; mandatory contraception during and for 6 months after each treatment course in both sexes

Cladribine

Brand names: Mavenclad

Adult dose

Dose: 3.5 mg/kg total dose over 2 years — given as 2 treatment weeks per year (1.75 mg/kg per year); daily dose based on weight (range 10–20 mg/day for 4–5 days per treatment week)
Route: Oral
Frequency: Two short annual courses (year 1 and year 2); no treatment in years 3–4
Max: 20 mg/day per treatment day
Take on an empty stomach. Wash hands after handling tablets. Do not open or crush. Treatment-free years 3 and 4 — monitor for ongoing treatment effect. Highly effective but teratogenic — mandatory contraception.

Paediatric dose

Dose: Seek specialist opinion N/A/kg
Route: Oral
Frequency: N/A
Max: N/A
Not licensed under 18; seek specialist paediatric neurology opinion

Dose adjustments

Renal

Avoid in moderate-severe renal impairment (eGFR below 60) — cladribine is primarily renally excreted and lymphopenia risk is increased

Hepatic

Avoid in moderate-severe hepatic impairment — limited data

Paediatric weight-based calculator

Not licensed under 18; seek specialist paediatric neurology opinion

Clinical pearls

  • Mechanism: prodrug adenosine deaminase inhibitor — converted intracellularly to cladribine triphosphate in lymphocytes; accumulates preferentially in lymphocytes (high deoxycytidine kinase/cytosolic 5-nucleotidase ratio); causes lymphocyte DNA strand breaks and apoptosis; selective and prolonged lymphocyte depletion
  • CLARITY trial (NEJM 2010): cladribine tablets vs placebo in RRMS — 58% relative reduction in annualised relapse rate; 33% relative reduction in 3-month sustained disability progression
  • UNIQUE dosing: 2-year pulsed therapy then TREATMENT-FREE YEARS 3 and 4 — potential for treatment-free remission; total treatment time approximately 10 days across 2 years; maximum oral convenience for highly effective therapy
  • MHRA 2017: licensed for highly active RRMS — defined as one relapse in previous year on prior therapy, or 2+ relapses in previous year regardless of therapy; not licensed for PPMS
  • LYMPHOCYTE MONITORING: Grade 3 lymphopenia (0.5–0.2 × 10⁹/L) — do not start next treatment course; Grade 4 (below 0.2) — no additional treatment courses until recovery; anti-infective prophylaxis (aciclovir) mandatory during grade 3/4
  • MHRA PREGNANCY: absolutely contraindicated; male and female patients must use effective contraception during and for 6 months after last dose of each yearly course

Contraindications

  • HIV infection or other severe immunodeficiency
  • Active malignancy
  • Active tuberculosis or severe active infections
  • Moderate-severe renal impairment (eGFR below 60)
  • Pregnancy or inadequate contraception
  • Hepatitis B or C (relative — specialist assessment required)

Side effects

  • Lymphopenia (expected — grade 3/4 lymphopenia in 25%: below 0.5 × 10⁹/L; monitor closely)
  • Herpes zoster reactivation (increased risk during lymphopenia phase)
  • Malignancy risk (historical concern — haematological malignancies; CLARITY extension showed no significant increase vs placebo)
  • Nausea, headache
  • Alopecia
  • Infertility risk (male and female — temporary)

Interactions

  • Myelosuppressive agents (additive haematological toxicity — avoid)
  • Immunosuppressants (additive — avoid concurrent use)
  • Live vaccines (contraindicated during lymphopenia phase)

Monitoring

  • Lymphocyte count (at months 2 and 6 of each treatment year, and before each course)
  • FBC at baseline and regularly
  • Hepatitis B/C and HIV serology before starting
  • VZV IgG — vaccinate if seronegative before starting (wait 4–6 weeks before first dose)
  • MRI brain (annual disease activity monitoring)
  • Pregnancy test before each treatment course (mandatory)

Reference: BNFc; BNF 90; CLARITY trial NEJM 2010;362(5):416-426; NICE TA616; MHRA 2017; ESC MS Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Drugs
Pathways