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Conventional DMARD — Alkylating Agent Pregnancy: D — avoid; teratogenic. Effective contraception required during and for 6 months after treatment

Cyclophosphamide (Rheumatology)

Brand names: Endoxana

Adult dose

Dose: 500–750 mg/m² IV pulse monthly (ANCA vasculitis); 1–2 mg/kg/day orally (diffuse proliferative lupus nephritis)
Route: Intravenous or Oral
Frequency: Monthly IV pulse (EUVAS protocol) or daily oral
Max: Cumulative IV lifetime dose: monitor — bladder cancer risk increases significantly above 25 g
Always co-prescribe MESNA (uroprotection) with IV cyclophosphamide — ratio 20% of cyclophosphamide dose at 0, 4, 8 hours. Maintain urine output >100 mL/h during infusion.

Paediatric dose

Dose: 500–750 mg/m²/kg
Route: Intravenous
Frequency: Monthly (up to 6 pulses)
Max: 750 mg/m² per pulse
Paediatric ANCA vasculitis — under specialist oncology/rheumatology guidance only

Dose adjustments

Renal

Reduce dose if eGFR <20 mL/min; consider 25% dose reduction

Hepatic

Use with caution; cyclophosphamide requires hepatic activation — impaired activation with severe hepatic disease

Paediatric weight-based calculator

Paediatric ANCA vasculitis — under specialist oncology/rheumatology guidance only

Clinical pearls

  • EUVAS CYCLOPS trial: IV pulse cyclophosphamide equivalent to oral for ANCA vasculitis remission with lower cumulative dose and fewer side effects — IV pulse is now preferred
  • Euro-Lupus regimen: low-dose IV cyclophosphamide (6 × 500 mg pulses fortnightly) non-inferior to high-dose NIH regimen for European lupus nephritis populations
  • MESNA uroprotection is MANDATORY with IV use; haemorrhagic cystitis is prevented but not always avoidable without it
  • Fertility preservation: sperm cryopreservation / oocyte banking must be discussed before starting — premature ovarian failure risk is age-dependent and cumulative dose-dependent
  • Cumulative lifetime dose: bladder cancer risk begins to rise significantly above 25 g total IV — track cumulative dose

Contraindications

  • Urinary outflow obstruction
  • Haemorrhagic cystitis
  • Severely immunocompromised
  • Active infection
  • Pregnancy

Side effects

  • Haemorrhagic cystitis — prevented by MESNA and adequate hydration
  • Myelosuppression — nadir day 10–14
  • Premature ovarian failure / infertility — discuss fertility preservation before initiation
  • Bladder transitional cell carcinoma (long-term)
  • Opportunistic infections
  • Nausea and vomiting
  • Alopecia (temporary)

Interactions

  • Allopurinol — increases myelosuppression; avoid or reduce cyclophosphamide dose
  • Warfarin — variable effect; monitor INR closely
  • Succinylcholine — cyclophosphamide inhibits pseudocholinesterase; prolonged neuromuscular blockade

Monitoring

  • FBC (including WBC nadir at day 10–14 after each pulse)
  • Urinalysis — haematuria
  • Serum creatinine
  • Fertility counselling documentation before starting
  • Annual urine cytology if cumulative dose >25 g

Reference: BNFc; BNF 90; CYCLOPS Trial (NEJM 2009); Euro-Lupus Nephritis Trial (Lancet 2002); EUVAS Guidelines; BSR/BHPR ANCA Vasculitis Guidelines. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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