ANCA Vasculitis / Lupus Nephritis Pregnancy: Contraindicated — teratogenic. Effective contraception during and for at least 6 months after treatment.

Cyclophosphamide (Nephrology)

Brand names: Endoxana

Adult dose

Dose: Pulse IV: 500-750 mg/m2 every 3-4 weeks x6 cycles (EUVAS regime). Oral: 2 mg/kg/day up to 3 months.

Route: IV infusion or Oral

Frequency: Per protocol

Max: Minimise cumulative dose — bladder toxicity increases above 36 g cumulative

IV pulse preferred over oral (CYCLOPS trial — equivalent efficacy, less bladder/infection toxicity). Always give mesna with IV pulse to prevent haemorrhagic cystitis. PCP prophylaxis mandatory (co-trimoxazole 480 mg OD or 960 mg three times weekly).

Paediatric dose

Dose: 500-750 mg/m2/kg

Route: IV infusion

Frequency: Every 4 weeks for 6 cycles

Max: Per protocol

Specialist only. Mesna and PCP prophylaxis apply in children.

Dose adjustments

Renal

Reduce dose for eGFR <30 (active metabolites accumulate). Consider 25-50% dose reduction with close haematological monitoring.

Hepatic

Reduce dose in severe hepatic impairment (reduced prodrug activation)

Paediatric weight-based calculator

Patient weight (kg)

Specialist only. Mesna and PCP prophylaxis apply in children.

Clinical pearls

CYCLOPS trial (de Groot et al. Ann Intern Med 2009): pulse IV vs oral cyclophosphamide in ANCA vasculitis — equivalent remission rates; pulse route had lower cumulative dose and less leukopenia. Pulse IV now preferred.
Euro-Lupus Nephritis Trial (Houssiau et al. 2002): low-dose IV pulse cyclophosphamide (500 mg x6 fortnightly) non-inferior to high-dose in lupus nephritis — lower toxicity. Low-dose regime now standard in Europe.
Fertility preservation: counsel ALL patients before starting. Men — sperm banking. Women — embryo/egg freezing or GnRH agonist co-administration (leuprorelin) during treatment.
Haemorrhagic cystitis: mesna inactivates acrolein (toxic metabolite). For oral cyclophosphamide — high fluid intake and twice-daily voiding; for IV — mesna mandatory.
Secondary bladder cancer risk persists for years — monitor with urine dipstick/cytology in long-term follow-up (MHRA)

Contraindications

Severe bone marrow suppression
Active bladder inflammation
Haemorrhagic cystitis
Pregnancy (teratogenic)

Side effects

Haemorrhagic cystitis (prevent with mesna and hydration)
Bone marrow suppression (nadir 7-14 days)
Infertility (ovarian failure, azoospermia — discuss fertility preservation before treatment)
Secondary malignancy (bladder cancer, haematological)
Nausea/vomiting
Alopecia
Opportunistic infections

Interactions

Allopurinol — increases cyclophosphamide toxicity
Warfarin — unpredictable INR changes
Live vaccines — contraindicated

Monitoring

FBC (weekly initially — nadir day 7-14)
Urinalysis (haemorrhagic cystitis)
LFTs
eGFR
Urine culture before each cycle
Disease activity (ANCA, complement, urinalysis)

Reference: BNFc; BNF 90; CYCLOPS Trial (de Groot et al. Ann Intern Med 2009); Euro-Lupus Nephritis Trial (Houssiau et al. 2002); KDIGO Vasculitis 2021; SPC Endoxana. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways