Cyclophosphamide | Azathioprine | Chlorambucil | Methotrexate | Cyclosporine | Mycophenolate mofetil | Vincristine | |
Usual dose | 2–3 mg/kg OD PO 2–3 months; 0.5–1.0 g/m2 IV monthly with MESNA to prevent cystitis | 0.5–2.5 mg/kg OD PO for 1 year or more | 0.1–0.2 mg/kg/day for 3 months | 10–15 mg/m2/wk (single dose) PO | 3–5 mg/kg/day PO (in 2 divided doses) | 0.25–2 g/day (2 divided doses) PO | 1.5 mg/m2//wk IV (single dose) for 8 weeks (limited data for efficacy in FSGS) |
Serious side effects | Leucopenia; haemorrhagic cystitis; reversible alopecia; infertility; leukaemia, lymphoma, transition cell carcinoma of bladder | GI toxicity; hepatotoxicity; rash; leucopenia; teratogenicity; no increase in malignancy in adults with RA; no conclusive data for cancer risk in children | Marrow suppression; rash; toxic epidermal necrolysis; Stevens–Johnson syndrome; late risk of leukaemia? | Bone marrow suppression and interstitial pneumonitis (decreased risk with folic acid); reversible elevation of transaminases; hepatic fibrosis | Renal impairment; hypertension; hepatotoxicity; tremor; gingival hyperplasia; hypertrichosis; lymphoma | Bone marrow suppression; severe diarrhoea; pulmonary fibrosis | Reversible peripheral and autonomic neuropathy; SIADH; severe local irritation if extravasation; alopecia; constipation; myelosuppression rarely encountered |
Cumulative toxic dose | Not described for malignancy; 500 mg/kg for azoospermia | Not described | >18 mg/kg causes azoospermia; <10 mg/kg does not | Not described | Not described | Not described | Not described |
Clinical monitoring | Weekly FBC for duration of therapy (usually 2–3 months)2-150 | Weekly FBC for 2 months, then 3 monthly2-150 | Weekly clinical review and FBC for duration of therapy2-150 | Baseline CXR, FBC and LFTs | Weekly measurement of blood pressure | Weekly FBC for 2 months, then fortnightly for 2 months, then monthly | Baseline and monthly clinical review for neuropathy |
Baseline and monthly renal and liver function | Baseline and monthly renal and liver function for 2 months, then 3 monthly | FBC and LFTs every 2 weeks for 2 months, then monthly2-150 | Baseline and monthly renal function | Baseline monthly renal and liver function | Baseline and monthly FBC | ||
Temporarily discontinue if leucopenia <1.5 × 109l, platelets <100 × 109 l, or haematuria | Temporarily discontinue if leucopenia <1.5 × 109l, platelets <100 × 109 l | Reduce or discontinue if hepatic enzymes >3× upper limit of normal | Maintain 12 hour trough level at 50–100 ng/ml2-150
Baseline and 3 monthly GFR | Discontinue if leucopenia <1.5 × 109 l, platelets <100 × 109 l, or significant GI side effects | Discontinue if increasing neurotoxicity, especially motor weakness |
↵2-150 Personal practice.
OD, once daily; PO, orally; IV, intravenously; MESNA, sodium 2-mercaptoethanesulphonate; GI, gastrointestinal; RA, rheumatoid arthritis; FSGS, focal segmental glomerulosclerosis; SIADH, syndrome of inappropriate secretion of antidiuretic hormone; FBC, full blood count; CXR, chest x ray; LFT, lung function test; GFR, glomerular filtration rate.