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Use of cyclophosphamide in rheumatic diseases
- • Available formulations: 25-and 50-mg tablets; 100-, 200-, 500-, and 1000-mg vials.
- • Dosage: multiple dosing regimens including (1) daily oral, 50 to 200 mg (0.7–2 mg/kg per day); (2) monthly IV, 0.5 to 1 g/m 2 body surface area or 15 mg/kg; and (3) 500 mg IV every 2 weeks for 6 doses (Euro-Lupus).
Pearl: dose of cyclophosphamide is based on actual body weight even if patient is obese.
- • Cost (150 mg/day): oral generic tablets $1100/month.
- • Follow-up: daily dosing, CBC every 2 weeks until stable dose, then monthly; serum creatinine, blood urea nitrogen, and electrolytes every 2 to 4 weeks, liver transaminases every 4 weeks. Urinalysis monthly while on therapy; urinalysis with cytology every 12 months after cessation of therapy. For monthly dosing, CBC, urinalysis, and pregnancy test (women) before each dose, CBC 10 to 14 days after each dose to see nadir. If total white blood cell (WBC) count falls below 3500/mm 3 or neutrophil count falls below 1500/mm 3 at the nadir, the dose should be reduced by 20% to 25%. If the nadir total WBC count is above 4000/ mm 3 , the dose may be increased if patient’s disease is not controlled.
- • Precautions: avoid in pregnancy, avoid live vaccines, use lower doses in elderly due to less bone marrow reserve (cellularity = 100%–age). Cimetidine and allopurinol increase frequency of leukopenia. IV cyclophosphamide interferes with stable Coumadin dosing.
A study review included 31 patients taking cyclophosphamide and 39 patients taking placebo. Patients taking cyclophosphamide had improved tender and swollen joint scores. Patients receiving placebo were six times more likely to discontinue treatment because of lack of treatment effect than patients receiving cyclophosphamide.
Withdrawals from adverse reactions were higher in the cyclophosphamide group. Side effects from cyclophosphamide included hemorrhagic cystitis, nausea, vomiting, leucopenia, thrombocytopenia, alopecia, amenorrhea and herpes zoster infections.
Cyclophosphamide appears to have a clinically and statistically significant benefit on the disease activity of patients with rheumatoid arthritis. But due to serious side effects, its use should remain limited to patients who have failed treatment with various other therapies.
Sources
- Suarez-Almazor ME, Belseck E, Shea B, Wells G, Tugwell P. Cyclophosphamide for rheumatoid arthritis. Cochrane Database Syst Rev. 2000;2000(2):CD001157. doi: 10.1002/14651858.CD001157. Update in: Cochrane Database Syst Rev. 2000;(4):CD001157. doi: 10.1002/14651858.CD001157. PMID: 10796419; PMCID: PMC8407281.https://pmc.ncbi.nlm.nih.gov/articles/PMC8407281/
