Cyclophosphamide (Rheumatology)

Source: UK SPC (eMC) for Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion, §4.2 (https://www.medicines.org.uk/emc/product/3525/smpc). The dose above is the SPC's 'Autoimmune diseases' heading - the only rheumatology-relevant regimen in this label; the SPC gives no separate rheumatology or indication-specific regimen (e.g. no named regimen for any individual connective tissue disease or vasculitis). IMPORTANT §4.3 RESTRICTION: 'Cyclophosphamide should not be used in the management of non-malignant disease, except for immunosuppression in life-threatening situations.' DOSAGE MUST BE INDIVIDUALISED: doses, duration of treatment and/or treatment intervals depend on the therapeutic indication, the scheme of combination therapy, the patient's general state of health and organ function, and the results of laboratory monitoring (in particular blood cell monitoring); the SPC states the listed doses 'can be regarded as general guidelines'. In combination with other cytostatics of similar toxicity, a dose reduction or extension of the therapy-free intervals may be necessary. PRESCRIBER RESTRICTION: cyclophosphamide should only be used by clinicians experienced in the use of cancer chemotherapy, only where there are facilities for regular monitoring of clinical, biochemical and haematological parameters before, during and after administration, and under the direction of a specialist oncology service. HYDRATION: prior to, during and immediately after administration, adequate amounts of fluid should be ingested or infused to force diuresis in order to reduce the risk of urinary tract toxicity; cyclophosphamide should therefore be administered in the morning. DOSE MODIFICATION FOR MYELOSUPPRESSION (SPC table): leukocytes greater than 4000/microlitre and platelets greater than 100,000/microlitre - 100% of the planned dose; leukocytes 2500-4000 and platelets 50,000-100,000 - 50% of the planned dose; leukocytes below 2500 or platelets below 50,000 - omit until values normalise or decide individually. In combination therapy further dose reductions may have to be considered. Leukocyte and platelet counts should be performed regularly and urinary sediment checked regularly for erythrocytes. HEPATIC IMPAIRMENT: the dose must be reduced in patients with severe hepatic impairment; a dose reduction of 25% is recommended in patients with serum bilirubin concentrations of 3.1-5 mg/100 ml (0.053-0.086 mmol/l). Severe hepatic impairment may be associated with decreased activation of cyclophosphamide, which may alter effectiveness. ELDERLY: monitoring for toxicities and the need for dose adjustment should reflect the higher frequency of decreased hepatic, renal, cardiac or other organ function and concomitant disease or drug therapy. PAEDIATRIC (no numeric per-kg paediatric dose is stated in §4.2): the SPC states only that 'Cyclophosphamide has been administered to children. The safety profile of cyclophosphamide in paediatric patients is similar to that of the adult population.' Verify any under-18 dosing against a children's formulary. HANDLING: reconstitution should be performed by trained personnel in a designated area; protective gloves should be worn, splashing into the eyes avoided, and the material should not be handled by women who are pregnant or breast-feeding. OTHER (NON-RHEUMATOLOGY) REGIMENS ON THE SAME LABEL, for context only - haematologic and solid tumours: daily treatment 3-6 mg/kg body weight (= 120-240 mg/m2), intravenously; intermittent treatment 10-15 mg/kg (= 400-600 mg/m2) intravenously with therapy-free intervals of 2 to 5 days; high-dose intermittent treatment 20-40 mg/kg (= 800-1600 mg/m2) intravenously with therapy-free intervals of 21 to 28 days; preparation for bone marrow transplantation 60 mg/kg for 2 days or 50 mg/kg for 4 days intravenously. US cross-check (openFDA, XGen Pharmaceuticals, label date 2024-12-20) covers malignant disease and paediatric minimal change nephrotic syndrome only and states no autoimmune-disease regimen.