Cyclophosphamide (Nephrology)

Source: UK SPC (eMC) for Cyclophosphamide 1000 mg Powder for Solution for Injection or Infusion, section 4.2 (https://www.medicines.org.uk/emc/product/3525/smpc). The dose above is the SPC's 'Autoimmune diseases' regimen — the nephrology-relevant heading (e.g. lupus nephritis, ANCA-associated vasculitis); the SPC gives no separate nephrology or renal-indication-specific regimen. DOSAGE MUST BE INDIVIDUALISED: doses, duration and treatment intervals depend on the therapeutic indication, the combination regimen, the patient's general state of health and organ function, and 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, dose reduction or extension of therapy-free intervals may be necessary. RESTRICTION (section 4.3): cyclophosphamide should NOT be used in the management of non-malignant disease, except for immunosuppression in life-threatening situations. HYDRATION: prior to, during and immediately after administration, adequate amounts of fluid should be ingested or infused to force diuresis and reduce the risk of urinary tract toxicity; cyclophosphamide should therefore be administered in the morning. SPECIALIST USE ONLY: should only be used by clinicians experienced in cancer chemotherapy, and only where facilities exist for regular monitoring of clinical, biochemical and haematological parameters before, during and after administration, under the direction of a specialist oncology service. OTHER (ONCOLOGY) REGIMENS IN THE SAME SPC — do NOT mix with the autoimmune regimen: haematologic and solid tumours, daily treatment 3 - 6 mg/kg body weight (= 120 - 240 mg/m2) IV; intermittent treatment 10 - 15 mg/kg (= 400 - 600 mg/m2) IV with therapy-free intervals of 2 to 5 days; high-dose intermittent treatment 20 - 40 mg/kg (= 800 - 1600 mg/m2) IV with therapy-free intervals of 21 to 28 days. As preparation for bone marrow transplantation: 60 mg/kg IV for 2 days, or 50 mg/kg IV for 4 days; if a busulfan-cyclophosphamide (Bu/Cy) regimen is used, the first cyclophosphamide dose must be given at least 24 hours after the last busulfan dose. DOSE MODIFICATION FOR MYELOSUPPRESSION (SPC table): leukocytes above 4000/microlitre AND platelets above 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. Further dose reductions may be needed in combination therapy. Leukocyte and platelet counts should be performed regularly, and urinary sediment checked regularly for erythrocytes. HEPATIC IMPAIRMENT: severe hepatic impairment may decrease activation of cyclophosphamide, altering effectiveness; the dose must be reduced in severe hepatic impairment, and a 25% dose reduction is recommended for serum bilirubin 3.1 - 5 mg/100 mL (0.053 - 0.086 mmol/L). ELDERLY: monitoring for toxicity and the need for dose adjustment should reflect the higher frequency of decreased hepatic, renal, cardiac or other organ function and concomitant disease or therapy. PAEDIATRIC: the SPC states only that cyclophosphamide has been administered to children and that the safety profile in paediatric patients is similar to that of the adult population — NO numeric paediatric dose is given, so paedDose is null. Verify any paediatric use against a children's formulary. HANDLING: reconstitution should be performed by trained personnel in a designated area; protective gloves should be worn; avoid splashing into the eyes; the material should not be handled by women who are pregnant or breast-feeding. SOURCE LIMITATION: eMC section 4.5 was NOT captured in this bundle — the interactions listed below are taken from section 7 of the US label (openFDA/DailyMed) and must be checked against the UK SPC. Sections 4.4 and 4.8 were truncated at the fetch limit.