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Box 6 Method of administering cyclophosphamide

From: French recommendations for the management of systemic necrotizing vasculitides (polyarteritis nodosa and ANCA-associated vasculitides)

Precautions before administration  
Fertility preservation should be ensured, or at least offered to patients, to women of childbearing age as well as to men  
Hydration prior to and during the infusion is essential. It is supplemented by the administration of mesna (off-label and without certainty of its value for doses of cyclophosphamide < 600 mg/m2 per bolus), administered during and after the cyclophosphamide infusion:  
One-third of the equivalent dose of cyclophosphamide (in milligrams) by IV bolus at hour 0  
Then two-thirds of the IV dose at the end of the infusion (90th minute)  
And two-thirds of the dose at hour 4, orally  
When cyclophosphamide is delivered orally, mesna can also be administered orally (equivalent daily dose in milligrams, orally—possible off-label use)  
Monitoring of the cyclophosphamide treatment is based on the complete blood count and platelet count, serum creatinine, and the search for hematuria as a minimum:  
Before each infusion  
Every 2 weeks for the first 3 months  
Then monthly if the oral treatment is continued  
If the neutrophils are < 1.5 × 109/L on the scheduled bolus date, the dose will be reduced by 25% or even postponed (trying not to postpone treatment for more than 2 weeks, in which case another therapy should be discussed)  
Cyclophosphamide administration regimen  
In patients with normal kidney function under 65 years of age, the recommended regimen is the following: IV bolus of cyclophosphamide prescribed at a dose of 0.6 g/m2 on days 1, 15, and 29; then 0.7 g/m2 every 21 days (total of six boluses)  
In patients with normal kidney function under 65 years of age, the recommended regimen is the following: IV bolus of cyclophosphamide prescribed at a dose of 0.5 g/m2 on days 1, 15, and 29; then 0.7 g/m2 every 21 days (total of six boluses)  
In patients over 65 years of age, regardless of kidney function, the recommended regimen is as follows: IV bolus of cyclophosphamide prescribed at a fixed dose of 0.5 g on days 1, 15, and 29, then every 21 days (total of six boluses). The benefit of this regimen has been demonstrated in the prospective CORTAGE trial, providing efficacy comparable to a conventional treatment but with better tolerance. These low doses of cyclophosphamide have not been evaluated compared to rituximab in this population  
In the event of incomplete remission, three additional boluses can be given  
The maximum dose of each bolus is limited to 1200 mg  
After induction therapy with cyclophosphamide, maintenance therapy should be started between 2 and 4 weeks after the last cyclophosphamide bolus, regardless of the maintenance therapy selected  
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