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Box 5 Method of administering methotrexate

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

In vasculitis, methotrexate is usually prescribed at a dose of 0.3 mg/kg/week, orally or subcutaneously. If the clinical and biological tolerance is satisfactory, the dose may be increased to 20 and then 25 mg/week to reach this dose after 4–6 weeks; that dose will then be maintained until the end of treatment
A supplement with folic acid (preferable to folinic acid, which is more expensive), at a dose of 10 mg/week, 48 h after taking methotrexate, is necessary to reduce its potential toxicity, in particular mucous and hepatic toxicity, and improve the therapeutic maintenance level
The pre-therapeutic assessment, often already carried out as part of the diagnosis of vasculitis, must include complete blood count, platelet count, liver enzymes, creatinine clearance, and chest x-ray
There is no consensus on the monitoring rate after the start of treatment, but biological monitoring every week for 1 month, then every month for 3 months, then every 3 months until stopping it is acceptable
Methotrexate is excreted by the kidney, and its use is not recommended if the glomerular filtration rate is less than 30 ml/min (even if the patient is on dialysis, the drug is not eliminated by dialysis), and must be reduced together with a dose reduction (by 7.5–20 mg/week) if the glomerular filtration rate is between 30 and 60 ml/min. Dehydration, stimulated by fever or a diarrheal episode, can be a source of poisoning, especially in the elderly
The combination of methotrexate and sulfamethoxazole/trimethoprim increases the risk of hematological toxicity. This combination is not recommended. If prescribed, it should be done with extreme caution and requires close monitoring. In this situation, it is better to offer aerosols of 300 mg of pentamidine every 21–28 days or even atovaquone (750 mg × 2/day) as a prevention of pneumocystosis rather than sulfamethoxazole/trimethoprim
When the withdrawal phase of methotrexate is started, a decrease in methotrexate by 5 mg every month is possible at the end of treatment, before it is stopped
In the event of an acute infectious episode, discontinuation of methotrexate is recommended temporarily after a discussion with the referring doctor
 
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