How to manage methotrexate in patients with rheumatoid arthritis (RA)?
Intro
As a clinical pharmacist, the first-line treatment for rheumatoid arthritis is usually methotrexate. It is often as effective as using a biologic medication alone and is generally considered safer. It is important to support patients in improving their ability to tolerate methotrexate so that they don't stop taking it unnecessarily.
Management approach
Dosage scenario of MTX
Oral methotrexate should be started at 10–15 mg/week, with escalation of 5 mg every 2–4 weeks up to 20–30 mg/week, depending on clinical response and tolerability; parenteral administration should be considered in the case of inadequate clinical response or intolerance. When starting methotrexate or increasing the dose, ALT with or without AST, creatinine and CBC should be performed every 1–1.5 months until a stable dose is reached and every 1–3 months thereafter; clinical assessment for side effects and risk factors should be performed at each visit.
Folate deficiency due to methotrexate can contribute to mouth sores, nausea, vomiting, and liver toxicity. Replacing folate can help alleviate these problems and improve methotrexate adherence. Recommend folic acid 5 to 7 mg/week, either once per week or 1 mg daily. Don't be concerned about giving daily folic acid on the same day as methotrexate.. There's no proof this reduces methotrexate efficacy. Methotrexate should be stopped if there is a confirmed increase in ALT/AST greater than three times the upper limit of normal (ULN), but may be reinstituted at a lower dose following normalization. If the ALT/AST levels are persistently elevated up to three times the ULN, the dose of methotrexate should be adjusted; diagnostic procedures should be considered in the case of persistent elevated ALT/AST more than three times the ULN after discontinuation. Gastrointestinal (GI) side effects tend to worsen as oral methotrexate doses increase. If needed, recommend splitting a once-weekly oral dose into 2 or 3 doses given 12 hours apart or switching to an injectable.
Drug interaction
Trimethoprim/sulfamethoxazole (TMP/SMX) or proton pump inhibitor (PPI) interactions can increase methotrexate levels and the risk of toxicity. Avoid TMP/SMX or recommend holding methotrexate if it's needed. Suggest using an H2-blocker (famotidine, etc) instead of a PPI or monitoring for toxicity if a PPI is necessary. NSAIDs may come up as a flagged interaction. But explain this is only a problem with the higher doses of methotrexate used for cancer
Dosing errors can occur if a methotrexate therapy is accidentally written for once daily instead of once weekly. Consider adding the day of the week methotrexate should be taken to the Rx label to reduce confusion. Methotrexate can be safely continued in the preoperative period in rheumatoid arthritis (RA) patients undergoing elective orthopedic surgery. Methotrexate should not be used for at least 3 months before planned pregnancy for men and women and should not be used during pregnancy or breast feeding.
References
- Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2009;68(7):1086-1093.
- Kremer JM. Use of methotrexate in the treatment of rheumatoid arthritis. UpToDate, Connor RF (Ed), Wolters Kluwer. Available at: https://www.uptodate.com/contents/use-of-methotrexate-in-the-treatment-of-rheumatoid-arthritis.
