Methotrexate Toxicity Quantified Save

Methotrexate (MTX) is a highly favored drug in rheumatology.  Yet it has numerous nuisance side effects that may limit its use or patient acceptance.

Fatimah and coworkers have assessed a cohort of 150 rheumatoid arthritis patients taking MTX and studied drug tolerance using the methotrexate intolerance severity score (MISS) questionnaire. The MISS questionnaire embodies five elements: abdominal pain, nausea, vomiting, fatigue and behavioural symptoms.

One-third of the RA patients exhibited MTX intolerance according to the MISS questionnaire. Out of which, the most recurring symptom was behavioural (44%) and least common being vomiting (11%).

Not surprisingly, the highest rates of intolerance were associated with the highest doses of MTX (up to 20 mg). They also noted that intolerance rates were not affected by the use of other disease-modifying agents.

This trial did not address the role and impact of folate or how to best manage MTX toxicity, especially nausea, vomiting and post-MTX CNS effects or the "blahs".  Management pearls for these issues have been previously published on RheumNow and are summarized below:

• Higher doses = more toxicity.
• Parenteral dosing leads to higher drug levels and, consequently, more toxicity (not less as is commonly thought).
• Folate supplementation has been shown to be effective at lowering the frequency of GI side effects, protective against hepatic enzyme elevations and reduces the frequency of MTX discontinuations.
• Oral ulcerations, nausea and vomiting usually respond to either lower MTX doses, more folate or daily vitamin A 8000 Units/Day (I prefer the latter).
• Post-MTX "blahs" - use dextromethorphan (20-50mg) weekly and give with the MTX dose and again 8-12 hours later. We usually prescribe this as a tablet (Mucinex DM).
• Hepatic enzyme elevations - look for other causes, reduce the dose of MTX and take folic acid.