Low dose methotrexate: patient monitoring

Last updated: March 09, 2020

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Patient monitoring is essential to mitigate the risk of acute and chronic toxicity with methotrexate. Recommendations do vary. The British Association of Dermatologists (BAD) have produced guidelines for the safe and effective prescribing of methotrexate for skin disease. These can be used in conjunction with local shared care guidelines.

1. Renal
Methotrexate is excreted mainly by the kidneys. Death secondary to myelosuppression is increased significantly in patients with renal dysfunction. Renal function should be measured prior to initiation, and then every 7 to 14 days for the first month. Once treatment is stabilised, renal function can be assessed every 2-3 months. Dose adjustment may be required if renal function changes. 

2. Haematological
Full blood count (FBC) should be measured prior to initiation, after one week and repeated every 1-2 weeks for the first month and until the dose is stabilised. Monitoring should then be performed every 2-3 months. A downward trend of FBC and neutrophil count can be a sign of methotrexate toxicity even if the absolute values are within range. More frequent monitoring may be required in patients with risk factors for toxicity. 

3. Pulmonary
Use of methotrexate can rarely cause interstitial lung disease but fatalities have been reported. Symptoms are non-specific and include dry cough and dyspnoea and patients typically present within one year of starting methotrexate. If pulmonary toxicity is suspected, patients should be referred for further investigation. 

4. Liver 
Methotrexate is associated with a range of adverse liver effects including hepatitis. In patients with psoriasis taking the drug long-term, hepatic fibrosis may also occur. Patients with pre-existing liver disease, or who at risk of developing liver disease may be more likely to develop fibrosis. 

Routine liver biopsy is not recommended for assessing hepatic fibrosis in patients taking methotrexate and liver function tests (LFTs) in isolation are inadequate. Therefore tests to measure markers for fibrosis have been developed. Procollagen peptide type III (PIIINP) is a marker that is used to monitor patients with psoriasis taking methotrexate.

PIIINP, LFTs, and assessment of risk factors for developing liver disease (e.g. alcohol etc.) should be undertaken at baseline. PIIINP and LFTs should then be undertaken at least every 3 months. 

5. Nausea
Nausea is one of the most common side effects with methotrexate. Some patients experience fairly mild nausea but in others it may be severe enough to affect compliance. It is dose-dependent and usually occurs within 12-24 hours of ingestion. Taking the medicine at bedtime or with food may help to reduce the severity. Folic acid might also help with reducing nausea but evidence is conflicting. Antiemetics and/or use of the parenteral route may also be helpful.

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