Published: 13 December 2017

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Methotrexate — Once Weekly Dosing

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Prescriber Update 38(4): 57-59
December 2017

Methotrexate is used to treat cancer and, in lower doses, to treat rheumatoid arthritis and psoriasis. Methotrexate interferes with folic acid metabolism and folic acid tablets are used to reduce adverse effect such as nausea or stomatitis¹.

Dosing

When methotrexate is used for rheumatoid arthritis, it is taken either once a week or in three divided doses over 36 hours once a week. Folic acid is normally prescribed to be taken on a different day to methotrexate. Treatment of psoriasis with methotrexate is also prescribed intermittently over a week. Additional dose information is included in the data sheets for methotrexate².

These are unusual dose regimens that may confuse some patients. It is important to clearly explain the dosing schedule to each patient and make sure they have understood the information. Specify on every prescription, and the dispensed medicine label, the day of the week (written in full) the dose is to be taken.

Healthcare professionals should also check that the patient is taking methotrexate correctly.

Serious and sometimes life-threatening or fatal adverse effects can be caused from incorrect methotrexate dosing².

Guidance on prescribing methotrexate safely has been published elsewhere^1,3.

Monitoring

It is imperative that monitoring of renal and liver function tests, full blood count and chest radiography occur before and during treatment. The Best Practice Advocacy Centre (BPAC) recommendations for monitoring methotrexate and management of methotrexate toxicity are outlined in Tables 1 and 2³. Please note that local guidelines may vary.

Table 1: Methotrexate monitoring recommendations³

Laboratory monitoring	Frequency	What to do if outside limits
Full blood count (FBC)	Baseline Every two to four weeks initially, then every month to three months if results have been normal on a stable dose.	Discuss with specialist team immediately.
Liver function tests (LFTs)	Baseline Every two to four weeks initially, then every month to three months if results have been normal on a stable dose.	Withhold until discussed with specialist team. Other factors to consider: Check alcohol intake. Review medicines which may cause liver dysfunction (eg, NSAIDs).
Serum creatinine	Baseline Often performed at same time as LFTs and FBC monitoring during dosing changes. Every three months for patients on stable treatment.	Reduce dose.
Chest X-ray	Baseline	Repeat if respiratory symptoms occur (see below).

Table 2: Management of methotrexate toxicity³

Symptoms	What to do
Rash or oral ulceration	Withhold methotrexate until discussed with specialist team. Folic acid mouth wash may help with mucositis.
Nausea and vomiting, diarrhoea	Dividing the dose over the day or giving methotrexate by subcutaneous injection is often a good way of avoiding nausea.
New or increasing dyspnoea or dry cough (pneumonitis)	Withhold and discuss URGENTLY with specialist team. Arrange chest x-ray and respiratory function tests.
Severe sore throat, abnormal bruising	Request immediate FBC and withhold until results available. Discuss any unusual results with specialist team.

Adverse effects

The risk of serious adverse effects is greater with higher doses and with prolonged methotrexate treatment. Hepatotoxicity may occur without previous signs of gastrointestinal or haematological toxicity. Pulmonary toxicity including pneumonitis and pulmonary fibrosis can also occur at any time during therapy. Methotrexate is usually contraindicated in patients with impaired renal function³.

At 30 September 2017, the Centre for Adverse Reactions Monitoring (CARM) had received eight cases in which a medication error was identified and methotrexate was assessed as a causal medicine. These cases included patients who had taken methotrexate in the prescribed dose every day of the week instead of once a week, patients who got the wrong strength of methotrexate tablets and a patient who had taken methotrexate without adequate monitoring.

Please continue to report any adverse events to methotrexate or any other medicine to CARM. Reports can be submitted on paper or electronically (https://nzphvc.otago.ac.nz/report/).

References

1. Waitemata Health Board. 2017. Methotrexate — Safe Prescribing — Once A Week! Safer Use of High Risk Medicines May 2017. URL: saferx.co.nz/full/methotrexate.pdf (assessed 22 November 2017).
2. Pfizer New Zealand Limited. 2017. Methotrexate DBL Data Sheet 25 August 2017. URL: medsafe.govt.nz/profs/Datasheet/d/dblMethotrexateinjmayne.pdf (assessed 22 November 2017).
3. Best Practice Advocacy Centre. 2014. Safer prescribing of high-risk medicines — Methotrexate: potentially fatal in overdose. Best Practice Journal 64: 48–52. URL: bpac.org.nz/BPJ/2014/October/docs/BPJ64-safer-prescribing.pdf (assessed 22 November 2017).