Methotrexate 10mg Tablets Safe Prescribing

In autoimmune conditions and less commonly, in some cancer therapy regimens, methotrexate should be taken once a week; however, there continues to be reports of inadvertent overdose due to more frequent dosing.

The MHRA released a drug safety update in September 2020 which highlighted actions for healthcare professionals to take to reduce the risk of inadvertent overdose due to taking the wrong dose or due to more frequent dosing (including daily administration).

Between 1st January 2006 and up to 30th July 2020, there were eleven yellow card reports of serious toxicity associated with inadvertent daily dosing of once weekly methotrexate in the UK, with four of these reports being since January 2016.

Overdose of methotrexate can lead to serious adverse effects such as haematopoietic disorders (leukopenia, thrombocytopenia, anaemia, and pancytopenia) and gastrointestinal reactions (mucositis, stomatitis, oral ulceration, gastrointestinal ulceration, and gastrointestinal bleeding).

Some reports of overdose have been fatal. In the fatal cases, events such as sepsis or septic shock, renal failure and aplastic anaemia were reported.

A European review was completed and new recommendations made, which can be found here.

The prescribing of both 10mg and 2.5mg tablets increases the risk of overdose, the patient should just receive one strength, the 2.5mg tablets, with full information on what dose, including the total dose in milligrams and the number of tablets they need to take.

Following on from these recommendations Lincolnshire Integrated Care Board recommend:

• Methotrexate should only be prescribed by healthcare professionals who are fully aware of the benefits and risks of treatment and who have all necessary prescribing competence.
• All specialities, including haematology, should prescribe oral methotrexate doses in multiples of 2.5mg and the total dose in milligrams must also be included.
• Methotrexate 10mg tablets must not be prescribed or supplied.
• When oral methotrexate is prescribed as a once weekly dose, the prescription and the dispensing label must clearly show the dose in milligrams and the number of tablets to be taken with the frequency as “once a week on….” (The day of the week should be specified in full).
• Prescribing of methotrexate with co-trimoxazole or trimethoprim should be avoided and should not occur under any circumstances. This also applies to people who have recently taken methotrexate. *In exceptional circumstances, specialist paediatric services may use co-trimoxazole as prophylaxis, with watchful increased monitoring, for Pneumocystis pneumonia in children on immunosuppressive triple therapy that includes low dose methotrexate for inflammatory bowel disease or for leukaemia patients on maintenance methotrexate treatment. The specialist paediatric service will prescribe, supply, and monitor treatment.
• The patient/carer should be provided with full and clear dosing instructions on the once weekly dosing and decide together with the patient/carer on which day of the week they take the methotrexate. The day of the week should be noted in the patients record.
• All patients should be provided with full information about the methotrexate and know what the signs of methotrexate toxicity are.
• Monitoring requirements should be discussed with the patient/carer and follow up appointments booked. The importance of attending these appointments should be highlighted to the patient.

Further reading

MHRA Drug Safety Update - Here

BNF information - Here

Summary of Product Characteristics - Here

Lincolnshire Formulary - Here

Lincolnshire Prescribing & Clinical Effectiveness website - Here

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MHRA and CAS Alerts

Drug Recalls & National Patient Safety Alerts

This document explains the different levels of recall that the MHRA cascade out – MHRA recall information

All GP practices should have a nominated person to lead on MHRA alerts/Safety issues. They should be signed up to the alerts system and have a procedure to follow to manage them within the practice. This is a CQC requirement. If you require any support with this, you can email the MSO inbox below.

To sign up for the alerts click here.

Latest field safety notices can be found here.

New contact email for the Medication Safety Officer within the ICB – licb.mso@nhs.net

Medicine Safety Information

The team are now encouraging practices to sign up to the Medicines Supply Tool via the Specialist Pharmacy Service (SPS) website. Sign up is free, but requires an nhs.net email.

The tool provides the latest information on supply issues, actions to take and alternatives to use.

For a summary of the latest MHRA alerts, please see the monthly MHRA newsletter.

For the latest Medicines and Healthcare products Regulatory Agency (MHRA) alerts, please use the link below:

Levothyroxine Dosing Highlight

Background

Levothyroxine is primarily used to treat hypothyroidism; the dosing will vary based on the individual patient’s blood results.

The patient's Thyroid Stimulating Hormone (TSH) level will usually be measured every three months until stabilised (two similar measurements within the reference range, three months apart), monitoring will be then continued on an annual basis unless the patient has any symptoms.

Levothyroxine Tablets are available in five different strengths, 12.5mcg, 25mcg, 50mcg, 75mcg & 100mcg. The tablets are manufactured by many different companies and come in various coloured boxes with tablet size varying between manufacturers.

Dosing issues & review

When reviewing a patient who takes Levothyroxine one of the most important questions to ask is what dose are you currently taking? If possible, ask them to show you the boxes.

Many people take numerous strengths of tablet to make up their dose, so confirming what they are actually taking can be a vital part of finding out why their bloods are fluctuating. It could be that the Pharmacy has changed brand but the patient is taking the tablets from the colour of the box, or that they are not aware they should be taking more than one strength at the same time to get the correct dose.

There have been numerous incidents where the patient’s TSH levels are fluctuating, the dose has been adjusted in line with the bloods for there then to be little to no effect on the next blood results. When reviewed by the practice pharmacist it has become apparent that the patient was not taking the correct dose; this has been either due to lack of patient counselling e.g., new strength given, and the patient hasn’t been informed they need to take both/all the strengths they have to make the correct dose, or the patient usually takes a tablet from the green box and one from the blue so if the manufacturer changes this could result in the wrong dose being taken.

Speaking with the patient before making any adjustment to medications to determine what dose they are taking can help with stabilising the patient on the medication, this results in better treatment outcomes.

Important counselling points

• Ensure the patient knows what dose they should be taking; confirm they understand the combination of strengths needed to make up the dose if needed.
• Inform the patient that they should take the levothyroxine 30-60 minutes before breakfast, caffeine-containing liquids, or other medication
• Check the patient is aware of the routine monitoring required when taking levothyroxine and how important it is to attend for scheduled blood tests

Medication Safety Matters

Welcome to our Medication Safety Matters section, here we will keep you updated with all the latest matters relating to Medication Safety. This will include any local or national issues, MHRA drug recalls & alerts, trends within medication related incidents and learning that can help improve patient safety across the system. If you require any further information or guidance around medication safety please contact: licb.mso@nhs.net