Methotrexate

• Solution for injection vials 5mg/2ml, 50mg/2ml, 500mg/20ml, 1g/10ml
• Tablets 2.5mg (£1.64 = 28 tablets)
• Metoject PEN solution for injection pre-filled pen (£12.87 - £16.56 per syringe)
  • 0.15ml (7.5mg), 0.2ml (10mg), 0.25ml (12.5mg), 0.3ml (15mg), 0.35ml (17.5mg), 0.4ml (20mg), 0.45ml (22.5mg), 0.5ml (25mg), 0.55ml (27.5mg), 0.6ml (30mg)

Notes

1. Refer to individual shared care guidelines for use in Gastroenterology, Rheumatology, and Dermatology conditions
2. To avoid confusion for patients due to differences between injection devices, subcutaneous methotrexate should be prescribed by brand
3. Methotrexate Safety Information: Oral methotrexate is a very effective medication and acceptably safe if taken at the correct dose with the required monitoring. However, it has the potential for serious toxicity, compounded by confusion surrounding its unusual dosing schedule of once weekly. The National Patient Safety Agency has issued a safety alert with recommended actions to help reduce the number of drug errors associated with methotrexate. The full guidance can be viewed here. Some of the key points are summarised below.
   1. Patients should be issued with an information leaflet and monitoring document.
   2. Be aware that different strengths of methotrexate tablets are available. Where possible the patient should be supplied with one strength continuously which should be recorded in the monitoring booklet and can be checked by others to confirm supply details. If a patient describes their dose by the number of tablets, take care in ascertaining the strength of these tablets. Local policy is to use only 2.5mg tablets for oral once weekly methotrexate in adults varying the number of tablets to achieve the desired dose. If a different strength is stated, take extra steps to check the accuracy of this.
   3. When admitted to hospital a full medication review should be undertaken, preferably by a pharmacist, and the prescribing, monitoring and administration requirements recorded in the notes.
   4. It is the prescriber's responsibility to record the correct dose and frequency on the drug chart and to strike out the six days of the week when a dose must not be administered. Discharge prescriptions must be complete, legible and include the form, strength dose and directions in full. Staff administering oral methotrexate should confirm with the patient that the medication is required and then carefully check the details of strength, dose and timing together with their usual drug administration checks. The administration should be recorded on the drug chart at the time the dose is given.
   5. Be aware of patients who present with symptoms of breathlessness, persistent dry cough, vomiting or diarrhoea as these can be signs of methotrexate toxicity.
   6. Patients should be co-prescribed folic acid to prevent methotrexate-induced side-effects (off-label use). Prescribe 5mg at least once weekly (more frequent dosing is often routinely recommended, refer to individual shared care guidelines / specialist advice). Folic acid should be taken at least 24 hours after previous methotrexate administration. Be aware that methotrexate and folic acid tablets look alike.
4. MHRA Drug Safety Update (September 2020): Methotrexate once-weekly for autoimmune diseases: new measures to reduce risk of fatal overdose due to inadvertent daily instead of weekly dosing. 
   1. Advice for prescribers: before prescribing methotrexate, make sure that the patient is able to understand and comply with once-weekly dosing  
   2. consider the patient’s overall polypharmacy burden when deciding which formulation to prescribe, especially for a patient with a high pill burden  
   3. decide with the patient which day of the week they will take their methotrexate and note this day down in full on the prescription  
   4. inform the patient and their caregivers of the potentially fatal risk of accidental overdose if methotrexate is taken more frequently than once a week; specifically, that it should not be taken daily  
   5. advise patients of the need to promptly seek medical advice if they think they have taken too much 
5. MHRA Drug Safety Update (August 2023): Methotrexate: advise patients to take precautions in the sun to avoid photosensitivity reactions 
   1. Photosensitivity reactions are known side effects of methotrexate treatment and can occur with both low-dose and high-dose treatment.
   2. Reactions manifest as severe sunburn such as rashes with papules or blistering, with some patients reporting swelling; rarely, photosensitivity reactions have contributed to deaths from secondary infections.
   3. Healthcare professionals, including those prescribing and dispensing methotrexate, should remind patients to take precautions to protect themselves from the sun and UV rays.
   4. Refer to the safety update for advice to give to patients.

Pemetrexed

• Powder for solution for infusion vials 100mg, 500mg, 1g
• Solution for infusion vials 100mg/4ml, 500mg/20ml, 850mg/34ml, 1g/40ml

Notes

1. NICE TA124: Pemetrexed is not recommended for the treatment of locally advanced or metastatic non-small cell lung cancer (August 2007).
2. NICE TA181: Pemetrexed in combination with cisplatin is recommended as an option for the first-line treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) only if the histology of the tumour has been confirmed as adenocarcinoma or large-cell carcinoma (September 2009).
3. NICE TA402: Pemetrexed (Alimta) is recommended as an option for the maintenance treatment of locally advanced or metastatic non-squamous non-small-cell lung cancer in adults (August 2016), when:
   1. their disease has not progressed immediately after 4 cycles of pemetrexed and cisplatin induction therapy
   2. their Eastern Cooperative Oncology Group (ECOG) performance status is 0 or 1 at the start of maintenance treatment and
   3. the company provides the drug according to the terms of the commercial access agreement as agreed with NHS England.
   4. Refer to TA402 for additional considerations regarding performance status score.
4. NICE TA190: Pemetrexed (Alimta) is recommended as an option for the maintenance treatment of people with locally advanced or metastatic non-small-cell lung cancer other than predominantly squamous cell histology if disease has not progressed immediately following platinum-based chemotherapy in combination with gemcitabine, paclitaxel or docetaxel (August 2017).
5. NICE TA135: Pemetrexed is recommended as a treatment option for malignant pleural mesothelioma only in people who have a World Health Organization (WHO) performance status of 0 or 1, who are considered to have advanced disease and for whom surgical resection is considered inappropriate (January 2008).

Raltitrexed

• Powder for solution for infusion vials 2mg