Name of medicine / Methotrexate
Oral 2.5mg Tablets
Injection 50mg/ml
Indication
(including whether for adults and/or children) / Licensed: Rheumatoid arthritis and severe psoriasis in adults
Unlicensed: Psoriatic arthritis and Crohn’s disease in adults
PCN policy statement reference
(if applicable) / Not applicable
Author(s): Georgina Randall, Senior Commissioning Technician, 5th July 2016
Organisation(s): Medicines Management (Hosted Service), Surrey Downs CCG
Version: 1 / PCN recommendation date: 05-Apr-17 / Review date: Apr-2020
The Shared Care Guideline (SCG) is intended to facilitate the accessibility and safe prescribing of complex treatments across the secondary/primary care interface.
This AMBER shared care document sets out the patient pathway relating to this medicine and any information not available in the British National Formulary and manufacturer’s Summary of Product Characteristics. Prescribing must be carried out with reference to those publications.
The SCG must be used in conjunction with the PCN agreed core roles and responsibilities stated in annex A.
An agreement notification form is included in annex B for communication of request for shared care from provider and agreement to taken on prescribing by primary care
Roles and Responsibilities
Listed below are specific medicine/indication related responsibilities that are additional to those core roles and responsibilities that apply to all SCGs listed in annex A.
Consultant or Specialist responsibilitiesPre-treatment checks:-
1. Confirm diagnosis and indication for treatment with oral methotrexate, 2.5mg tablet strength.
2. Prior to treatment ask Primary Care Prescriber whether patient has had pneumococcal vaccination and flu vaccination and, if not, immunise (unless contra-indicated). Inform patient not to start medication until after immunisation.
3. Exclude existing pregnancy in women with child bearing potential.
Patient education:-
4. To discuss fully the aims, benefits, risks and side effects of treatment and the intended treatment plan with the patient and/or carer and for written information to be supplied to the patient and/or carer.
5. Explain that the medication is always taken once a week.
6. Inform patients to report immediately any exposure to Varicella Zoster Virus.
7. To discuss the potential implications of pregnancy and breastfeeding in women of child bearing potential and agree a risk minimisation strategy where appropriate.
8. Discuss the possibility of shared care with the patient and/or carer and ensure that they understand the plan for their subsequent treatment.
Starting of treatment:-
9. To initiate treatment by prescribing and monitoring (as per monitoring section below) usually for a minimum of 3 months.
10. To initiate concurrent folic acid
Subsequently:-
11. Monitor and prescribe according to guidelines until handover is appropriate (including when dose changes are made).
Shared care:-
12. Supply Primary Care Prescriber with a summary of the patient’s review (including anticipated length of treatment) and a link to, or a copy of, the shared care guideline when requesting transfer of prescribing to GP or primary care prescribers.
13. Ensure that the patient has been given a copy of this guideline, and if not, supply a copy to them.
Methotrexate Injection
14. When the decision is made to commence methotrexate injection supply licensed methotrexate pre-filled syringe (Metoject®) and a purple lidded cytotoxic sharps bin.
15. Provide training on self-administration of subcutaneous methotrexate injection using specialists trained in the handling of cytotoxic drugs. Training will include risk assessment, safe storage, handling and disposal, including spillage as per RCN guidance.
16. Provide a copy of the Metoject® patient guide.
17. Ensure patient will be supervised for a minimum of two injections or until competent to transfer to primary care.
18. Inform the GP that the patient has been switched to methotrexate injection and of the dose.
GP or Primary Care Prescriber responsibilities
1. Add information about the medicine to patient record, initially as “hospital prescribed”, and highlight the importance that this medicine is only to be prescribed under a shared care guideline in primary care.
2. Ensure that the patient has been given a copy of this guideline, and if not, supply a copy to them.
3. Explain that the medication is usually taken once a week.
4. Provide patient with pneumococcal vaccination and flu vaccination unless contra-indicated or already give pre-treatment.
5. Inform patients to report immediately any unexplained bleeding, bruising, purpura, sore throat, fever, pallor, jaundice or malaise and take the actions outlined in this shared care guideline
6. Inform patients to report immediately any exposure to Varicella Zoster Virus.
7. Continue prescribing of oral methotrexate, 2.5mg tablet strength, at the dose recommended and undertake monitoring requirements.
8. Prescribe folic acid tablets to reduce adverse events as recommended by consultant.
9. Prescribe any change in methotrexate dose as advised by the specialist team and monitor (as per monitoring section below)
10. Update the patient held record book, when possible.
Methotrexate injection
11. Provide the patient with prescriptions for Metoject® as advised by the specialist, and a purple lidded cytotoxic sharps bin as required
12. Ensure systems are in place for the patient to receive their weekly injection if they are not self-administering
13. Ensure patients have their injection technique reviewed at least yearly by a specialist nurse
Patient's or Carer’s role
Please ensure that you read and understand your responsibilities with regards to your treatment, as listed in Annex A of this document
In addition to these it is important to be aware of the following:–
1. Report immediately to your doctor, if you come into contact with someone with Varicella Zoster Virus (e.g. chicken pox or shingles).
2. Report immediately to your doctor, the start of any feature of:
· blood disorders (e.g. sore throat, bruising, and mouth ulcers)
· liver toxicity (e.g. nausea, vomiting, abdominal discomfort, and dark urine)
· respiratory effects (e.g. shortness of breath)
· fever
3. Keep all appointments with your healthcare providers (i.e. GP, consultant, specialist, nurse, pharmacist). Appointments will include those required for testing that methotrexate is being effective and that it is not causing any side effects.
4. Bring your hand-held monitoring booklet to all appointments with all of your healthcare providers (i.e. GP, consultant, specialist, nurse, pharmacist) and to the pharmacy when obtaining prescription supplies.
5. Check the dose and strength of the tablets received at each supply against the most recent entry in your monitoring booklet. Question any differences with your pharmacist.
6. Avoid taking over-the-counter (non-prescription) medications including those containing aspirin and ibuprofen without the knowledge of the specialist team. Ask your pharmacist for advice when purchasing medicines.
Methotrexate injection
If using methotrexate injection, ensure that the used syringe (which is classified as hazardous waste) is disposed of appropriately. Check this with your pharmacist.
Key information on the medicine
Please refer to the current edition of the British National Formulary (BNF), available at www.bnf.org, and Summary of Product Characteristics (SPC), available at www.medicines.org.uk for detailed product and prescribing information and specific guidance.
Background to use for the indications, including licence status:
Methotrexate 2.5mg tablets are used as an immunosuppressant either alone or in combination with other agents which influence the immune response. Local consultants often use methotrexate in combination with leflunomide, sulfasalazine and hydroxychloroquine.
Methotrexate is licensed in the UK for the treatment of rheumatoid arthritis and psoriasis.
Time to response: 6 weeks to 3 months.
ONLY prescribe the 2.5mg strength of tablets, the dose being multiples of the 2.5mg tablet strength once a week.
All patients should have an NPSA shared care booklet (purple), which patients should be encouraged to use to record details of blood results and for the clinician to record any dose changes.
Indication
Inflammatory Arthritis, Psoriasis, Crohn’s disease (unlicensed)
Dosage and Administration
Methotrexate is given ONCE weekly on the same day each week, swallowed whole with a glass of water one hour after food while sitting or standing. The tablets should not be crushed or chewed.
The doses used in practice may not correspond with BNF or SPC dosage ranges.
If oral administration causes intolerance, or the maximum oral dose is not effective, the parenteral route of administration will be considered.
Folic acid should be prescribed routinely at a dose of 5 mg weekly, to be taken at least 24 hours after the Methotrexate. Folic acid can be given at an increased dose e.g. 10mg and / or more frequently but NOT on the day of Methotrexate. Folic acid reduces the risk of hepatotoxicity and gastrointestinal side effects and improves compliance.
Methotrexate injection
Metoject® is the only licensed preparation available for inflammatory arthritis and psoriasis. It is available as pre-filled syringes and should be stored at room temperature and out of sight and reach of children. Licensed dose range is 7.5mg – 30mg WEEKLY.
Metoject® is a cytotoxic drug and is therefore classified as hazardous waste and must be disposed of in a purple topped cytotoxic sharps bin. At least the initial cytotoxic sharps bin will be provided by the acute trust. Disposal arrangements will vary according to the policy of the local borough council and are available at: http://pad.res360.net/Content/Documents/Disposal%20of%20Domestic%20Cytotoxic%20Sharps%20Waste%20Feb2012%20FINAL.pdf
This information sheet does not replace the SPC, which should be read in conjunction with this guidance. www.medicines.org.uk. Prescribers should also refer to the appropriate paragraphs in the current edition of the BNF.
Monitoring
Blood samples may be taken at the patient’s Primary Care Prescriber practice whenever this avoids a patient attendance in secondary care. Where the specialist is responsible for monitoring, they need to have the appropriate systems to capture the testing.
Monitoring requirements and appropriate dose adjustments / Responsible clinicianPre-treatment:
· FBC, U&Es, creatinine, LFTs ESR and / or CRP and usually CXR. Pulmonary function tests should be considered in selected patients e.g. abnormal shadowing on CXR.
· Consider NICE (PH guidance 43) recommendations regarding screening for hepatitis B and C in patients at increased risk of infection. / Specialist
Initiation:
FBC, U&E, creatinine, LFTs, ESR and / or CRP every 2 weeks until dose of methotrexate and monitoring stable for 6 weeks, then every month for 3 months / Specialist
Maintenance:
FBC, U&Es, creatinine, LFTs, ESR and / or CRP every 2 months, with due consideration for risk factors. This can be extended to 3 months at the specialist’s discretion.
Increased dose change when on maintenance:
· FBC, U&E, creatinine, LFTs, ESR and / or CRP every 2 weeks after a dose change until dose and monitoring stable for 6 weeks. Then revert to monitoring as per maintenance.
· Monitor for adverse drug reactions throughout treatment.
· Check for drug interactions on initiating new treatments. / Specialist until Primary care prescriber has accepted transfer of care.
Test / Abnormal Result / Action if Abnormal Result
WBC / <3.5 X 10^9/l / Repeat WBC in 1/52, if normal continue, if trend downwards, withhold and discuss with specialist dept.
Neutrophils / <1.5 X 10^9/l / Repeat WBC in 1/52, if normal continue, if trend downwards, withhold and discuss with specialist dept.
Platelets / <150 X10^9/l / Repeat WBC in 1/52, if normal continue, if trend downwards, withhold and discuss with specialist dept.
Liver function / AST/ALT >twice upper limit of reference range / Exclude intercurrent illness or new medication. Repeat LFTs in 1/52. If worsening, withhold and discuss with specialist
Albumin / Unexplained fall (in absence of active disease) / Exclude intercurrent illness. Repeat in 1-2/52. If worsening, withhold and discuss with specialist
MCV / >105 fl / Check serum B12, Folate and TFT and treat. If normal, continue treatment. Clinically non significant macrocytosis is common.
Significant deterioration in renal function / Creatinine >30% above baseline/ eGFR<50 / Withhold until discussed with specialist; dose adjustment may be needed
Rash, oral ulceration, nausea and vomiting, diarrhoea, stomatitis / Exclude intercurrent illness. Increased folic acid (eg 5mg daily except day of MTX dose) may alleviate symptoms. Otherwise withhold until discussed with specialist.
New or increasing dyspnoea/cough / Assess chest and withhold treatment. Urgent CXR. Discuss urgently with specialist.
Severe sore throat, abnormal bruising / Withhold treatment and check FBC urgently. Admit if pancytopenic. Alert specialist.
Cautions, contraindications - Refer to current Summary of Product Characteristics (SPC): www.medicines.org.uk
Adverse effects - Refer to current Summary of Product Characteristics (SPC): www.medicines.org.uk
Drug interactions - Refer to current Summary of Product Characteristics (SPC): www.medicines.org.uk
Notable drug interactions:
· Co-trimoxazole, trimethoprim: Antifolate effect of methotrexate is increased and greatly increases the risk of marrow aplasia. DO NOT prescribe folate antagonists to patients on methotrexate.
· Acitretin, chloramphenicol, nitrous oxide, tetracyclines and any drugs with suspected or confirmed hepatotoxic or nephrotoxic effects.
· Phenytoin: Antifolate effect of methotrexate is increased.
· Probenecid, penicillin, non-steroidal anti-inflammatory drugs (NSAIDs): Methotrexate excretion is reduced. (Clinically significant interaction between NSAID and methotrexate is rare. There are no contra-indications to using standard doses of NSAIDs with doses of weekly methotrexate ≤ 30mg as long as the required methotrexate monitoring is undertaken as salicylates and some other NSAIDs delay the excretion of methotrexate. National guidance relating to cardio-vascular, gastro-intestinal and renal risk should be followed).
· Inactivated vaccines such as influenza vaccine are safe to use although they may elicit a lower response.
Live Vaccines - AVOID. Severe or fatal infections may occur if a live vaccine is given concurrently. Therapy with a single, low-dose, non-biological oral immune modulating drug for treatment of rheumatoid arthritis and other conditions (e.g. methotrexate less than 0.4mg per kg per week) is not necessarily sufficiently immunosuppressive to contraindicate administration of zoster vaccine, so herpes zoster vaccine is not contraindicated in these patients (see http://tinyurl.com/nvdeqp2 ). The degree of immunosuppression should be assessed on a case by case basis. Primary care professionals with concerns about the degree of immunosuppression should contact the relevant specialist for advice.
Surgery - It is safe to continue with Methotrexate during surgical procedures, evidence suggests that there is no increased risk of post operative infection, and a flare of symptoms is potentially more harmful.