Subcutaneous methotrexate - shared care protocol

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Drug and Indication

Generic drug name



Metoject® pre-filled pen 50mg/ml for subcutaneous injection. Available as 7·5mg, 10mg, 12·5mg, 15mg, 17·5mg, 20mg, 22·5mg, 25mg, 27·5mg and 30mg pens.

Intended Indication

Adult patients with rheumatoid arthritis.

Status of medicine or treatment

Licensed for rheumatoid arthritis, psoriasis, active juvenile idiopathic arthritis.

  • Renal impairment (reduce dose to 50% if eGFR stable at 20 to 50ml/min and avoid if <20ml/min).
  • Hepatic impairment.
  • Patients with third distribution space (eg pleural effusion, ascites).


  • Liver insufficiency.
  • Alcohol abuse.
  • Pre-existing blood dyscrasia.
  • Pre-existing ulcers of oral cavity or active gastrointestinal ulcer disease.


  •  Hypersensitivity to methotrexate.
  • Serious acute or chronic infection (eg TB, HIV or other immunodeficiency syndromes).
  • Pregnancy and breast feeding – adequate contraception should be used by males and females during treatment and for at least 3 months after discontinuation.
  • Concurrent vaccination with live vaccines – see the Rheumatology Home Page on the Intranet (Vaccinations in the Immunocompromised Person).
  • Severe renal insufficiency (eGFR <20 ml/min).
Typical Dosage Regime

Route of administration

Subcutaneous injection.

Recommended starting dose

Will vary as directed by rheumatologist – normal starting dose for any route of methotrexate is 15mg per WEEK but may be lower if there is a history of intolerance.

Maximum dose

Generally 25mg per WEEK.

Adjunctive treatment

Folic acid should be prescribed for all patients – usually 5mg per week (the day after the methotrexate) but can be increased to 6 days per week excluding the day of the methotrexate. Previous NSAIDs can be continued. Anti-emetics can be co-prescribed.

Usual response time

May take up to 12 weeks to shows signs of response.

Duration of treatment



Undesirable Effects

ADR details


Nausea (very common)

Use of anti-emetics where necessary

Stomatitis (very common) and oral ulcers (common)

Folic acid dose can be increased up to 5 or 6 days per week (avoid on day of methotrexate).

Elevated transaminases (very common)

If over 2 x ULN then withhold and discuss with specialist team.

Blood cell dyscrasia (common)

If WCC <3.5x109/L, neutrophils <2.0x109/L or platelets <150x109/L or MCV >110 fl then withhold and discuss with specialist team. A drop in haemoglobin is very rare with methotrexate and other reasons for an isolated drop in haemoglobin should be considered.

Pneumonitis (common) – dry cough or increasing breathlessness

Withhold and discuss urgently with specialist team or if patient unwell or hypoxic and no specialist team available then with acute medical receiving.

Severe sore throat or abnormal bruising

Withhold and check FBC. If normal then methotrexate is not the cause.

Rash, diarrhoea (rare)

Usually has another cause but withhold and discuss with specialist team if no other cause apparent.


Drug Interactions (please see BNF/SPC for Metoject® for full list)
  • Trimethoprim or cotrimoxazole – increased risk of blood cell dyscrasia.
  • NSAIDs – avoid over the counter NSAIDs but when prescribed at low or stable dose then it would be rare to have issues at the doses of methotrexate used for rheumatological conditions.
  • Clozapine – increased risk of blood cell dyscasia.
  • Probenecid – excretion of methotrexate reduced.
  • Acitretin – plasma methotrexate levels increased with increased risk of liver toxicity.
  • Pyrimethamine – increased risk of blood cell dyscrasia.
  • Leflunomide/ciclosporin – increased risk of blood cell dyscrasias but still sometimes used when enhanced clinical effect required.
  • Cisplatin – increased pulmonary toxicity.
  • Antibiotics – unpredictable effect on methotrexate levels and we generally advise that if an antibiotic course is going to be over 1 week in duration then methotrexate is temporarily withheld.
Baseline Investigations
  • Please see responsibilities of acute care service which outlines the information given to the patient.
  • FBC, U&Es, LFTs within 3 months and CXR within 6 months of initiation.
  • PFTs are currently done in the majority of patients near the beginning of therapy where practical but treatment should not wait until the results being available unless this is stated in letter from specialist care. We are looking for a TLCO >70% to initiate methotrexate.
Monitoring (Primary Care)

Monitoring parameter


Laboratory Results

Action to be taken

Also note trends in values and any abnormal trends should provoke extra vigilance.

Full Blood COunt (FBC)

For those switching from oral methotrexate then monitoring will be the same as previously.


Initiation – 2 weekly for first 12 weeks then monthly for next 9 months and assuming that results remain normal then on to every 2 to 3 months depending on clinical judgement.


For those on combination DMARDs weekly for first 12 weeks then monthly for next 9 months and then assuming that results remain normal then on to every 2 months.

WCC <3.5x109/L


Platelets <150x109/L

MCV >110 fl.

Withhold and discuss with specialist team.

Urea & Electrolytes (U&Es)

Worsening renal function.

Withhold all nephrotoxins and temporarily suspend methotrexate.

Liver function test (LFTs)

ALT (or AST if available) >2x ULN

Albumin – unexplained drop.

Withhold and discuss with specialist team.

C-reactive protein (CRP)

CRP can be checked prior to a clinic visit or when there is a flare in symptoms. It is not a safety blood test but helps assess effectiveness of therapy.

Sudden unexpected rise in CRP.

Continue therapy and inform specialist team.

Severe sore throat, unexpected bruising or bleeding

Withhold all DMARDs.

Check FBC and if no abnormalities then look for other non drug related causes.

New dry cough or worsening breathlessness

Withhold all DMARDs.

If hypoxic or unwell then admit to acute medical receiving, otherwise inform specialist team.


Responsibilities of Acute Care (Consultant)
  1. To organise baseline investigations including CXR, bloods and if appropriate PFTs with documentation of CXR and blood results in notes. PFTs will not be reported other than in SCI store. Consultant will act on results of abnormal baseline investigations including PFTs.
  2. To clearly detail starting dose and any planned increments in dose to primary care with recommendation on monitoring.
  3. To provide patient with patient information leaflet relevant to DMARDs being commenced and to discuss with patient requirement for blood monitoring and side effects.
  4. To provide GP with GP information leaflet on DMARDs being prescribed by both electronic letter to GP either via letter handed to patient or by printed letter, ideally within 14 days of clinic appointment.
  5. To provide details on frequency of monitoring covering the first year, then can be at discretion of primary care team according to protocol.
  6. To provide advice to primary care on abnormalities in monitoring bloods or clinical side effects.
  7. To provide the first prescription of subcutaneous methotrexate for administration by specialist nurse.
  8. To provide all purple topped sharps bin to patients, and receive full bins from patients.
Responsibilities of Acute Care (Specialist Nurse)
  1. Training of patient in the administration of methotrexate by the subcutaneous route and supervision of first injection. If not practical then this has to be negotiated with nurse closer to home location and deviation from protocol documented in case notes.
  2. Education of patient on importance of monitoring.
  3. To explain risks of varicella in non-immune individuals and if uncertainty to organise baseline varicella serology.
  4. To provide advice to primary care on abnormalities in monitoring bloods or clinical side effects including appropriate referral back to consultant when it is likely to involve a significant long term change in treatment plan.
  5. Training of patient to deal with spillage and disposal of injections.
Responsibilities of Acute Care (General Practitioner)
  1. To monitor and prescribe (after first injection) in collaboration with the specialist according to this protocol. Prescriptions should normally be for 12 weeks duration, dispensed monthly.
  2. To ensure that the monitoring is kept up to date and consider withdrawing treatment if patient doesn’t comply with monitoring requirements.
  3. Symptoms or results are appropriately actioned, recorded and communicated to acute care when necessary and where there is suspension of treatment (except where methotrexate being withheld for temporary antibiotic course).
  4. Provision of pneumococcal and influenza vaccination.
  5. Avoiding co-prescription of interacting drugs except leflunomide, ciclosporin where advised by secondary care.
  6. To follow guidance on exposure to varicella in non-immune individuals –
Responsibilities of Patient
  1. To report adverse effects to their GP or specialist.
  2. To attend for GP visits and blood monitoring visits.
  3. To attend hospital appointments for specialist review.Failure of the patient to attend hospital or GP visits will result in medication being stopped.
Contact Numbers

Specialist Rheumatology Nurse (South of Dingwall area) 01463 704019.

Specialist Rheumatology Nurse (North of Dingwall area) 01349 868791.

Abbreviation Meaning
eGFR Estimated glomerular filtration rate
TB Tuberculosis
HIV Human immunodeficiency virus
WCC White cell count
MCV Mean corpuscular volume
ULN Upper Limits of Normal
NSAIDs Non-steroidal anti-inflammatory drugs
FBC Full blood count
U&Es Urea and elecrolytes
LFTs Liver function tests
CXR Chest X-ray
TLCO Transfer factor for carbon monoxide
PFTs Pulmonary function tests
ALT/AST Alanine aminotransferase/ Aspartate aminotransferase
Editorial Information

Next review: 30 September 2019

Document Id: TAM354