Subcutaneous methotrexate

• Methotrexate is recognised as the most effective of the traditional (non-biologic) disease modifying anti-rheumatic drugs (DMARDs) in current use for rheumatoid arthritis.
• The optimum therapeutic dose of DMARDs, particularly methotrexate, should be achieved to minimise disease progression and joint erosions.
• Parenteral methotrexate can:
  • Ensure the maximum bioavailability.
  • Reduce symptomatic side effects for some patients, allowing increases in the therapeutic dose to be better tolerated.
  • Extend the time that disease is controlled before anti-TNF therapies need to be introduced. BSR guidelines (2003) state that whenever possible patients should have received methotrexate at a target dose of at least 20mg per week before anti-TNF treatment is considered.
  • Improve the patients quality of life and satisfaction with treatment.

• Subcutaneous methotrexate is usually self-administered in doses of between 7.5mg and 30mg once weekly
• Folic acid supplementation is recommended at a dose of 5mg once weekly on the day after the methotrexate

General requirements

• Nurses administering methotrexate should be aware of the principles of good practice in the administration of subcutaneous Methotrexate
• Nurses who are pregnant or breast feeding should not participate in the administration of subcutaneous or intramuscular methotrexate
• Pre-filled syringes should be stored in a locked cupboard at the surgery and at room temperature
• Preparation should take place on a broad edged receiver so that any spillage will be contained. A sink and running water should be readily available

Administration

• An aseptic technique should be used throughout the procedure
• Subcutaneous methotrexate should be administered using the licensed pen device
• There is no need to swab the skin prior to injecting if the skin is socially clean
• There is no need to dispel the small amount of air from a pen device, as it is not harmful to the patient and is rapidly absorbed in the subcutaneous tissues – this will also avoid the risk of splashes/spillage and facilitates the full discharge of contents
• Inject at a 90 degree angle combined with the use of the skin pinch
• Administer the drug into the sub-cutaneous tissues
• There is no need to withdraw prior to injection
• Cover the injection site with spot plaster to prevent leakage onto the skin
• Injection sites should be rotated

Protective equipment

• Latex or PVC gloves
• Plastic apron
• Eye protection is not necessary

• Methotrexate is supplied in a pen device with a needle attached. It is available as a licensed product (Metoject®) in doses of:
• 7.5mg/0.15ml
• 10mg/0.20ml
• 12.5mg/0.25ml
• 15mg/0.30ml
• 17.5mg/0.35ml
• 20mg/0.40ml
• 22.5mg/0.45ml
• 25mg/0.50ml
• 27.5mg/0.55ml
• 30mg/0.60ml
• It should be stored at room temperature (below 25°C) in a safe place
• The first four weeks of treatment will be prescribed by the rheumatology department. Thereafter repeat prescriptions should be continued from the GP surgery.

• Cytotoxic sharps boxes will be supplied by the Rheumatology Nurse Specialist (RNS) at the start of treatment
• Patients should be advised to keep their sharps box in a safe place. It should be sealed when three quarters full and taken to their surgery for disposal. A new box can be supplied on request from RNS.

As for oral methotrexate – please refer to methotrexate DMARD guidelines on Beacon

Please note that in addition to absolute values for haematological indices, a rapid fall or a consistent downward trend in any value should prompt caution and extra vigilance

Nausea

• Ensure patient is on Folic acid, consider increase of folic acid as noted below
• Anti-emetic can be prescribed

Mouth ulcers

• May respond to an increase in folic acid 5mg 3 days/week – can be increased 5mg 6 days/week (not day of methotrexate)

Rash or severe oral ulceration

• Withhold until discussed with rheumatologist
• Consider alternative causes
• Rechallenge with lower dose once symptoms settle

WBC <3.5x109/l

• Withhold until discussed with rheumatologist

Neutrophils <1.6x109/l

• Withhold until discussed with rheumatologist

Platelets <140x109/l

• Withhold until discussed with rheumatologist

AST, ALT >100

• Withhold until discussed with rheumatologist

Albumin – unexplained fall (in absence of active disease) <30g/l

• Withhold until discussed with rheumatologist

Rash or oral ulceration, nausea and vomiting, diarrhoea

• Withhold until discussed with rheumatologist

New or increasing dyspnoea or dry cough

• Withhold and discuss urgently with rheumatologist

MCV >105fl

• Withhold, check serum B12, Folate and TFT & discuss with rheumatologist

Creatinine increase >30% in 12 months

• Withhold and discuss with rheumatologist

Severe sore throat, abnormal bruising

• Immediate FBC and withhold until result available

Alopecia

• Increase in hair loss is common, baldness is rare

Menstrual dysfunction/amenorrhoea

• May occur during treatment and for a short time following cessation

Mild to moderate renal impairment

• Withhold until discussed with rheumatologist (refer to BNF)

Notes:

• One weekly dose of methotrexate can be withheld without inducing a flare
• Methotrexate should not be stopped prior to elective surgery
• Pneumovax (given 2 weeks prior to commencing Metoject) and annual flu vaccinations are recommended

Pregnancy and breastfeeding

• All patients, male and female, should be advised against conception and pregnancy during treatment with methotrexate – it is abortificient and teratogenic
• If patients become pregnant inadvertently, refer to obstetrician
• Breastfeeding should not be allowed as drug may be excreted in breast milk
• Adequate contraception should be continued for at least 3 months after stopping methotrexate

Live vaccines

• Patients taking methotrexate should not have live vaccines
• Possible reduced immunological response to inactivated vaccines

Alcohol

• Advise patients to limit their alcohol intake to well within national recommendations

Chicken pox/shingles

• In patients receiving methotrexate exposed to chicken pox/shingles – withhold methotrexate, check varicella immunoglobulins, in those not previously exposed, immunisation with VZIG should be carried out

Viral respiratory infections

• Treat infection as appropriate
• Continue methotrexate unless symptoms significant

• NSAID’s in addition to the recommended doses of methotrexate are not contraindicated
• Concomitant use of other drugs with anti-folate activities i.e. co-trimoxazole and trimethoprim should be avoided

Refer also to BNF or SPC

Pre treatment assessment by rheumatologist

• FBC, CRP, LFTs, U&Es and hepatitis and HIV serology will be checked prior to commencement
• A baseline chest X-Ray
• Lung function tests may be requested in patients with risk factors or pre-existing lung conditions

Monitoring by GP

• FBC, CRP and LFT’s, U& E’s and albumin every two weeks until dose of methotrexate stable for six weeks, then monthly for 3 months, then 3 monthly
• If possible blood tests should be taken at the trough level, i.e. on the morning before taking the methotrexate
• If a second DMARD is introduced as a combination, then the frequency of monitoring should be increased to the initial starting levels

Patient information leaflet

Patients should be supplied with an information leaflet from the manufacturer

• Shared care assumes communication between the specialist team, GP and patient
• The intention to share care should be explained to the patient and accepted by them
• Patients should be under regular follow-up which provides an opportunity to discuss drug therapy

Rheumatology Consultant

• Pre-treatment assessment and recommendation of the use of sub-cutaneous methotrexate
• Write to the GP enclosing a copy of the NHS Dumfries & Galloway guidelines for the use of subcutaneous methotrexate
• Pre treatment counselling to include rationale for treatment, benefits, potential side effects, precautions and monitoring requirements ensuring patients understand their role in reporting adverse effects promptly
• Issue written patient drug information (arc leaflet), contact telephone number
• Ensure clinical supervision of the patient is done by follow-up as appropriate
• Liaise with GP regarding changes in disease management, drug dose, missed clinic appointments
• Provide telephone support in the event of any serious adverse reactions by a member of the medical team
• Additional support for patients and members of the primary care team, via the rheumatology telephone advice-line
• Provision of formal or informal training by CNS as necessary to ensure that clinical staff within the primary care team have the necessary skills to ensure safe practice

General Practitioner

• Prescribing the sub-cutaneous methotrexate (Metoject) as per the recommendations of the rheumatologist

• Ensure blood tests are taken in accordance with the rheumatology unit information sheets and national guidelines for the monitoring of second line drugs. (BSR 2017) available on the HIPPO system
• Monitor for adverse effects as detailed above
• Check and record blood test results
• Continue repeat prescriptions if blood results satisfactory
• Advise the consultant rheumatologist of any changes in the patient’s condition, any adverse drug reactions, or if the patient fails to attend for blood monitoring
• Ensure that all clinical staff involved in the provision of this service have the relevant knowledge and skills

The patient

• Attend for blood monitoring at requested intervals
• Ensure shared care card is kept up to date
• Report any adverse side effects to medication to the GP or a member of the hospital rheumatology team
• Ensure that they bring an up to date list of all medications to the surgery and out patient consultations

Rheumatology advice Line

• 01387 241095 (answer machine – 9am-12pm Mon-Fri)

Rheumatology nurse specialists

• 01387 246246 Ext 32035/33925/32356 Mon-Fri 8 30am-4

Rheumatology secretary

• 01387 241776  Mon-Fri 8.30am – 5 pm

Rheumatology doctors

• Dr A Russell (lead consultant) 01387 246246 ext 33784
• Dr R Akintayo 01387 246246 ext 33758
• Dr Lucy Moran 01387 241012 Mon-Thurs 2-3pm
• Dr Anne Drever 01387 241023 Mon & Thurs 2-4pm