Methotrexate Therapeutics

Question 1

What diseases are low dose methotrexate used to treat?

Answer 1

Immune diseases such as:
- Rheumatoid arthiritis
- Psoriasis
- Inflammatory bowel disease

Question 2

What is high dose methotrexate used for?

Answer 2

Cancer chemotherapy regimes

Question 3

In what formulations is low dose methotrexate available in?

Answer 3

• Oral (PO)
• Intramuscular (IM)
• Subcutaneous (SC)

There are slight differences in dosing for different immune diseases and when using different routes

Question 4

What is the frequency of administration for low dose Methotrexate?

Answer 4

ONCE A WEEK
- On the same day of the week
- Dose and frequency should be clear on the label

Question 5

Why are patients given a ‘test dose’ prior to starting low dose methotrexate therapy?

Answer 5

It is advisable for patients to receive a test dose in order to rule out idiosyncratic adverse effects that may occur from the methotrexate.

• Usually a 2.5mg tablet as a single dose one off and the patient monitors any signs of adverse effects associated with that.

Question 6

What strength tablets are used for low dose methotrexate?

Answer 6

The strength of tablet should be prescribed as a single strength of tablet, only 2.5mg should be used

Question 7

How long does the low dose methotrexate take to have its effect?

Answer 7

Generally it will take some time for methotrexate to start to have its effect and for that effect to be at a maximum.

• I.e. for RA it can take up to 6 week to begin to work and 12 weeks to feel the maximum effect
• Important that patient is aware of this so that they continue taking their medication

Question 8

In RA, dose escalation is required to reach the optimal dose. How is this achieved?

Answer 8

2.5mg - 5mg increases every 1-3 weeks

• Should aim for optimal dose in 4-6 weeks of administration

Question 9

Before starting therapy, what baseline assessments should be carried out?

Answer 9

• Full blood count (FBC)
• Liver function tests (LFT)
• Urea and electrolyte (U&E)
• Renal function (creatinine, CR or estimated eGFR)
• Chest X-Ray

This allows effects due to methotrexate on the patient, to be monitored during their therapy with low dose methotrexate.

Question 10

What motioning is done during their low dose methotrexate therapy?

Answer 10

LFTs
Renal function
Full blood count (FBC)

• Monitored every 1-2 weeks until therapy is stabilised
• Once therapy is stabilised the every 2-3 months

Monitoring will be stepped up if there are any abnormalities seen

Question 11

Patients and carers also have a responsibility for self monitoring. How can patients or carers do this?

Answer 11

1. Look out for any signs of an infections I.e. sore throat, bruising, bleeding - Indicating blood disorders
2. Nausea, vomiting, abdominal discomfort and dark urine - Indicating liver toxicity
3. Shortness of breath - Indicating respiratory effects

These are things healthcare professionals will not know, unless patients tells us.

Question 12

What are the key side effects of taking low dose methotrexate?

Answer 12

Common:
- Sickness
- Nausea
- Diarrhoea
Generally this settles down, but if not can increase the dose of folic acid

Patient may suffer with mouth ulcers or sore throat/mouth and it is important to check the patients blood tests to check whether the methotrexate is having an massive adverse effect on the patients FBC which is a sign of toxicity:
- Generally this settles down, but if not can increase the dose of folic acid

Key signs of toxicity:
- Bone marrow suppression
- GI toxicity
- Lover toxicity
- Pulmonary toxicity
- Skin reactions

Question 13

What are the key contraindications for low dose methotrexate

Answer 13

• An active infection (won’t be able to fight infection effectively due to bone marrow suppression)
• Severe renal impairment (as its mainly renally eliminated)
• Hepatic impairment (hepatotoxicity)
• Bone marrow suppression
• Immunodeficiency
• Pregnancy and breast feeding (should use effective contraception, and 3-6months after stopping therapy)

Question 14

What is methotrexate co prescribed with?

Answer 14

Folic acid

Dose: Folic acid 5mg OD (1-6 days a week, NOT METHOTREXATE DAY)

This is taken alongside methotrexate because methotrexate is an antifolate medication and some of the side effects seen are associated with that anti folate effect. Folic acid helps to reduce the adverse effects such as hepatotoxicity and GI side effects.

Question 15

What are the key cautions to consider when prescribing low dose methotrexate?

Answer 15

1. Surgery
   - Patients that are due to have surgery will often stop their methotrexate before they have surgery, due to the effects on bone marrow with the potential of increasing the patients risk of infection
2. Renal impairment
   - Dose may be reduced according to the degree of the patients renal impairment and extra monitoring is also required
3. Diarrhoea + Vomiting
   (causes dehydration hence increasing the risk of renal impairment)
4. Ascites
   (a condition in which fluid collects in spaces within your abdomen)
   - Methotrexate will accumulate/build up in that fluid, which will lead to accumulation of that drug in the patient
5. Peptic ulcer
   - Due to risk of GI toxicity
6. Elderly patients
   - Due to their natural reduced folates and naturally reduced renal impairment and hepatic impairment
7. Patients who have NEVER had chickenpox
   - Should contact the doctor if they come into contact with someone with chickenpox or shingles as this would need to be treated as their at risk of getting severe infections.

• They may have their methotrexate paused or stopped for a period of time until the infection is cleared/improved. This is to improve the body’s ability to fight the infection

Question 16

What is important to consider about the amount to supply of methotrexate?

Answer 16

Supply only the required amount of methotrexate and folic acid.

• This helps to reduce the risk of inadvertent administration

Question 17

What can be done if you miss a dose of methotrexate?

Answer 17

Doses can be taken within 2 days of their regular day

e.g. If they normally take it on Monday, they can take it up to Wednesday. If they go beyond Wednesday, they should MISS that methotrexate dose. The following week they should return back to taking it on Monday.

Question 18

What are the interactions associated with Methotrexate?

Answer 18

• Anti-folates -> Co-trimoxazole, trimethoprim (can increase the anti-folate effect of methotrexate hence leading to toxicity)
• NSAIDs (reduces the release of methotrexate via the kidneys, but can be taken if monitored carefully but patients cant self prescribe NSAIDs)
• Live vaccines (less likely to work as well as they rely on the immune response and have potential to cause infection)
• Ciclosporin (increases methotrexate toxicity)
• Any other drugs that are hepatotoxic, heamatotoxic or nephrotoxic

Question 19

What vaccines are recommended for patients on Methotrexate?

Answer 19

Pneumococcal (one off vaccine) and influenza (yearly) vaccine to reduce the risk of getting these infections.

Question 20

What counselling points should be given to patients taking methotrexate?

Answer 20

• Inform all healthcare professionals that they use methotrexate
• Methotrexate is NOT a painkiller
• Time of action, the dose, strength and frequency of the use of Methotrexate is highlighted
• Patients are aware of signs and symptoms they should be self monitoring
• Patients need to aware of why were carrying out multiple blood tests when on methotrexate and importance
• Aware of common side effects and they should resolve if not its a sign of toxicity
• Always carry your methotrexate card
• Should obtain a monitoring booklet
• If you take too many methotrexate, they need to seek help IMMEDIATELY
• Alcohol consumption -> Alcohol affects a patients liver and liver toxicity is an adverse effect associated with Methotrexate. Using alcohol with methotrexate, were increasing the risk of liver damage.
  Occasional drink of alcohol is fine but not using the recommended daily allowance everyday
• Avoid self prescribing NSAIDs