Rheumatology pharmacology

Question 1

what does DMARD stand for?

Answer 1

disease modifying anti-rheumatic drugs

Question 2

what are the most commonly prescribed DMARDs?

Answer 2

methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide

Question 3

what is a less commonly prescribed DMARD?

Answer 3

azathioprine

Question 4

how does methotrexate cause immunosuppression?

Answer 4

competitive inhibitor for dihydrofolate reductase enzyme, inhibiting the reduction of dihydrofolate to tetrahydrofolate (active form)

Question 5

what are the clinical indications for methotrexate?

Answer 5

Rheumatoid arthritis
Malignant disease – used as an anti-metabolite in cancer therapy
Crohn’s disease

Question 6

how is methatrexate prescribed?

Answer 6

Rheumatology: dose range 5-25mg once weekly
Gastroenterology: Starting dose – 25mg once weekly for 16 weeks, Maintenance dose – 15mg once weekly
Always prescribe methotrexate in multiples of the 2.5mg tablet strength

Question 7

what are the adverse effects for methotrexate?

Answer 7

Common:
Nausea, diarrhoea
Alopecia
Stomatitis – stop treatment if this occurs, mucositis
Important:
Myelosuppression including leucopenia and neutropenia
Hepatotoxicity
Pulmonary fibrosis, interstitial pneumonitis
Pericarditis, pericardial tamponade

Question 8

what are the contraindications for methotrexate prescription?

Answer 8

Caution in ulcerative colitis, peptic ulcer disease and ulcerative stomatitis
Avoid in pregnancy and breastfeeding, severe hepatic or renal impairment, blood disorders
(severe anaemia, leucopenia or thrombocytopenia), untreated folate deficiency and history
of alcohol abuse/cirrhosis
Hold methotrexate temporarily if patient is systemically unwell with significant infection
requiring anti-infective intervention

Question 9

what are the drug interactions of methotrexate?

Answer 9

Trimethoprim/co-trimoxazole (risk of pancytopenia, do not co-prescribe)
NSAIDs (may reduce methotrexate excretion but unlikely to cause clinically significant
adverse effects, concomitant use common in rheumatic disease)
Clozapine (increased risk of agranulocytosis – avoid concomitant use)
Acitretin (increased plasma methotrexate concentration, increased risk of hepatotoxicity –
avoid concomitant use)
Live vaccines (high risk of infection due to immunosuppressive effect of methotrexate)

Question 10

how is methotrexate be monitored?

Answer 10

Baseline tests should include FBC, U&E, LFT, ESR and CRP. Selected patients may require
pulmonary function testing and CXR. FBC, U&E and LFT should be checked every 1-2 weeks until
patient is stabilised and then every 2-3 months thereafter (monthly in rheumatology). ESR and CRP
should be re-checked avery 3 months.
Also ask about oral ulceration/sore throat, unexplained rash or unusual bruising at every
consultation.

Question 11

what should patients be told when starting on methotrexate?

Answer 11

Explain to female patients that they must not take this medication during pregnancy. Both men and
women should be advised to use reliable contraception throughout treatment and for 3 months
after stopping methotrexate. If a patient or their partner does become pregnant while on
methotrexate they should inform their doctor immediately and the medication should be stopped.
Patients should be advised to avoid taking NSAIDs unless prescribed by their doctor.
Advise patients that they should immediately report to their doctor any features of blood disorder
(sore throat, bruising, mouth ulcers), liver toxicity (nausea, vomiting, abdominal discomfort, dark
urine) or respiratory effects e.g. shortness of breath