Leflunomide therapeutics (Drugs used in immune diseases) Flashcards
What drug class does leflunomide belong to?
Is a DMARD- disease-modifying anti-rheumatic drug
What two conditions is leflunomide indicated for?
- Rheumatoid arthritis
- Psoriatic arthritis
What is the typical leflunomide dose for RA patients?
Initially 100 mg once daily for 3 days (Loading dose), then reduced to 10–20 mg once daily
What is the typical leflunomide dose for psoriatic arthritis patients?
Initially 100 mg once daily for 3 days, then reduced to 20 mg once daily
Does leflunomide exert its effect immediately?
- No, it takes 4-6 weeks to start having an effect and can increase for 4-6 months
What monitoring should be carried out on patients taking Leflunomide and when?
- Liver function test (LFTs)
- Full blood count
- Blood pressure
- Pregnancy test- pregnancy should be excluded
Should be carried out prior to initiating treatment, then every 2 weeks for 6 months, then every 8 weeks thereafter.
When/how frequently should patients be monitored while on leflunomide?
Should be carried out prior to initiating treatment, then every 2 weeks for 6 months, then every 8 weeks thereafter.
What are the side effects of taking leflunomide?
- hepatic impairment- risk is increased when used with other hepatotoxic drugs. Most often occurs within the first 6 months hence the increased frequency of monitoring within this period.
- Bone marrow suppression- leucopenia, anaemia, thrombocytopaenia, increased infection risk
- Increased blood pressure - common
common side effects: GI pain, diarrhoea, alopecia, skin reactions (rash, itchiness), Dizziness, cough
When is leflunomide contra-indicated?
- Hepatic impairment- there is a risk of accumulation of the drug as it is partially metabolised in the liver
- Severe immunodeficiency- would further decrease the immune response
- Severe infection- decreased ability of the immune system to fight any infection
- Hypoproteinemia- the drug is highly protein-bound and so this would increase plasma levels (?)
- Moderate-severe renal impairement
- pregnancy and breastfeeding- the active metabolite is teratogenic- females should use contraception during + 2 years after treatment and 3 months after in men
What contraception is required in patients who take/have taken leflunomide and why?
The active metabolite of the drug is teratogenic so females should use effective contraception while on leflunomide and for 2 years after stopping and males while on leflunomide and for 3 months after stopping.
When is leflunomide cautioned?
- Patients already taken haemotoxic or hepatotoxic drugs- have similar side effects and increased risk of toxicity
- In pts with a history of tuberculosis as it can cause reactivation of the disease
- Patients who already have bone marrow suppression
Why may the effects of Leflunomide be seen even after cessation?
Because leflunomide has a long half-life- 1-4 weeks and so can continue to exert its effect as the drug isn’t fully cleared until after 5 half-lives.
How many half-lives does it take for leflunomide to be fully cleared from the body?
5
How long is its half-life?
1-4 weeks
What needs to be done should a patient have a severe adverse reaction to the drug? (or wants to conceive, or swap to another treatment)
The patient needs to have a ‘Wash out procedure’ in order to remove the active metabolite from their system:
- Stop leflunomide
- Give Colestyramine 8mg TDS or activated charcoal 50mg QDS for 11 days
- Monitor for leflunomide levels
