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
How long does the ‘washout’ procedure for leflunomide need to be taken for?
11 days
What drug and dose is given for the ‘washout procedure’ to eliminate leflunomide from the body?
Cholestyramine 8mg TDS for 11 days
OR
Activated charcoal 50mg QDS for 11 days
