Teriflunomide

Basic information
Derivative of Leflunomide – used in RA Once a day, oral 14mg (there is a 7mg dose use?); taken any time day

Side effects
Generally well tolerated Side-effects: GI, low WBC, liver toxicity

Common Side effects (2-10%)– headache, nausea, diarrhoea, hair thinning, LFTs

Contra-indications: cytopaenias, serious infection; caution in previous TB, persistent cough, 'substantial' alcohol use

TB screening beforehand, but risk of infections low

Can push up BP (a bit) 1% peripheral neuropathy esp in diabetics

Efficacy
1st line oral DMT = Rebif 44 (in clinical trials) Efficacy: ARR 40% for any relapse (‘relapse-free survival’) after 1 year, 20% after 2 years, in RRMS (Cochrane 2016; all trials high risk of conflict of interest)

Monitoring
Company nurse monitoring for 6/12; community MS nurse thereafter Annual consultant review LFTs monitored 2 weekly for first 6/12; then 2 monthly
 * If LFTs > 2x ULN, then weekly bloods
 * If LFTs > 3x ULN then stop

Can cause drop in WCC (consider stopping if Neutrophils < 1.5, or lymp <0.8) usually noted in first 6/52 and may persist

Family planning
Absolute CI pregnancy – teratogenic ++ in animal data Breast feeding not known to be safe It is excreted in semen, men should not father children on it Accelerated elimination if want family

Accelerated elimination
Can hang around for >1 year (biliary excretion and gut reabsorption) Accelerated elimination (11 days activated charcoal or cholestyramine to get level <0.02mg/ml)

Interactions
No live vaccinations CYP1A2 Interactions +++ Increased risk of statin toxicity (esp Rosuvastatin) Interactions with Pioglitazone, Warfarin Reduces Duloxetine, Tizanidine, Theophyline Increases oestrogen (OCP?) Beware use with other hepatotoxic drugs

Accelerated elimination for rising LFTs, Stevens Johnson/severe skin reactions

Post marketing
Pancreatitis, low platelets, Angioedema

Links

 * BNF entry
 * Summary of Product Characteristics (SmPC)
 * Cochrane review 2016