Common: mild increase in blood pressure
Rare: severe increase in blood pressure
Common: diarrhoea, nausea, vomiting, anorexia, oral mucosal disorders (e.g., aphthous stomatitis, mouth ulceration), abdominal pain
Common: elevation of liver parameters (transaminases [especially ALT], less often gamma-GT, alkaline phosphatase, bilirubin)
Rare: hepatitis, jaundice/cholestasis and very rarely, severe liver injury such as hepatic failure and acute hepatic necrosis that may be fatal
Very rare: pancreatitis
Infections and infestations
Very rare: severe infections, including sepsis which may be fatal
Like other agents with immunosuppressive potential, leflunomide may increase susceptibility to infections, including opportunistic infections (see also section 4.4). Thus, the overall incidence of infections can increase (in particular of rhinitis, bronchitis and pneumonia)
Metabolism and nutrition disorders
Common: weight loss (usually insignificant)
Nervous system disorders
Common: headache, dizziness, asthenia, paraesthesia
Uncommon: taste disturbances, anxiety
Very rare: peripheral neuropathy
Musculoskeletal and connective tissue disorders
Uncommon: tendon rupture
Skin and subcutaneous tissue disorders
Common: increased hair loss, eczema, dry skin
Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme
Immune system disorders
Common: mild allergic reactions, rash (including maculopapular rash), pruritus
Very rare: severe anaphylactic/anaphylactoid reactions
Respiratory, thoracic and mediastinal disorders
Rare: interstitial lung disease (including interstitial pneumonitis), which may be fatal.
Blood and lymphatic system disorders
Common: leukopenia (leukocytes>2 G/l)
Uncommon: anaemia, mild thrombocytopenia (platelets <100 G/l)
Rare: eosinophilia, leukopenia (leukocytes <2 G/l), pancytopenia (probably by antiproliferative mechanism)
Very rare: agranulocytosis, vasculitis
Recent, concomitant or consecutive use of potentially myelotoxic agents may be associated with a higher risk of haematological effects.
The risk of malignancy, particularly lymphoproliferative disorders, is increased with use of some immunosuppressive agents.
Mild hyperlipidaemia may occur. Uric acid levels usually decrease.
Laboratory findings for which a clinical relevance could not be established include small increases in LDH and CK. Mild hypophosphataemia is uncommon.
Marginal (reversible) decreases in sperm concentration, total sperm count and rapid progressive motility cannot be excluded.
The active metabolite of leflunomide, A771726, has a long half-life, usually 1 to 4 weeks. If a severe undesirable effect of leflunomide occurs, or if for any other reason A771726 needs to be cleared rapidly from the body, the washout procedure described in section 4.4 has to be followed. The procedure may be repeated as clinically necessary. For suspected severe immunological/allergic reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, a complete washout is essential.