Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile

The most frequently reported adverse effects with leflunomide are: mild increase in blood pressure, leucopenia, paraesthesia, headache, dizziness, diarrhoea, nausea, vomiting, oral mucosal disorders (e.g. aphthous stomatitis, mouth ulceration), abdominal pain, increased hair loss, eczema, rash (including maculo-papular rash), pruritus, dry skin, tenosynovitis, CPK increased, anorexia, weight loss (usually insignificant), asthenia, mild allergic reactions and elevation of liver parameters (transaminases (especially ALT), less often gamma-GT, alkaline phosphatise, bilirubin)).

Classification of expected frequencies:
Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Infections and infestations
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).
Neoplasms benign, malignant and unspecified (incl. cysts and polyps)
The risk of malignancy, particularly lymphoproliferative disorders, is increased with use of some immunosuppressive agents.
Blood and lymphatic system disorders
Common:              leucopenia (leucocytes >2 G/L)
Uncommon:            anaemia, mild thrombocytopenia (platelets <100 G/L) Rare:                pancytopenia (probably by antiproliferative mechanism), leucopenia (leucocytes <2 G/L), eosinophilia
Very rare:           agranulocytosis
Recent, concomitant or consecutive use of potentially myelotoxic agents may be associated with a higher risk of haematological effects.
Immune system disorders
Common:              mild allergic reactions
Very rare:           severe anaphylactic/anaphylactoid reactions, vasculitis, including cutaneous necrotizing vasculitis

Metabolism and nutrition disorders
Common:              CPK increased
Uncommon:            hypokalaemia, hyperlipidemia, hypophosphataemia
Rare:                LDH increased
Not known:           hypouricemia
Psychiatric disorders
Uncommon:            anxiety

Nervous system disorders
Common:              paraesthesia, headache, dizziness, peripheral neuropathy Cardiac disorders
Common:              mild increase in blood pressure
Rare:                severe increase in blood pressure
Respiratory, thoracic and mediastinal disorders
Rare:                interstitial lung disease (including interstitial pneumonitis), which may be fatal 
Not known:             pulmonary hypertension

Gastrointestinal disorders
Common:                colitis including microscopic colitis such as lymphocytic colitis, collagenous colitis, diarrhoea, nausea, vomiting, oral mucosal disorders (e.g., aphthous stomatitis, mouth ulceration), abdominal pain,
Uncommon:              taste disturbances
Very rare:             pancreatitis
Hepatobiliary disorders
Common:                elevation of liver parameters (transaminases [especially ALT], less often gamma-GT, alkaline phosphatase, bilirubin)
Rare:                  hepatitis, jaundice/cholestasis
Very rare:             severe liver injury such as hepatic failure and acute hepatic necrosis that may be fatal
Skin and subcutaneous tissue disorders
Common:                increased hair loss, eczema, rash (including maculopapular rash), pruritus, dry skin
Uncommon:              urticaria
Very rare:             toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme Not known:             cutaneous lupus erythematosus, pustular psoriasis or worsening psoriasis, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), skin ulcer.
Musculoskeletal and connective tissue disorders
Common:                tenosynovitis
Uncommon:              tendon rupture
Renal and urinary disorders
Not known:             renal failure
Reproductive system and breast disorders
Not known:             marginal (reversible) decreases in sperm concentration, total sperm count and rapid progressive motility

General disorders and administration site conditions
Common:                anorexia, weight loss (usually insignificant), asthenia 
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form at https://sideeffects.health.gov.il/.