Summary of the safety profile The most common and most important adverse reactions reported for diflunisal are gastro-intestinal. Tabulated list of adverse reactions Adverse reactions are listed below by MedDRA System Organ Class (SOC) and frequency categories using the standard convention: 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) and Not known (frequency cannot be estimated from the available data).
Table 1 Tabulated list of adverse reactions System Organ Class Very common Common Uncommon Very rare Infections and infestations Viral gastroenteritis Blood and lymphatic system disorders Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia, haemolytic anaemia 8 System Organ Class Very common Common Uncommon Very rare Immune system disorders Acute anaphylactic reaction with bronchospasm, angioedema, hypersensitivity vasculitis, hypersensitivity syndrome Psychiatric disorders Depression, hallucinations, nervousness, confusion Nervous system disorders Headache, dizziness, somnolence, insomnia Vertigo, light headedness, paraesthesiae Eye disorders Ocular hypertension Transient visual disturbances including blurred vision Ear and labyrinth disorders Tinnitus Cardiac disorders Cardiac failure Palpitations, syncope Vascular disorders Hypertension Allergic vasculitis Respiratory, thoracic and mediastinal disorders Dyspnoea Rhinitis, asthma Gastrointestinal disorders Dyspepsia Gastrointestinal pain, diarrhoea, nausea, vomiting, constipation, flatulence, gastrointestinal perforation and bleeding, gastroesophageal reflux disease Peptic ulcer, anorexia, gastritis, haematemesis, melaena, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease Hepatobiliary disorders Jaundice sometimes with fever, cholestasis, liver- function abnormality, hepatitis Raised transaminases Skin and subcutaneous tissue disorders Rash, sweating, dermatitis, erythema Pruritus, dry mucous membranes, stomatitis, photosensitivity, urticaria, erythema multiforme, Stevens Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis Musculoskeletal and connective tissue disorders Muscle cramps Renal and urinary disorders Renal failure, proteinuria Dysuria, renal impairment, interstitial nephritis, haematuria, nephritic syndrome 9 System Organ Class Very common Common Uncommon Very rare General disorders and administration site conditions Fatigue, oedema, peripheral oedema, chest pain, early satiety, Asthenia, loss of apetite Investigations Occult blood positive, haematocrit decreased An apparent hypersensitivity syndrome has been reported in a few patients treated with diflunisal.
This syndrome manifests the following symptoms: fever, chills, cutaneous reactions of different severity, changes in liver function, jaundice, leucopenia, thrombocytopenia, eosinophilia, disseminated intravascular coagulation, renal impairment, adenitis, arthralgia, myalgia, arthritis, anorexia, disorientation.
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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.