Febustad 80 Adverse Reactions

Summary of the safety profile: The most commonly reported adverse reactions in clinical trials (4,072 subjects treated at least with a dose from 10 mg to 300 mg), post-authorisation safety studies (FAST study: 3,001 subjects treated at least with a dose from 80 mg to 120 mg) and post-marketing experience are gout flares, liver function abnormalities, diarrhoea, nausea, headache, dizziness, dyspnoea, rash, pruritus, arthralgia, myalgia, pain in extremity, oedema and fatigue. These adverse reactions were mostly mild or moderate in severity. Rare serious hypersensitivity reactions to febuxostat, some of which were associated to systemic symptoms, and rare events of sudden cardiac death, have occurred in the post-marketing experience.
Tabulated list of adverse reactions: Common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and rare (≥1/10,000 to <1/1,000) adverse reactions occurring in patients treated with febuxostat are listed as follows.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Blood and lymphatic system disorders: Rare: Pancytopenia, thrombocytopenia, agranulocytosis*, anaemia^#.
Immune system disorders: Rare: Anaphylactic reaction*, drug hypersensitivity*.
Endocrine disorders: Uncommon: Blood thyroid stimulating hormone increased, hypothyroidism^#.
Eye disorders: Uncommon: Blurred vision.
Rare: Retinal artery occlusion^#.
Metabolism and nutrition disorders: Common: Gout flares.
Uncommon: Diabetes mellitus, hyperlipidaemia, decrease appetite, weight increase.
Rare: Weight decrease, increase appetite, anorexia.
Psychiatric disorders: Uncommon: Libido decreased, insomnia.
Rare: Nervousness, depressed mood^#, sleep disorder^#.
Nervous system disorders: Common: Headache, dizziness.
Uncommon: Paraesthesia, hemiparesis, somnolence, lethargy^#, altered taste, hypoaesthesia, hyposmia.
Rare: Ageusia^#, burning sensation^#.
Ear and labyrinth disorders: Uncommon: Tinnitus.
Rare: Vertigo^#.
Cardiac disorders: Uncommon: Atrial fibrillation, palpitations, ECG abnormal, arrhythmia^#.
Rare: Sudden cardiac death*.
Vascular disorders: Uncommon: Hypertension, flushing, hot flush.
Rare: Circulatory collapse^#.
Respiratory system disorders: Common: Dyspnoea.
Uncommon: Bronchitis, upper respiratory tract infection, lower respiratory tract infection^#, cough, rhinorrhoea^#.
Rare: Pneumonia^#.
Gastrointestinal disorders: Common: Diarrhoea**, nausea.
Uncommon: Abdominal pain, abdominal pain upper^#, abdominal distension, gastrooesophageal reflux disease, vomiting, dry mouth, dyspepsia, constipation, frequent stools, flatulence, gastrointestinal discomfort, mouth ulceration, lip swelling^#, pancreatitis.
Rare: Gastrointestinal perforation^#, stomatitis^#.
Hepatobiliary disorders: Common: Liver function abnormalities**.
Uncommon: Cholelithiasis.
Rare: Hepatitis, jaundice*, liver injury*, cholecystitis^#.
Skin and subcutaneous tissue disorders: Common: Rash (including various types of rash reported with lower frequencies, see as follows), pruritus.
Uncommon: Dermatitis, urticaria, skin discolouration, skin lesion, petechiae, rash macular, rash maculopapular, rash papular, hyperhidrosis, alopecia, eczema^#, erythema, night sweats^#, psoriasis^#, rash pruritic^#.
Rare: Toxic epidermal necrolysis*, Stevens-Johnson Syndrome*, angioedema*, drug reaction with eosinophilia and systemic symptoms*, generalized rash (serious)*, exfoliative rash, rash follicular, rash vesicular, rash pustular, rash erythematous, rash morbilliform.
Musculoskeletal and connective tissue disorders: Common: Arthralgia, myalgia, pain in extremity^#.
Uncommon: Arthritis, musculoskeletal pain, muscle weakness, muscle spasm, muscle tightness, bursitis, joint swelling^#, back pain^#, musculoskeletal stiffness^#, joint stiffness.
Rare: Rhabdomyolysis*, rotator cuff syndrome^#, polymyalgia rheumatica^#.
Renal and urinary disorders: Uncommon: Renal failure, nephrolithiasis, haematuria, pollakiuria, proteinuria, micturition urgency, urinary tract infection^#.
Rare: Tubulointerstitial nephritis*.
Reproductive system and breast disorders: Uncommon: Erectile dysfunction.
General disorders and administration site conditions: Common: Oedema, fatigue.
Uncommon: Chest pain, chest discomfort, pain^#, malaise^#.
Rare: Thirst, feeling hot^#.
Investigations: Uncommon: Blood amylase increase, platelet count decrease, WBC decrease, lymphocyte count decrease, blood creatine increase, blood creatinine increase, haemoglobin decrease, blood urea increase, blood triglycerides increase, blood cholesterol increase, haematocritic decrease, blood lactate dehydrogenase increased, blood potassium increase, INR increased^#.
Rare: Blood glucose increase, activated partial thromboplastin time prolonged, red blood cell count decrease, blood alkaline phosphatase increase, blood creatine phosphokinase increase*.
Injury, poisoning and procedural complications: Uncommon: Contusion^#.
* Adverse reactions coming from post-marketing experience.
** Treatment-emergent non-infective diarrhoea and abnormal liver function tests in the combined Phase 3 studies are more frequent in patients concomitantly treated with colchicine.
^# Adverse reactions coming from post-authorisation safety studies.
Description of selected adverse reactions: Rare serious hypersensitivity reactions to febuxostat, including Stevens-Johnson syndrome, toxic epidermal necrolysis and anaphylactic reaction/shock, have occurred in the post-marketing experience. Stevens-Johnson syndrome and toxic epidermal necrolysis are characterised by progressive skin rashes associated with blisters or mucosal lesions and eye irritation. Hypersensitivity reactions to febuxostat can be associated to the following symptoms: skin reactions characterised by infiltrated maculopapular eruption, generalised or exfoliative rashes, but also skin lesions, facial oedema, fever, haematologic abnormalities such as thrombocytopenia and eosinophilia, and single or multiple organ involvement (liver and kidney including tubulointerstitial nephritis).
Gout flares were commonly observed soon after the start of treatment and during the first months. Thereafter, the frequency of gout flare decreases in a time-dependent manner. Gout flare prophylaxis is recommended.