Summary of the safety profile: In clinical trials, etoricoxib was evaluated for safety in 9,295 individuals, including 6,757 patients with OA, RA, chronic low back pain or ankylosing spondylitis (approximately 600 patients with OA or RA were treated for one year or longer).
In a cardiovascular safety outcomes program of pooled data from three active comparator controlled trials, 17, 412 patients with OA or RA were treated with etoricoxib (60 mg or 90 mg) for a mean duration of approximately 18 months. The safety data and details from this program are presented in Pharmacology: Pharmacodynamics under Actions.
In clinical studies the following undesirable effects were reported at an incidence greater than placebo in patients with OA, RA, chronic low back pain or ankylosing spondylitis treated with etoricoxib 30 mg, 60 mg or 90 mg for up to 12 weeks or in the MEDAL Program studies.
[Common (≥1/100, <1/10), Uncommon (≥1/1000, <1/100), Rare (≥1/10,000, <1/1,000), Very rare (<1/10,000), not known (cannot be estimated from the available data)].
Infections and infestations: Uncommon: gastro-enteritis, upper respiratory infection, urinary tract infection.
Immune system disorder: Very rare: drug hypersensitivity.
Metabolism and nutrition disorders: Common: oedema/fluid retention.
Uncommon: appetite increase or decrease, weight gain.
Psychiatric disorders: Uncommon: anxiety, depression, mental acuity decreased.
Nervous system disorder: Common: dizziness, headache.
Uncommon: dysgeusia, insomnia, paraesthesia/hypaesthesia, somnolence.
Eye disorders: Uncommon: blurred vision.
Ear and labyrinth disorders: Uncommon: tinnitus.
Cardiac disorders: Uncommon: atrial fibrillation, congestive heart failure, non-specific ECG changes.
Very rare: myocardial infarction.
Vascular disorders: Common: hypertension.
Very rare: cerebrovascular accident.
Respiratory, thoracic and mediastinal disorders: Uncommon: cough, dyspnoea, epistaxis.
Gastro-intestinal disorders: Common: gastro-intestinal disorders (e.g. abdominal pain, flatulence, heartburn), diarrhoea, dyspepsia, epigastric discomfort, nausea.
Uncommon: abdominal distention, acid reflux, bowel movement pattern change, constipation, dry mouth, gastroduodenal ulcer, irritable bowel syndrome, oesophagitis, oral ulcer, vomiting, gastritis.
Very Rare: gastro-intestinal perforation and bleeding.
Skin and subcutaneous tissue disorders: Uncommon: ecchymosis, facial oedema, pruritus, rash.
Musculoskeletal, connective tissue and bone disorders: Uncommon: muscular cramp/spasm, musculoskeletal pain/stiffness.
Renal and urinary disorders: Uncommon: proteinuria.
General disorders and administration site conditions: Common: asthenia/fatigue, flu-like disease.
Uncommon: chest pain.
Investigations: Common: ALT increased, AST increased.
Uncommon: blood urea nitrogen increased, creatine phosphokinase increased, haematocrit decreased, haemoglobin decreased, hyperkalaemia, leukocytes decreased, platelets decreased, serum creatinine increased, uric acid increased.
In clinical studies, the undesirable effects profile was similar in patients with OA or RA treated with etoricoxib for one year or longer.
In a combined analysis of phase IIb to V clinical studies of 4 weeks duration or longer (excluding the MEDAL Program Studies), there was no discernible difference in the rate of confirmed thrombotic cardiovascular serious adverse events between patients receiving etoricoxib ≥ 30 mg or non-naproxen NSAIDs. The rate of these events was higher in patients receiving etoricoxib compared with those receiving naproxen 500 mg twice daily.
In a clinical study for ankylosing spondylitis, patients were treated with Etoricoxib 90 mg once daily for up to 1 year (N=126). In another clinical study for ankylosing spondylitis (N=857), patients were treated with Etoricoxib 60 mg or 90 mg once daily for up to 26 weeks. The adverse experience profile in these studies was generally similar to that reported in chronic studies in OA, RA and chronic low back pain.
In a clinical study for acute gouty arthritis, patients were treated with etoricoxib 120 mg once daily for eight days. The adverse experience profile in this study was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.
In initial clinical studies for acute analgesia, patients were treated with Etoricoxib 120 mg once daily for one to seven days. The adverse experience profile in these studies was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.
In additional clinical studies for acute post-operative pain including 1222 patients treated with Etoricoxib (90 mg or 120 mg), the adverse experience profile was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.
In the combined studies for acute post-operative dental pain, the incidence of post-dental extraction alveolitis (dry socket) reported in patients treated with Etoricoxib was similar to that of patients treated with active comparators.
The following serious undesirable effects have been reported in association with the use of NSAIDs and cannot be ruled out for etoricoxib: nephrotoxicity including interstitial nephritis and nephrotic syndrome; hepatotoxicity including hepatic failure and pancreatitis.
Post-marketing experience: The following adverse reactions have been reported in post-marketing experience: Blood and lymphatic system disorders: thrombocytopenia.
Immune system disorders: hypersensitivity reactions, anaphylactic/anaphylactoid reactions, including shock.
Metabolism and nutrition disorders: hyperkalemia.
Psychiatric disorders: anxiety, insomnia, confusion, hallucinations, depression, restlessness.
Nervous system disorders: dysgeusia, somnolence.
Cardiac disorders: congestive heart failure, palpitations, angina, arrhythmia.
Vascular disorders: hypertensive crisis.
Respiratory, thoracic and mediastinal disorders: bronchospasm.
Gastrointestinal disorders: abdominal pain, oral ulcers, peptic ulcers including perforation and bleeding (mainly in elderly patients), vomiting, diarrhea.
Hepatobiliary disorders: hepatitis, jaundice, hepatic failure.
Skin and subcutaneous tissue disorders: angioedema, pruritus, erythema, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, fixed drug eruption.
Renal and urinary disorders: renal insufficiency, including renal failure (see Precautions).