Adverse reactions : תופעות לוואי

4.8 Undesirable effects

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 clinical studies, the undesirable effects profile was similar in patients with OA or RA treated with etoricoxib for one year or longer.

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 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 section 5.1.

In clinical studies for acute postoperative dental pain following surgery including 614 patients treated with etoricoxib (90 mg or 120 mg), the adverse experience profile in these studies was generally similar to that reported in the combined OA, RA, and chronic low back pain studies.

Tabulated list of adverse reactions
The following undesirable effects were reported at an incidence greater than placebo in clinical trials in patients with OA, RA chronic low back pain or ankylosing spondylitis treated with etoricoxib 30 mg, 60 mg or 90 mg up to the recommended dose for up to 12 weeks; in the MEDAL Program studies for up to 3½ years; in short term acute pain studies for up to 7 days; or in post-marketing experience (see Table 1):
Table 1:
System Organ Class                    Adverse Reactions                   Frequency Category* Infections and infestations           alveolar osteitis                   Common gastroenteritis, upper respiratory  Uncommon infection, urinary tract infection
Blood and lymphatic system anaemia (primarily associated with Uncommon disorders                             gastrointestinal bleeding),
leukopenia, thrombocytopenia
Immune system disorders               hypersensitivity‡ ß                 Uncommon angioedema/anaphylactic             Rare
                                        /anaphylactoid reactions including shock‡
Metabolism and nutrition      oedema/fluid retention                 Common disorders appetite increase or decrease,         Uncommon weight gain
Psychiatric disorders         anxiety, depression, mental acuity     Uncommon decreased, hallucinations‡ confusion‡, restlessness‡              Rare
Nervous system disorders      dizziness, headache                    Common dysgeusia, insomnia,                   Uncommon paresthaesia/hypaesthesia,
somnolence
Eye disorders                 blurred vision, conjunctivitis         Uncommon Ear and labyrinth disorders   tinnitus, vertigo                      Uncommon Cardiac disorders             palpitations, arrhythmia‡              Common atrial fibrillation, tachycardia‡,     Uncommon congestive heart failure, non- specific ECG changes, angina pectoris‡, myocardial infarction§
Vascular disorders            hypertension                           Common flushing, cerebrovascular              Uncommon accident§, transient ischaemic attack, hypertensive crisis‡,
vasculitis‡
Respiratory, thoracic and     bronchospasm‡                          Common mediastinal disorders cough, dyspnoea, epistaxis             Uncommon
Gastrointestinal disorders    abdominal pain                         Very common Constipation, flatulence, gastritis,   Common heartburn/acid reflux, diarrhea,
dyspepsia/epigastric discomfort,
nausea, vomiting, oesophagitis,
oral ulcer abdominal distention, bowel            Uncommon movement pattern change, dry mouth, gastroduodenal ulcer,
peptic ulcers including gastrointestinal perforation and bleeding, irritable bowel syndrome,
pancreatitis‡
Hepatobiliary disorders       ALT increased, AST increased           Common hepatitis‡                             Rare hepatic failure‡, jaundice‡            Rare†
Skin and subcutaneous         ecchymosis                             Common tissue disorders facial oedema, pruritus, rash,         Uncommon erythema‡, urticaria‡
Stevens-Johnson syndrome‡, toxic       Rare† epidermal necrolysis‡, fixed drug eruption‡
Musculoskeletal and           muscular cramp/spasm,                  Uncommon connective tissue disorders   musculoskeletal pain/stiffness
Renal and urinary disorders   proteinuria, serum creatinine          Uncommon increased, renal failure/renal insufficiency‡ (see section 4.4)
General disorders and                      asthenia/fatigue, flu-like disease              Common administration site conditions chest pain                                      Uncommon
Investigations                             blood urea nitrogen increased,                  Uncommon creatine phosphokinase increased,
hyperkalaemia, uric acid increased blood sodium decreased                          Rare
*Frequency Category: Defined for each Adverse Experience Term by the incidence reported in the clinical trials data base: Very Common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1000 to <1/100), Rare (≥1/10,000 to <1/1000), Very Rare (<1/10,000).
‡This adverse reaction was identified through post-marketing surveillance. Its reported frequency has been estimated based upon the highest frequency observed across clinical trial data pooled by indication and approved dose.
†The frequency category of “Rare” was defined per the Summary of Product Characteristics (SmPC) guidance (rev. 2, Sept 2009) on the basis of an estimated upper bound of the 95% confidence interval for 0 events given the number of subjects treated with ARCOXIA in the analysis of the Phase III data pooled by dose and indication (n=15,470).
ßHypersensitivity includes the terms "allergy", "drug allergy", "drug hypersensitivity", "hypersensitivity", "hypersensitivity NOS", "hypersensitivity reaction" and "nonspecific allergy".
§Based on analyses of long-term placebo and active controlled clinical trials, selective COX-2 inhibitors have been associated with an increased risk of serious thrombotic arterial events, including myocardial infarction and stroke. The absolute risk increase for such events is unlikely to exceed 1% per year based on existing data (uncommon).

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.

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: https://sideeffects.health.gov.il