Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
ATOZET (or co-administration of ezetimibe and atorvastatin equivalent to ATOZET) has been evaluated for safety in more than 2400 patients in 7 clinical trials.
Tabulated list of adverse reactions

Adverse reactions observed in clinical studies of ATOZET (or co-administration of ezetimibe and atorvastatin equivalent to ATOZET) or ezetimibe or atorvastatin or reported from post-marketing use with ATOZET or ezetimibe or atorvastatin are listed in Table 3. These reactions are presented by system organ class and by frequency. Frequencies are defined as: very common (≥1/10); common ≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); and not known (cannot be estimated from the available data).

Table 3
Adverse Reactions
System organ class                             Adverse reaction
Frequency
Infections and infestations
Uncommon                                       influenza
Not known                                      nasopharyngitis
Blood and lymphatic system disorders
Not known                                      thrombocytopenia
Immune system disorders
Not known                                      hypersensitivity, including anaphylaxis, angioedema, rash, and urticaria
Metabolism and nutrition disorders
Not known                                      decreased appetite; anorexia; hyperglycaemia; hypoglycaemia
Psychiatric disorders
Uncommon                                    depression; insomnia; sleep disorder Not known                                   nightmares
Nervous system disorders
Uncommon                                    dizziness; dysgeusia; headache; paraesthesia Not known                                   hypoesthesia; amnesia; peripheral neuropathy Eye disorders
Not known                                   vision blurred; visual disturbance Ear and labyrinth disorders
Not known                                   tinnitus; hearing loss
Cardiac disorders
Uncommon                                    sinus bradycardia
Vascular disorders
Uncommon                                    hot flush
Not known                                   hypertension
Respiratory, thoracic and mediastinal disorders
Uncommon                                    dyspnoea
Not known                                   cough; pharyngolaryngeal pain; epistaxis Gastrointestinal disorders
Common                                      diarrhoea
Uncommon                                    abdominal discomfort; abdominal distension; abdominal pain; abdominal pain lower; abdominal pain upper; constipation; dyspepsia; flatulence; frequent bowel movements; gastritis; nausea; stomach discomfort
Not known                                   pancreatitis; gastro-oesophageal reflux disease; eructation; vomiting; dry mouth
Hepatobiliary disorders
Not known                                   hepatitis; cholelithiasis; cholecystitis; cholestasis; fatal and non-fatal hepatic failure
Skin and subcutaneous tissue disorders
Uncommon                                    acne; urticaria
Not known                                   alopecia; skin rash; pruritus; erythema multiforme; angioneurotic oedema; dermatitis bullous including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis
Musculoskeletal and connective tissue disorders
Common                                      myalgia
Uncommon                                    arthralgia; back pain; muscle fatigue; muscle spasms; muscular weakness; pain in extremity
Not known                                   myopathy/rhabdomyolysis; muscle rupture; tendinopathy, sometimes complicated by rupture; neck pain; joint swelling; myositis; lupus-like syndrome;
immune-mediated necrotizing myopathy (see section
4.4)
Reproductive system and breast disorders
Not known                                   gynaecomastia
General disorders and administration site conditions
Uncommon                                    asthenia; fatigue; malaise; oedema Not known                                   chest pain; pain; peripheral oedema; pyrexia Investigations
Uncommon                                    ALT and/or AST increased; alkaline phosphatase increased; blood creatine phosphokinase (CPK) increased; gamma-glutamyltransferase increased;
hepatic enzyme increased; liver function test abnormal;
weight increased
Not known                                   white blood cells urine positive 
Laboratory Values
In controlled clinical trials, the incidence of clinically important elevations in serum transaminases (ALT and/or AST ≥3 X ULN, consecutive) was 0.6% for patients treated with ATOZET. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline spontaneously or after discontinuation of therapy (see section 4.4).

The following adverse events have been reported with some statins:
•     sexual dysfunction
•     exceptional cases of interstitial lung disease, especially with long term therapy (see section 4.4)
•     diabetes mellitus: frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI> 30 kg/m2, raised triglycerides, history of hypertension) 
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
/https://sideeffects.health.gov.il