Ezetrol Side Effects

Clinical studies of up to 112 weeks duration in which EZETROL 10 mg daily was administered alone (n=2396), with a statin (n=11,308), or with fenofibrate (n=185) patients demonstrated: EZETROL was generally well tolerated, adverse reactions were usually mild and transient, the overall incidence of side effects reported with EZETROL was similar to that reported with placebo, and the discontinuation rate due to adverse experiences was comparable between EZETROL and placebo.
The following common (≥1/100, <1/10) or uncommon (≥1/1,000, <1/100); drug-related adverse experiences were reported in patients taking EZETROL alone (n=2396) and at a greater incidence than placebo (n=1159), or in patients taking EZETROL co-administered with a statin (n=11,308) and at a greater incidence than statin administered alone (n=9361).
EZETROL administered alone: Investigations: Uncommon: ALT and/or AST increased; blood CPK increased; gamma-glutamyltransferase increased; liver function test abnormal.
Respiratory, Thoracic and Mediastinal Disorders: Uncommon: cough.
Gastrointestinal Disorders: Common: abdominal pain; diarrhea; flatulence.
Uncommon: dyspepsia; gastroesophageal reflux disease; nausea.
Musculoskeletal and Connective Tissue Disorders: Uncommon: arthralgia; muscle spasms; neck pain.
Metabolism and Nutrition Disorders: Uncommon: decreased appetite.
Vascular Disorders: Uncommon: hot flush; hypertension.
General Disorders and Administration Site Condition: Common: fatigue.
Uncommon: chest pain; pain.
EZETROL co-administered with a statin: Investigations: Common: ALT and/or AST increased.
Nervous System Disorders: Common: headache.
Uncommon: paresthesia.
Gastrointestinal Disorders: Uncommon: dry mouth; gastritis.
Skin and Subcutaneous Tissue Disorders: Uncommon: pruritus; rash; urticaria.
Musculoskeletal and Connective Tissue Disorders: Common: myalgia.
Uncommon: back pain; muscular weakness; pain in extremity.
General Disorders and Administration Site Condition: Uncommon: asthenia; edema peripheral.
EZETROL co-administered with fenofibrate: Gastrointestinal Disorders: Common: abdominal pain.
In a multicenter, double-blind, placebo-controlled, clinical study in patients with mixed hyperlipidemia, 625 patients were treated for up to 12 weeks and 576 for up to 1 year. This study was not designed to compare treatment groups for infrequent events. Incidence rates (95% CI) for clinically important elevations (>3 X ULN, consecutive) in serum transaminases were 4.5% (1.9, 8.8) and 2.7% (1.2, 5.4) for fenofibrate monotherapy and EZETROL co-administered with fenofibrate, respectively, adjusted for treatment exposure. Corresponding incidence rates for cholecystectomy were 0.6% (0.0, 3.1) and 1.7% (0.6, 4.0) for fenofibrate monotherapy and EZETROL co-administered with fenofibrate, respectively (see PRECAUTIONS). There were no CPK elevations >10 X ULN in either treatment group in this study.
Patients with Coronary Heart Disease: In the IMPROVE-IT study, involving 18,144 patients treated with either ezetimibe/simvastatin 10/40 mg (n=9067; of whom 6% were uptitrated to ezetimibe/simvastatin 10/80 mg) or simvastatin 40 mg (n=9077; of whom 27% were uptitrated to simvastatin 80 mg), the safety profiles were similar during a median follow-up period of 6.0 years. Discontinuation rates due to adverse experiences were 10.6% for patients treated with ezetimibe/simvastatin and 10.1% for patients treated with simvastatin. The incidence of myopathy was 0.2% for ezetimibe/simvastatin and 0.1% for simvastatin, where myopathy was defined as unexplained muscle weakness or pain with a serum CK ≥10 times ULN or two consecutive observations of CK ≥5 and <10 times ULN. The incidence of rhabdomyolysis was 0.1% for ezetimibe/simvastatin and 0.2% for simvastatin, where rhabdomyolysis was defined as unexplained muscle weakness or pain with a serum CK ≥10 times ULN with evidence of renal injury, ≥5 X ULN and <10 X ULN on two consecutive occasions with evidence of renal injury or CK ≥10,000 IU/L without evidence of renal injury. The incidence of consecutive elevations of transaminases (≥3 X ULN) was 2.5% for ezetimibe/simvastatin and 2.3% for simvastatin. (See PRECAUTIONS.) Gallbladder-related adverse effects were reported in 3.1% vs 3.5% of patients allocated to ezetimibe/simvastatin and simvastatin, respectively. The incidence of cholecystectomy hospitalizations was 1.5% in both treatment groups. Cancer (defined as any new malignancy) was diagnosed during the trial in 9.4% vs 9.5%, respectively.
Laboratory Values: In controlled clinical monotherapy trials, the incidence of clinically important elevations in serum transaminases (ALT and/or AST ≥3 X ULN, consecutive) was similar between EZETROL (0.5%) and placebo (0.3%). In co-administration trials, the incidence was 1.3% for patients treated with EZETROL co-administered with a statin and 0.4% for patients treated with a statin alone. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment (see PRECAUTIONS).
Clinically important elevations of CPK (≥10 X ULN) in patients treated with EZETROL administered alone or co-administered with a statin were similar to elevations seen with placebo or statin administered alone, respectively.
Post-marketing Experience: The following adverse reactions have been reported in post-marketing experience, regardless of causality assessment: Blood and lymphatic system disorders: thrombocytopaenia.
Nervous system disorders: dizziness; paraesthesia.
Gastrointestinal disorders: nausea; pancreatitis; constipation.
Skin and subcutaneous tissue disorders: severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilic and systemic symptoms (DRESS) and erythema multiforme.
Musculoskeletal and connective tissue disorders: arthralgia; myalgia; myopathy/rhabdomyolysis (see PRECAUTIONS).
General disorders and administration site conditions: asthenia.
Immune system disorders: Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria.
Hepatobiliary disorders: hepatitis; cholelithiasis; cholecystitis; drug-induced liver injury.
Psychiatric disorders: depression.