Ezetrol Side Effects

Clinical studies of up to 112 weeks duration in which Ezetimibe (EZETROL) Tablet 10 mg daily was administered alone (n=2396), with a statin (n=11,308), or with fenofibrate (n=185), patients demonstrated: Ezetimibe (EZETROL) Tablet was generally well tolerated, adverse reactions were usually mild and transient, the overall incidence of side effects reported with Ezetimibe (EZETROL) Tablet was similar to that reported with placebo, and the discontinuation rate due to adverse experiences was comparable between Ezetimibe (EZETROL) Tablet 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 Ezetimibe (EZETROL) Tablet alone (n=2396) and at a greater incidence than placebo (n=1159), or in patients taking Ezetimibe (EZETROL) Tablet co-administered with a statin (n=11,308) and at a greater incidence than statin administered alone (n=9361).
Ezetimibe (EZETROL) Tablet 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.
Ezetimibe (EZETROL) Tablet 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.
Ezetimibe (EZETROL) Tablet 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 Ezetimibe (EZETROL) Tablet 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 Ezetimibe (EZETROL) Tablet 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 toezetimibe/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.
Patients with Chronic Kidney Disease: In the Study of Heart and Renal Protection (SHARP), involving over 9000 patients treated with a fixed dose combination of Ezetimibe (EZETROL) Tablet 10 mg with simvastatin 20 mg daily (n=4650) or placebo (n=4620), the safety profiles were comparable during a median follow-up period of 4.9 years. In this trial, only serious adverse events and discontinuations due to any adverse events were recorded. Discontinuation rates due to adverse events were comparable (10.4% in patients treated with Ezetimibe (EZETROL) Tablet combined with simvastatin, 9.8% in patients treated with placebo). The incidence of myopathy/rhabdomyolysis was 0.2% in patients treated with Ezetimibe (EZETROL) Tablet combined with simvastatin and 0.1% in patients treated with placebo. Consecutive elevations of transaminases (>3 X ULN) occurred in 0.7% of patients treated with Ezetimibe (EZETROL) Tablet combined with simvastatin compared with 0.6% of patients treated with placebo. (See PRECAUTIONS). In this trial, there were no statistically significant increases in the incidence of pre-specified adverse events, including cancer (9.4% for Ezetimibe (EZETROL) Tablet combined with simvastatin, 9.5% for placebo), hepatitis, cholecystectomy or complications of gallstones or pancreatitis.
Pediatric (6 to 17 Years of Age) Patients: In a study involving pediatric (6 to10 years of age) patients with heterozygous familial or non-familial hypercholesterolemia (n=138), the safety and tolerability profile of the group treated with Ezetimibe (EZETROL) Tablet was similar to that of adult patients treated with Ezetimibe (EZETROL) Tablet (see Pediatric Use under PRECAUTIONS).
In a study involving adolescent (10 to 17 years of age) patients with heterozygous familial hypercholesterolemia (n=248), the safety and tolerability profile of the group co-administered Ezetimibe (EZETROL) Tablet and simvastatin was similar to that of adult patients co-administered Ezetimibe (EZETROL) Tablet and simvastatin (see USE IN CHILDREN under PRECAUTIONS).
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 Ezetimibe (EZETROL) Tablet (0.5 %) and placebo (0.3%). In co-administration trials, the incidence was 1.3% for patients treated with Ezetimibe (EZETROL) Tablet 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 Ezetimibe (EZETROL) Tablet 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: Pancreatitis; constipation.
Skin and Subcutaneous Tissue Disorders: Erythema multiforme.
Musculoskeletal and Connective Tissue Disorders: 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.
Psychiatric Disorders: Depression.