urticaria
Ezetimibe (Zetia) Adverse Reactions
Ezetimibe, administered alone or with a HMG-CoA reductase inhibitor (’statin’), was generally well tolerated during pre-marketing clinical trials. The discontinuation rate due to adverse events during ezetimibe therapy was similar to placebo. For ezetimibe monotherapy, adverse events which were reported at a frequency >= 2% and exceeding placebo (regardless of causality) included: fatigue (2.2% vs. 1.8% placebo), abdominal pain (3% vs. 2.8% placebo), diarrhea (3.7% vs. 3% placebo), viral infection (2.2% vs. 1.8% placebo), pharyngitis (2.3% vs. 2.1% placebo), sinusitis (3.6% vs. 2.8% placebo), arthralgia (3.8% vs. 3.4% placebo), back pain (4.1% vs. 3.9% placebo), and cough (2.3% vs. 2.1% placebo). Four placebo-controlled trials evaluated the use of ezetimibe or statin monotherapy versus ezetimibe/statin combination therapy. Combination therapy included 10 mg PO once daily of ezetimibe coadministered with once daily dosing of either atorvastatin 10 - 80 mg/day, lovastatin 10 - 40 mg/day, pravastatin 10 - 40 mg/day, or simvastatin 10 - 80 mg/day. In general, adverse experiences were similar between ezetimibe given concurrently with a statin (ezetimibe/statin) vs. statin monotherapy. In patients receiving ezetimibe/statin vs. statin or ezetimibe monotherapy, adverse experiences reported in >= 2% of patients and at an incidence greater than placebo included: chest pain (unspecified) (1.8% ezetimibe/statin vs. 2% statin monotherapy vs. 3.4% ezetimibe monotherapy), dizziness (1.8% vs. 1.4% vs. 2.7%), fatigue (2.8% vs. 1.4% vs. 1.9%), headache (6.3% vs. 7.3% vs. 8%), abdominal pain (3.5% vs. 3.1% vs. 2.7%), diarrhea (2.8% vs. 2.9% vs. 3.4%), pharyngitis (2.3% vs. 2.5% vs. 3.1%), sinusitis (3.5% vs. 3.6% vs. 4.6%), upper respiratory infection (11.8% vs. 13.6% vs. 13.0%), arthralgia (3.4% vs. 4.3% vs. 3.8%), and back pain (4.3% vs. 3.7% vs. 3.4%).
During pre-marketing comparative clinical trials, the incidence of myalgia was 4.6% for placebo, 4.1% for HMG-CoA reductase inhibitor (’statin’) monotherapy, 4.5% for ezetimibe/statin combination therapy, and 5% for ezetimibe monotherapy. Combination therapy included 10 mg PO once daily of ezetimibe coadministered with once daily dosing of either atorvastatin 10 - 80 mg/day, lovastatin 10 - 40 mg/day, pravastatin 10 - 40 mg/day, or simvastatin 10 - 80 mg/day. During clinical trials, the incidence of elevated creatinine kinase concentrations (CPK > 10 times the upper limit of normal) was 0.1% for placebo, 0.1% for combination therapy (ezetimibe/statin), 0.4% for statin monotherapy, and 0.2% for ezetimibe monotherapy. There was no excess of myopathy or rhabdomyolysis associated with ezetimibe compared with the comparator groups (placebo or statin monotherapy). During postmarketing surveillance of ezetimibe use, myalgia, increased CPK serum concentrations, and very rarely, myopathy/rhabdomyolysis, have been reported. The myopathy risk is higher when ezetimibe is coadministered with statin therapy. Patients receiving ezetimibe should be monitored for signs and symptoms of myopathy and/or rhabdomyolysis/myoglobinuria (myalgia, muscle cramps, musculoskeletal pain, lethargy, fatigue, fever, and/or myasthenia).
In controlled clinical monotherapy studies, the incidence of consecutive elevations (>= 3 times the upper limit of normal) in serum transaminases (ALT/AST) was similar between ezetimibe monotherapy (0.5%) and placebo (0.3%). Although the adverse effect profile was similar in the HMG-CoA reductase inhibitor (’statin’) monotherapy group relative to the ezetimibe/statin group, the frequency of elevated hepatic enzymes was higher in patients receiving combination therapy with ezetimibe/statins than in patients treated with statin monotherapy. In controlled trials, the incidence of consecutive elevations in serum transaminases was 1.3% for ezetimibe/statin combination therapy vs. 0.4% for statin monotherapy. The elevations in transaminases were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation or continuation of therapy. During post-marketing surveillance, elevated hepatic enzymes and hepatitis have been reported. When ezetimibe is co-administered with a HMG-CoA reductase inhibitor, liver function tests (LFTs) should be evaluated prior to initiating therapy and repeated according to the recommendations of the specific HMG-CoA reductase inhibitor.
During post-marketing experience with ezetimibe therapy, hypersensitivity reactions, including angioedema, urticaria, arthralgia, and rash (unspecified), have been reported. In addition, nausea/vomiting, cholecystitis, cholelithiasis, pancreatitis, and thrombocytopenia have been reported.
[ Last revised: 2/3/2006 2:58:00 PM ]
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