Ezetimibe (Zetia) Contraindications and Precautions
- breast-feeding
- children
- elderly
- hepatic disease
- myopathy
- pregnancy
Ezetimibe (Zetia) Contraindications and Precautions
NOTE: Concurrent administration of ezetimibe with a HMG-CoA reductase inhibitor (’statin’) should be in accordance with the product labeling for that specific HMG-CoA reductase inhibitor.
Due to the unknown clinical effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic disease, ezetimibe is not recommended in these patients. In patients with mild (Child-Pugh score 5 - 6), moderate (Child Pugh score 7 - 9), or severe hepatic impairment (Child-Pugh score 10 - 15), the mean AUC values for total ezetimibe are increased approximately 1.7-fold, 3 - 4-fold, or 4-fold, respectively, compared to healthy subjects. The combination of ezetimibe with a HMG-CoA reductase inhibitor is contraindicated in patients with active hepatic disease or unexplained persistent elevations in serum transaminases. The incidence of consecutive elevations (>= 3 times the upper limit of normal) in serum transaminases is similar between ezetimibe monotherapy (0.5%) and placebo (0.3%). However, combined therapy with ezetimibe plus a statin (ezetimibe/statin) results in a greater frequency of consecutive elevations in liver function tests (LFTs) compared to statin monotherapy (1.3% ezetimibe/statin vs. 0.4% statin monotherapy). These elevations in transaminases are generally asymptomatic, not associated with cholestasis, and generally return to baseline after discontinuation or continuation of therapy. When ezetimibe is co-administered with a HMG-CoA reductase inhibitor, liver LFTs should be evaluated prior to initiating therapy, and repeated according to the recommendations for the specific HMG-CoA reductase inhibitor.
Myopathy and rhabdomyolysis are known adverse reactions to HMG-CoA reductase inhibitors (’statins’) and other lipid-lowering drugs. According to the manufacturer, the frequency of myopathy (or complications such as rhabdomyolysis) associated with ezetimibe has not been excessive compared with the comparator control groups (placebo or statin monotherapy). During pre-marketing clinical trials, the incidence of CPK > 10 times the upper limit of normal has been reported to be 0.1% for placebo, 0.1% for ezetimibe/statin combination therapy, 0.4% for statin monotherapy, and 0.2% for ezetimibe monotherapy.
The effectiveness and safety of ezetimibe are similar between elderly patients and younger subjects. However, greater sensitivity of some elderly patients cannot be ruled out. During pre-marketing clinical trials, 948 elderly (aged > 65 years) patients have received ezetimibe (this included 206 participants aged >= 75 years). No dosage adjustments are needed in the elderly per the manufacturer. Also, no dosage adjustment of ezetimibe is needed in patients with renal impairment per the manufacturer.
Ezetimibe is classified by the FDA as a pregnancy risk category C drug. There are no adequate and well-controlled studies of ezetimibe in pregnant women. Ezetimibe should be used during pregnancy only if the potential benefit justifies the risk to the fetus. All HMG-CoA reductase inhibitors are contraindicated in pregnant and breast-feeding women. When ezetimibe is administered with a HMG-CoA reductase inhibitor in a female of childbearing potential or in a female who is lactating, refer to the pregnancy category and package labeling for the specific HMG-CoA reductase inhibitor. Ezetimibe is excreted into rat milk. It is not known whether ezetimibe is excreted into human milk; therefore, ezetimibe should not be used in nursing mothers unless the potential benefit justifies the potential risk to the infant.
The pharmacokinetics of ezetimibe in older children and adolescents (10 - 18 years) are similar to that observed for adults. Treatment experience with ezetimibe in children and adolescents is limited to 4 patients (9 - 17 years) with sitosterolemia and 5 patients (11 - 17 years) with homozygous familial hypercholesterolemia. Ezetimibe is not recommended for use in children < 10 years of age.
[ Last revised: 11/25/2002 11:01:00 AM ]
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