Ezetrol Special Precautions

When Ezetrol is to be administered with a statin or with fenofibrate, which is contraindicated during pregnancy and lactation, refer to the information for that particular statin or fibrate.
Liver Enzymes: In controlled co-administration trials in patients receiving Ezetrol with a statin, consecutive transaminase elevations [≥3 times the upper limit of normal (ULN)] have been observed. When Ezetrol is co-administered with a statin, liver function tests should be performed at initiation of therapy and according to the recommendations of the statin. (See Side Effects.)
Skeletal Muscle: In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with Ezetrol compared with the relevant control arm (placebo or statin alone). However, myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs. In clinical trials, the incidence of creatinine phosphokinase level (CPK) >10 times ULN was 0.2% for Ezetrol versus 0.1% for placebo and 0.1% for Ezetrol co-administered with a statin vs 0.4% for statins alone.
In post-marketing experience with Ezetrol, cases of myopathy and rhabdomyolysis have been reported regardless of causality. Most patients who developed rhabdomyolysis were taking a statin prior to initiating Ezetrol. However, rhabdomyolysis has been reported very rarely with Ezetrol monotherapy and very rarely with the addition of Ezetrol to agents known to be associated with increased risk of rhabdomyolysis. All patients starting therapy with Ezetrol should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. Ezetrol and any statin that the patient is taking concomitantly should be immediately discontinued if myopathy is diagnosed or suspected. The presence of these symptoms and a CPK level >10 times the ULN indicates myopathy.
Hepatic Insufficiency: Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, Ezetrol is not recommended in these patients [see Pharmacokinetics: Characteristics in Patients (Special Populations) under Actions].
Fibrates: The co-administration of ezetimibe with fibrates other than fenofibrate has not been studied. Therefore, co-administration of Ezetrol and fibrates (other fenofibrate) is not recommended (see Interactions).
Fenofibrates: If cholelithiasis is suspected in a patient receiving Ezetrol and fenofibrate, gallbladder studies are indicated and alternative lipid-lowering therapy should be considered (see Side Effects and product information for fenofibrate).
Cyclosporine: Caution should be exercised when initiating ezetimibe in the setting of cyclosporine. Cyclosporine concentrations should be monitored in patients receiving Ezetrol and cyclosporine (see Interactions).
Anticoagulants: If Ezetrol is added to warfarin, another coumarin anticoagulant or fluindione, the International Normalized Ratio (INR) should be appropriately monitored (see Interactions).
Effects on the Ability to Drive or Operate Machinery: No studies of the effects on the ability to drive and use of machines have been performed. However, ezetimibe is not expected to affect the ability to drive and use machines.
Use in pregnancy: No clinical data on exposed pregnancies are available. Animal studies of ezetimibe administered alone do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development. However, caution should be exercised when prescribing to pregnant women.
When ezetimibe was given with lovastatin, simvastatin, pravastatin or atorvastatin, no teratogenic effects were observed in embryo-fetal development studies in pregnant rats. In pregnant rabbits, a low incidence of skeletal malformations was observed.
When ezetimibe is to be administered with a statin, which is contraindicated during pregnancy and lactation, please refer to the information for that particular statin.
Use in lactation: Studies in rats have shown that ezetimibe is excreted in milk. It is not known whether ezetimibe is excreted into human breast milk. Therefore, Ezetrol should not be used in nursing mothers unless the potential benefit justifies the potential risk to the infant.