Ezentia Special Precautions

Use with Statins or Fenofibrate: Concurrent administration of ezetimibe with a specific statin or fenofibrate should be in accordance with the prescribing information for that medication.
Liver Enzymes: The reported incidence of consecutive elevations (≥3 X the upper limit of normal [ULN]) in hepatic transaminase levels was 0.5% for ezetimibe.
It was reported that when ezetimibe initiated concurrently with a statin, the incidence of consecutive elevations (≥3 X ULN) in hepatic transaminase levels was 1.3% for patients treated with ezetimibe administered with statins and 0.4% for patients treated with statins alone. These elevations in transaminases were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment. When ezetimibe is co-administered with a statin, liver tests should be performed at initiation of therapy and according to the recommendations of the statin. Should an increase in ALT or AST ≥3 X ULN persist, consider withdrawal of ezetimibe and/or the statin.
Myopathy/Rhabdomyolysis: There was no excess of myopathy or rhabdomyolysis associated with ezetimibe 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. The reported incidence of creatine phosphokinase (CPK) >10 X ULN was 0.2% for ezetimibe vs 0.1% for placebo, and 0.1% for ezetimibe co-administered with a statin vs 0.4% for statins alone. Risk for skeletal muscle toxicity increases with higher doses of statin, advanced age (>65), hypothyroidism, renal impairment, and depending on the statin used, concomitant use of other drugs.
Cases of myopathy and rhabdomyolysis have been reported with ezetimibe. Most patients who developed rhabdomyolysis were taking a statin prior to initiating ezetimibe. However, rhabdomyolysis has been reported with ezetimibe monotherapy and with the addition of ezetimibe to agents known to be associated with increased risk of rhabdomyolysis, such as fibrates. Ezetimibe and any statin or fibrate that the patient is taking concomitantly should be immediately discontinued if myopathy is diagnosed or suspected. The presence of muscle symptoms and a CPK level >10 X the ULN indicates myopathy.
Hepatic Impairment: Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate to severe hepatic impairment, ezetimibe is not recommended in these patients (see Pharmacology: Pharmacokinetics under Actions).
Ezetimibe given concomitantly with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations of hepatic transaminase levels (see Contraindications, Precautions and Pharmacology: Pharmacokinetics under Actions).
Fibrates: The safety and efficacy of ezetimibe administered with fibrates have not been established (see Interactions and Adverse Reactions).
Lactose: EZENTIA tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Renal Impairment: When used as monotherapy, no dosage adjustment of ezetimibe is necessary.
Use in Children: Efficacy and safety of ezetimibe co-administered with simvastatin in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia have been reported in adolescent boys (Tanner stage II or above) and in girls who were at least one year post-menarche.
In this limited information, there was generally no detectable effect on growth or sexual maturation in the adolescent boys or girls, or any effect on menstrual cycle length in girls. However, the effects of ezetimibe for a treatment period > 33 weeks on growth and sexual maturation have not been studied.
The safety and efficacy of ezetimibe co-administered with doses simvastatin above 40 mg daily have not been reported in paediatric patients 10 to 17 years of age.
Ezetimibe has not been studied in patients younger than 10 years of age or in pre-menarchal girls.
The long-term efficacy of therapy with ezetimibe in patients below 17 years of age to reduce morbidity and mortality in adulthood has not been studied.
Use in Elderly: No overall differences in safety and effectiveness were reported between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out (see Pharmacology: Pharmacokinetics under Actions).