Ezetimibe (Zetia drug)
Manufacturer: Schering Corporation, Kenilworth NJ, for Merck/Schering-Plough Pharmaceuticals, North Wales, PA (joint venture)
Indications: Primary hypercholesterolemia. Eze-timibe can be prescribed in several situations:
- As monotherapy. Ezetimibe generic, administered alone, is indicated as adjunctive therapy to an appropriate diet to reduce elevated total cholesterol (total-C), low-density lipopro-tein-cholesterol (LDL-C, or the “bad” cholesterol), and apo- lipoprotein B (apoB) in patients with primary (heterozygous familial and nonfamilial) hypercholesterolemia.
- In combination with HMG-CoA reductase inhibitors. Ezetimibe, administered in combination with a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is indicated as adjunctive therapy to dietary measures to reduce elevated total-C, LDL-C, and apoB in patients with primary (heterozygous familial and nonfamil-ial) hypercholesterolemia.
- As therapy for homozygous familial hypercholesterolemia (HoFH). The combination of ezetimibe and atorvastatin or simvastatin is indicated to decrease elevated total-C and LDL-C levels in patients with hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL aphere-sis) or when such treatments are unavailable.
- As therapy for homozygous sitosterolemia. Ezetimibe is indicated as adjunctive therapy to dietary restriction to decrease elevated concentrations of the plant sterols sitosterol and campesterol in patients with homozygous familial sitos-terolemia.
Therapy with lipid-altering agents should be a component of intervention in individuals with multiple risk factors who are at increased risk for atherosclerotic vascular disease caused by hypercholesterolemia. Lipid-altering agents should be used in addition to an appropriate diet (including restriction of saturated fat and cholesterol) and when the response to dietary and other nonpharmacological measures has been inadequate.
Drug Class: Ezetimibe is an antihyperlipidemic agent. official canadian pharmacy
Uniqueness of Drug: Ezetimibe is classified as a lipid-lowering compound that selectively inhibits the intestinal absorption of cholesterol and related phytosterols (plant sterols). Ezetimibe causes reductions in total-C, LDL-C, apoB, and triglycerides and also causes increases in high-density lipoprotein-cholesterol (HDL-C, or the “good” cholesterol) in patients with hypercholesterolemia. Administration of ezetimibe with an HMG-CoA reductase inhibitor is effective in improving serum total-C, LDL-C, apoB, triglycerides, and HDL-C beyond either treatment alone.
Precautions: Concurrent administration of ezetimibe with a specific HMG-CoA reductase inhibitor should be used in accordance with the product labeling for the HMG-CoA reductase inhibitor.
Liver Enzymes: In controlled clinical monotherapy studies, the incidence of consecutive elevations (>3 x the upper limit of normal) in serum transaminase levels was similar between ezetimibe (0.5%) and placebo (0.3%).
In controlled clinical combination studies of ezetimibe that have been initiated concurrently with an HMG-CoA reductase inhibitor, the incidence of consecutive elevations (>3 x the upper limit of normal) in serum transaminase concentrations was 1.3% for patients receiving ezetimibe along with HMG-CoA reductase inhibitors and 0.4% for patients receiving HMG-CoA reductase inhibitors alone. These elevated transaminase levels were generally asymptomatic, were not associated with cholestasis, and returned to baseline measurements with discontinuation of therapy or with continued treatment. When eze-timibe is co-administered with an HMG-CoA reductase inhibitor, liver function tests should be performed at initiation of therapy and according to the recommendations for the HMG-CoA reductase inhibitor.
Skeletal Muscle: In clinical trials, no excess of myopathy or rhabdomyolysis was associated with ezetimibe, compared with the relevant control arm (placebo or HMG-CoA reductase inhibitor alone). However, myopathy and rhabdomyolysis are known adverse reactions to HMG-CoA reductase inhibitors and to other lipid-lowering drugs. In clinical trials, the incidence of creatine phosphokinase (CPK) above 10 times the upper limit of normal was 0.2% for ezetimibe versus 0.1% for placebo and 0.1% for ezetimibe co-administered with an HMG-CoA reductase inhibitor versus 0.4°% for HMG-CoA reductase inhibitors alone.
Hepatic Insufficiency: Ezetimibe is not recommended in patients with moderate or severe hepatic insufficiency because of the unknown effects of the increased exposure to this drug.
Dosage: A standard cholesterol-lowering diet should be prescribed before the patient receives ezetimibe, and the patient should continue on this diet during medical therapy. The recommended dose is 10 mg once daily. Ezetimibe can be administered with or without food.
Ezetimibe may be administered with an HMG-CoA reduc-tase inhibitor for an incremental effect. For convenience, the daily dose of ezetimibe may be taken at the same time as the HMG-CoA reductase inhibitor, according to the dosing recommendations for the latter.
No dosage adjustment is necessary in patients with mild hepatic insufficiency, in patients with renal insufficiency, or in geriatric patients. Dosing of ezetimibe should take place either at or more than two hours before, or at or more than four hours after, the administration of a bile acid sequestrant.
P&T Committee Considerations: Ezetimibe is the first in a new class of cholesterol-lowering agents that inhibit the intestinal absorption of cholesterol. The Food and Drug Administration (FDA) has approved the once-daily tablet of 10 mg for use either alone or together with statins in patients with high cholesterol levels to reduce LDL-C and total-C. Of the estimated 13 million patients taking statins, 60% continue to have higher-than-recommended LDL-C concentrations; thus, it is thought that ezetimibe, in combination with statins, might provide a new option to help patients achieve therapeutic goals. This is particularly important in view of last year’s changes in the National Institutes of Health’s cholesterol guidelines, which substantially increased the number of Americans eligible for drug therapy and proposed lower cholesterol goals for many patients. Co-administered with atorvastatin or simvastatin, eze-timibe further lowered LDL-C, decreased triglyceride levels, and increased HDL cholesterol levels.
Ezetimibe canadian should be included in the formulary as an option in the treatment of hypercholesterolemia as therapy alone or in combination with an HMG-CoA reductase inhibitor when diet and exercise have been inadequate for cholesterol control.
The average wholesale price (AWP) of ezetimibe is $57.90 for a bottle of 30 tablets (a month’s supply).