Overview
11 DESCRIPTION Ezetimibe and simvastatin tablets contain ezetimibe, a selective inhibitor of intestinal cholesterol and related phytosterol absorption, and simvastatin, an HMG-CoA reductase inhibitor. The chemical name of ezetimibe is 1-(4-fluorophenyl)-3( R )-[3-(4-fluorophenyl)-3( S )-hydroxypropyl]-4( S )-(4-hydroxyphenyl)-2-azetidinone.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ezetimibe and Simvastatin Tablets Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. Ezetimibe and simvastatin tablets contain ezetimibe and simvastatin, two lipid-lowering compounds with complementary mechanisms of action. Ezetimibe and simvastatin tablets reduce elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and increases HDL-C through dual inhibition of cholesterol absorption and synthesis. Ezetimibe Ezetimibe reduces blood cholesterol by inhibiting the absorption of cholesterol by the small intestine. The molecular target of ezetimibe has been shown to be the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is involved in the intestinal uptake of cholesterol and phytosterols.
Indications
- 1 INDICATIONS AND USAGE Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. Ezetimibe and simvastatin tablets, which contain a cholesterol absorption inhibitor and an HMG-CoA reductase inhibitor (statin), are indicated as adjunctive therapy to diet to: •...
Common Doses
- 10 mg
- 40 mg
- 20 mg
- 80 mg
Dosage
2 DOSAGE AND ADMINISTRATION • Dose range is 10 mg/10 mg/day to 10 mg/40 mg/day. ( 2.1 ) • Recommended usual starting dose is 10 mg/10 mg or 10 mg/20 mg/day. ( 2.1 ) • Due to the increased risk of myopathy, including rhabdomyolysis, use of the 10 mg/80 mg dose of ezetimibe and simvastatin tablets should be restricted to patients who have been taking ezetimibe and simvastatin tablets 10 mg/80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. ( 2.
Contraindications
- 4 CONTRAINDICATIONS Ezetimibe and simvastatin tablets are contraindicated in the following conditions: • Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products) [ see Warnings and Precautions ( 5.1 ) ]. • Concomitant administration of gemfibrozil, cyclosporine, or danazol [ see Warnings and Precautions ( 5.1 ) ].
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: • Rhabdomyolysis and myopathy [ see Warnings and Precautions ( 5.1 ) ] • Liver enzyme abnormalities [ see Warnings and Precautions ( 5.3 ) ] • Common (incidence ≥ 2% and greater than placebo) adverse reactions in clinical trials: headache, increased ALT, myalgia, upper respiratory tract infection, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories, Inc. at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- 7 DRUG INTERACTIONS [ See Clinical Pharmacology ( 12.3 ). ] Ezetimibe and Simvastatin Tablets Drug Interactions Associated With Increased Risk of Myopathy/Rhabdomyolysis ( 2.3 , 2.4 , 4 , 5.1 , 7.1 , 7.2 , 7.3 , 7.8 , 12.3 ) Interacting Agents Prescribing Recommendations Strong CYP3A4 Inhibitors, (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, cobicistat-containing products), gemfibrozil, cyclosporine, danazol Contraindicated with ezetimibe and simvastatin tablets Niacin...