ezetimibe/simvastatin

ezetimibe/simvastatin

Inegy (UK), Vytorin

Pharmacologic class: Combination selective cholesterol absorption inhibitor and HMG-CoA reductase inhibitor

Therapeutic class: Antihyperlipidemic

Pregnancy risk category X

Action

Inhibits cholesterol production in liver and blocks intestinal cholesterol absorption, which decreases intestinal delivery of cholesterol to liver and increases systemic cholesterol clearance. Net effect is reduction in levels of total cholesterol, low-density lipoproteins, apolipoprotein B, triglycerides, and non-high-density-lipoprotein cholesterol (non-HDL-C). Also increases HDL level.

Availability

Tablets: Vytorin 10/10 (10 mg ezetimibe/10 mg simvastatin), Vytorin 10/20 (10 mg ezetimibe/20 mg simvastatin), Vytorin 10/40 (10 mg ezetimibe/40 mg simvastatin), Vytorin 10/80 (10 mg ezetimibe/80 mg simvastatin)

⊘Indications and dosages

➣ High LDL levels in primary hypercholesterolemia or mixed hyperlipidemia

Adults: Dosage individualized, usually starting with Vytorin 10/20 P.O. daily. Patients requiring less aggressive LDL reduction may begin with Vytorin 10/10; patients needing LDL reductions of more than 55% may start with Vytorin 10/40.

➣ Elevated total cholesterol and LDL levels in homozygous familial hypercholesterolemia

Adults: Initially, Vytorin 10/40 or Vytorin 10/80 P.O. in evening

Dosage adjustment

• Severe renal insufficiency
• Moderate hepatic insufficiency

Contraindications

• Hypersensitivity to drug or its components
• Active hepatic disease or unexplained, persistent transaminase elevations
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• severe renal insufficiency
• history of hepatic disease
• substantial alcohol consumption
• concurrent cyclosporine therapy.

Administration

• Know that patient should be placed on standard cholesterol-lowering diet before receiving drug and should continue on this diet throughout therapy.
• Be aware that cholesterol and liver function tests should be done before therapy starts.
☞ Don't give to patient with severe renal insufficiency unless he has previously tolerated 5 mg or more of simvastatin.
• Give at least 2 hours before or 4 hours after bile acid sequestrant (if prescribed).
• Don't give with grapefruit juice.

Route	Onset	Peak	Duration
P.O.	Unknown	Unknown	Unknown

Adverse reactions

CNS: fatigue, headache

EENT: sinusitis, pharyngitis

GI: nausea, diarrhea, abdominal pain

Hepatic: hepatotoxicity (rare)

Musculoskeletal: arthralgia, myalgia, back pain, pain in extremities, myopathy, rhabdomyolysis (rare)

Respiratory: cough, upper respiratory tract infection

Other: influenza, hypersensitivity reactions

Interactions

Drug-drug . Amiodarone, verapamil: increased risk of myopathy and rhabdomyolysis

Cholestyramine: decreased ezetimibe blood level with further LDL reduction

Cyclosporine: increased ezetimibe blood level

CYP3A4 inhibitors (clarithromycin, cyclosporine, erythromycin, itraconazole, ketoconazole, nefazodone, protease inhibitors), gemfibrozil and other fibrates, niacin (in doses above 1 g/day): increased risk of myopathy

Digoxin: increased digoxin blood level

Warfarin: modest anticoagulant potentiation

Drug-diagnostic tests . Creatine kinase (CK), hepatic enzymes: increased levels

Drug-food . Grapefruit juice: increased risk of myopathy

Oat bran: impaired drug absorption

Drug-herbs . Chaparral, comfrey, eucalyptus, germander, jin bu huan, kava, skullcap, valerian: possible additive hepatotoxicity

St. John's wort: significant reduction in simvastatin bioavailability

Patient monitoring

• Monitor cholesterol levels and liver function test results before therapy starts and thereafter as indicated.
• Closely monitor patients with complicated medical histories, especially those with renal insufficiency from long-standing diabetes.
☞ Watch for unexplained muscle pain, tenderness, or weakness. Report this finding promptly and check CK level closely for evidence of myopathy.
☞ Discontinue drug if myopathy is diagnosed or suspected.
• Be aware that patients taking Vytorin 10/80 should have an additional liver function test before therapy starts, 3 months after titration, and periodically during first year.

Patient teaching

• Instruct patient to take 2 hours before or 4 hours after bile acid sequestrant (if prescribed).
• Advise patient not to take with large amounts of grapefruit juice.
• Teach patient about role of diet, exercise, and weight loss in lowering cholesterol.
☞ Tell patient that myopathy can occur when therapy starts or during dosage titration. Instruct him to immediately report unexplained muscle pain or tenderness or weakness.
• Advise patient to tell all prescribers he's taking this drug before starting any new drug.
• Caution female patient not to become pregnant or breastfeed while taking drug.
• Tell patient to limit or avoid alcohol use during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.