Ezetimibe / Simvastatin

Trade Names:
Vytorin 10/10
- Tablets ezetimibe 10 mg/simvastatin 10 mg

Trade Names:
Vytorin 10/20
- Tablets ezetimibe 10 mg/simvastatin 20 mg

Trade Names:
Vytorin 10/40
- Tablets ezetimibe 10 mg/simvastatin 40 mg

Trade Names:
Vytorin 10/80
- Tablets ezetimibe 10 mg/simvastatin 80 mg

Pharmacology

Inhibits absorption of cholesterol by the small intestine.

Inhibits the conversion of HMG-CoA to mevalonate, an early step in the biosynthetic pathway for cholesterol.

Indications and Usage

Adjunctive treatment to diet for reduction of elevated total-cholesterol, LDL cholesterol, triglycerides, non-HDL cholesterol, and apolipoprotein B (Apo B), and to increase HDL cholesterol in patients with primary hypercholesterolemia or mixed hyperlipidemia; as an adjunct to other lipid-lowering treatment for the reduction of total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia.

Contraindications

Active liver disease or unexplained persistent elevations in serum transaminases; pregnancy and lactation; hypersensitivity to any component of the product.

Dosage and Administration

PO Dosage range is 10/10 mg through 10/80 mg daily in the evening. Start with 10/20 mg daily. Lipid levels may be analyzed after 2 or more wk and dosage adjusted. For patients requiring a large reduction in LDL cholesterol (more than 55%), therapy may be started at 10/40 mg daily.

PO 10/40 mg daily or 10/80 mg daily in the evening. Use as an adjunct to other lipid lowering treatments.

General Advice

Administer without regard to meals. Administer with food if GI upset occurs.

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F).

Drug Interactions

Risk of myopathy/rhabdomyolysis may be increased. Dose of ezetimibe/simvastatin should not exceed 10/20 mg daily.

Aluminum and magnesium antacids decreased C _max of ezetimibe by 30%.

Ezetimibe concentrations may be reduced, decreasing the therapeutic effect. Give at least 2 h before or 4 h after the bile acid sequestrant.

Simvastatin concentrations may be reduced, decreasing the efficacy.

Exposure to ezetimibe may be increased, especially in patients with severe renal function impairment. Dose of ezetimibe/simvastatin should not exceed 10/10 mg daily.

Digoxin plasma concentrations may be slightly elevated.

Ezetimibe and simvastatin concentrations may be increased. Avoid coadministration.

Risk of myopathy may be increased, especially with doses of niacin 1 g/day or more.

May reduce the elimination of simvastatin, increasing the risk of myopathy. Avoid coadministration.

Simvastatin peak plasma concentrations may be reduced.

Coadministration may result in decreased simvastatin levels.

The anticoagulant effect, as measured by the INR, may be modestly potentiated.

Laboratory Test Interactions

None well documented.

Adverse Reactions

The incidences stated for the following adverse reactions were reported with Vytorin (ezetimibe/simvastatin) administration. Adverse reactions occurring with administration of either ezetimibe or simvastatin can be found in their respective monographs.

CNS

Headache (7%).

Hepatic

Cholelithiasis, cholecystitis, elevated CPK, elevated liver transaminases, (postmarketing).

Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria (postmarketing).

Musculoskeletal

Myalgia (4%); pain in extremity (2%); arthralgia (postmarketing).

Pulmonary

Upper respiratory tract infection (4%).

Miscellaneous

Influenza (3%); myopathy, nausea, pancreatitis, rhabdomyolysis, thrombocytopenia (postmarketing).

Precautions

Pregnancy

Category X .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Use with caution in patients with severe renal function impairment.

Hepatic Function

Use is not recommended in patients with moderate or severe hepatic function impairment.

Hepatotoxicity

Ensure that serum transaminases are determined before starting therapy and periodically thereafter as clinically indicated. For patients being titrated to 10/80 mg dose, ensure that transaminases are determined before titration, 3 mo after titration to 10/80 mg dose, and periodically thereafter (eg, every 6 mo) for first yr of treatment. If elevated serum transaminase levels develop during treatment, repeat levels more frequently. If transaminase levels rise to 3 times upper limit of normal or greater and persist, be prepared to discontinue therapy.

Liver dysfunction

Use with caution in patients who consume substantial quantities of alcohol or who have history of liver disease. Marked, persistent increases in serum transaminases can occur.

Myopathy/rhabdomyolysis

Simvastatin administration has been associated with dose-related myopathy/rhabdomyolysis. Discontinue therapy immediately if myopathy occurs or is suspected.

Secondary causes of hyperlipidemia

Rule out or treat secondary causes of hyperlipidemia before starting treatment.

Skeletal muscle effects

Rhabdomyolysis with renal function impairment secondary to myoglobinuria has occurred with statin administration. Consider myopathy in any patient with diffuse myalgias, muscle tenderness or weakness, or marked CPK elevation.

Overdosage

Symptoms

Limited data are available. Supportive treatment is recommended.

Patient Information

• Explain name, dose, action, potential side effects of medication, and LDL-C goal.
• Advise patient that dose of medication may change based on results of cholesterol blood tests in an effort to reach LDL-C goal.
• Review other substances (eg, grapefruit juice) and medications (eg, fibrates, potent CYP3A4 inhibitors) that should not be taken with this medication.
• Advise patient to take prescribed dose once daily in the evening without regard to meals, but to take with food if stomach upset occurs.
• Advise patient that if a dose is missed to take as soon as remembered but to never take more than 1 dose of medicine a day.
• Advise patient that drug helps control, but does not cure, cholesterol abnormality and to continue taking drug as prescribed when LDL-C goal has been met.
• Instruct patient to continue taking other cholesterol-lowering medications as prescribed by health care provider.
• Advise patient who is also taking a bile acid sequestrant (eg, cholestyramine) to take the ezetimibe/simvastatin at least 2 h before or 4 h after the sequestrant.
• Instruct patient to immediately notify health care provider if experiencing any unexplained muscle pain, tenderness, and/or weakness, or if they note any other unusual feelings.
• Emphasize to patient importance of other modalities on cholesterol control: dietary changes (reduce saturated fat intake, increase soluble fiber intake), weight control, regular exercise, smoking cessation.
• Advise women of childbearing potential to use effective contraception during treatment with ezetimibe/simvastatin.

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Ezetimibe/Simvastatin Side Effects

Compare Ezetimibe/Simvastatin with other medications for the treatment of:

High Cholesterol, High Cholesterol, Familial Heterozygous, High Cholesterol, Familial Homozygous

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