Vytorin (Ezetimibe / Simvastatin) - Indications and Dosage

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.

Primary Hyperlipidemia

VYTORIN is indicated for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary (heterozygous familial and non-familial) hyperlipidemia or mixed hyperlipidemia.

Homozygous Familial Hypercholesterolemia (HoFH)

VYTORIN is indicated for the reduction of elevated total-C and LDL-C in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

Limitations of Use

No incremental benefit of VYTORIN on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established. VYTORIN has not been studied in Fredrickson type I, III, IV, and V dyslipidemias.

DOSAGE AND ADMINISTRATION

Recommended Dosing

The dosage range is 10/10 mg/day through 10/80 mg/day. The recommended usual starting dose is 10/20 mg/day. VYTORIN should be taken as a single daily dose in the evening, with or without food. Initiation of therapy with 10/10 mg/day may be considered for patients requiring less aggressive LDL-C reductions. Patients who require a larger reduction in LDL-C (greater than 55%) may be started at 10/40 mg/day. After initiation or titration of VYTORIN, lipid levels may be analyzed after 2 or more weeks and dosage adjusted, if needed.

Patients with Homozygous Familial Hypercholesterolemia

The recommended dosage for patients with homozygous familial hypercholesterolemia is VYTORIN 10/40 mg/day or 10/80 mg/day in the evening. VYTORIN should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Patients with Hepatic Impairment

No dosage adjustment is necessary in patients with mild hepatic impairment [see Warnings and Precautions].

Patients with Renal Impairment

No dosage adjustment is necessary in patients with mild or moderate renal impairment. However, for patients with severe renal insufficiency, VYTORIN should not be started unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. Caution should be exercised when VYTORIN is administered to these patients, and they should be closely monitored [see Warnings and Precautions; Clinical Pharmacology].

Geriatric Patients

No dosage adjustment is necessary in geriatric patients [see Clinical Pharmacology].

Coadministration with Other Drugs

[See Warnings and Precautions and Drug Interactions (7).]

Bile Acid Sequestrants

Dosing of VYTORIN should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant [see Drug Interactions].

Cyclosporine or Danazol

Caution should be exercised when initiating VYTORIN in the setting of cyclosporine. In patients taking cyclosporine or danazol, VYTORIN should not be started unless the patient has already tolerated treatment with simvastatin at a dose of 5 mg or higher. The dose of VYTORIN should not exceed 10/10 mg/day [see Drug Interactions].

Amiodarone or Verapamil

In patients taking amiodarone or verapamil concomitantly with VYTORIN, the dose should not exceed 10/20 mg/day [see Warnings and Precautions and Drug Interactions].

Other Concomitant Lipid-Lowering Therapy

The safety and effectiveness of VYTORIN administered with fibrates have not been established. Therefore, the combination of VYTORIN and fibrates should be avoided [see Warnings and Precautions and Drug Interactions (7.2 and 7.7) ].

There is an increased risk of myopathy when simvastatin is used concomitantly with fibrates (especially gemfibrozil). Combination therapy with gemfibrozil should be avoided because of an increase in simvastatin exposure with concomitant use. [See Warnings and Precautions and Drug Interactions (7.2 and 7.7) ].

DOSAGE FORMS AND STRENGTHS

• VYTORIN^® 10/10, (ezetimibe 10 mg/simvastatin 10 mg tablets) are white to off-white capsule-shaped tablets with code “311” on one side.
• VYTORIN^® 10/20, (ezetimibe 10 mg/simvastatin 20 mg tablets) are white to off-white capsule-shaped tablets with code “312” on one side.
• VYTORIN^® 10/40, (ezetimibe 10 mg/simvastatin 40 mg tablets) are white to off-white capsule-shaped tablets with code “313” on one side.
• VYTORIN^® 10/80, (ezetimibe 10 mg/simvastatin 80 mg tablets) are white to off-white capsule-shaped tablets with code “315” on one side.

HOW SUPPLIED/STORAGE AND HANDLING

No. 3873 — Tablets VYTORIN 10/10 are white to off-white capsule-shaped tablets with code “311” on one side.

They are supplied as follows:

NDC 66582-311-31 bottles of 30

NDC 66582-311-54 bottles of 90

NDC 66582-311-82 bottles of 1000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-311-87 bottles of 10,000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-311-28 unit dose packages of 100.

No. 3874 — Tablets VYTORIN 10/20 are white to off-white capsule-shaped tablets with code “312” on one side.

They are supplied as follows:

NDC 66582-312-31 bottles of 30

NDC 66582-312-54 bottles of 90

NDC 66582-312-82 bottles of 1000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-312-87 bottles of 10,000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-312-28 unit dose packages of 100.

No. 3875 — Tablets VYTORIN 10/40 are white to off-white capsule-shaped tablets with code “313” on one side.

They are supplied as follows:

NDC 66582-313-31 bottles of 30

NDC 66582-313-54 bottles of 90

NDC 66582-313-74 bottles of 500 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-313-86 bottles of 5000 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-313-52 unit dose packages of 50.

No. 3876 — Tablets VYTORIN 10/80 are white to off-white capsule-shaped tablets with code “315” on one side.

They are supplied as follows:

NDC 66582-315-31 bottles of 30

NDC 66582-315-54 bottles of 90

NDC 66582-315-74 bottles of 500 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-315-66 bottles of 2500 (If repackaged in blisters, then opaque or light-resistant blisters should be used.)

NDC 66582-315-52 unit dose packages of 50.

Storage

Store at 20-25°C (68-77°F). [See USP Controlled Room Temperature.] Keep container tightly closed.

Storage of 10,000, 5000, and 2500 count bottles

Store bottle of 10,000 VYTORIN 10/10 and 10/20, 5000 VYTORIN 10/40, and 2500 VYTORIN 10/80 capsule-shaped tablets at 20-25°C (68-77°F). [See USP Controlled Room Temperature.] Store in original container until time of use. When product container is subdivided, repackage into a tightly-closed, light-resistant container. Entire contents must be repackaged immediately upon opening.