VYTORIN ^® 10/10
(EZETIMIBE 10 MG/SIMVASTATIN 10 MG TABLETS)
VYTORIN ^® 10/20
(EZETIMIBE 10 MG/SIMVASTATIN 20 MG TABLETS)
VYTORIN ^® 10/40
(EZETIMIBE 10 MG/SIMVASTATIN 40 MG TABLETS)
VYTORIN ^® 10/80
(EZETIMIBE 10 MG/SIMVASTATIN 80 MG TABLETS)

VYTORIN contains ezetimibe, a selective inhibitor of intestinal cholesterol and related phytosterol absorption, and simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (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. The empirical formula is C₂₄H₂₁F₂NO₃ and its molecular weight is 409.4.

Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water. Its structural formula is:

Simvastatin, an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form, which is an inhibitor of HMG-CoA reductase. Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7- dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S- [1α,3α,7β,8β(2S*,4S*),-8aβ]]. The empirical formula of simvastatin is C₂₅H₃₈O₅ and its molecular weight is 418.57.

Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol. Its structural formula is:

VYTORIN is available for oral use as tablets containing 10 mg of ezetimibe, and 10 mg of simvastatin (VYTORIN 10/10), 20 mg of simvastatin (VYTORIN 10/20), 40 mg of simvastatin (VYTORIN 10/40), or 80 mg of simvastatin (VYTORIN 10/80). Each tablet contains the following inactive ingredients: butylated hydroxyanisole NF, citric acid monohydrate USP, croscarmellose sodium NF, hydroxypropyl methylcellulose USP, lactose monohydrate NF, magnesium stearate NF, microcrystalline cellulose NF, and propyl gallate NF.

Clinical studies have demonstrated that elevated levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo B), the major protein constituent of LDL, promote human atherosclerosis. In addition, decreased levels of high-density lipoprotein cholesterol (HDL-C) are associated with the development of atherosclerosis. Epidemiologic studies have established that cardiovascular morbidity and mortality vary directly with the level of total-C and LDL-C and inversely with the level of HDL-C. Like LDL, cholesterol-enriched triglyceride-rich lipoproteins, including very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and remnants, can also promote atherosclerosis. The independent effect of raising HDL-C or lowering triglycerides (TG) on the risk of coronary and cardiovascular morbidity and mortality has not been determined.

The hypocholesterolemic effect of ezetimibe was evaluated in cholesterol-fed Rhesus monkeys, dogs, rats, and mouse models of human cholesterol metabolism. Ezetimibe was found to have an ED₅₀ value of 0.5 µg/kg/day for inhibiting the rise in plasma cholesterol levels in monkeys. The ED₅₀ values in dogs, rats, and mice were 7, 30, and 700 µg/kg/day, respectively. These results are consistent with ezetimibe being a potent cholesterol absorption inhibitor.

In a rat model, where the glucuronide metabolite of ezetimibe (ezetimibe-glucuronide) was administered intraduodenally, the metabolite was as potent as ezetimibe in inhibiting the absorption of cholesterol, suggesting that the glucuronide metabolite had activity similar to the parent drug.

In 1-month studies in dogs given ezetimibe (0.03 to 300 mg/kg/day), the concentration of cholesterol in gallbladder bile increased ~2- to 4-fold. However, a dose of 300 mg/kg/day administered to dogs for one year did not result in gallstone formation or any other adverse hepatobiliary effects. In a 14-day study in mice given ezetimibe (0.3 to 5 mg/kg/day) and fed a low-fat or cholesterol-rich diet, the concentration of cholesterol in gallbladder bile was either unaffected or reduced to normal levels, respectively.

A series of acute preclinical studies was performed to determine the selectivity of ezetimibe for inhibiting cholesterol absorption. Ezetimibe inhibited the absorption of ¹⁴C-cholesterol with no effect on the absorption of triglycerides, fatty acids, bile acids, progesterone, ethyl estradiol, or the fat-soluble vitamins A and D.

In 4- to 12-week toxicity studies in mice, ezetimibe did not induce cytochrome P450 drug metabolizing enzymes. In toxicity studies, a pharmacokinetic interaction of ezetimibe with HMG-CoA reductase inhibitors (parents or their active hydroxy acid metabolites) was seen in rats, dogs, and rabbits.

A double-blind, randomized, 12-week study was performed in patients with a clinical and/or genotypic diagnosis of HoFH. Data were analyzed from a subgroup of patients (n=14) receiving simvastatin 40 mg at baseline. Increasing the dose of simvastatin from 40 to 80 mg (n=5) produced a reduction of LDL-C of 13% from baseline on simvastatin 40 mg. Coadministered ezetimibe and simvastatin equivalent to VYTORIN (10/40 and 10/80 pooled, n=9), produced a reduction of LDL-C of 23% from baseline on simvastatin 40 mg. In those patients coadministered ezetimibe and simvastatin equivalent to VYTORIN (10/80, n=5), a reduction of LDL-C of 29% from baseline on simvastatin 40 mg was produced.

VYTORIN is indicated as adjunctive therapy to diet for the reduction of elevated total-C, LDL-C, Apo B, TG, and non-HDL-C, and to increase HDL-C in patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia.

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.

Therapy with lipid-altering agents should be a component of multiple risk-factor intervention in individuals at increased risk for atherosclerotic vascular disease due to 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 diet and other non-pharmacological measures has been inadequate. (See NCEP Adult Treatment Panel (ATP) III Guidelines, summarized in Table 6.)

Prior to initiating therapy with VYTORIN, secondary causes for dyslipidemia (i.e., diabetes, hypothyroidism, obstructive liver disease, chronic renal failure, and drugs that increase LDL-C and decrease HDL-C [progestins, anabolic steroids, and corticosteroids]), should be excluded or, if appropriate, treated. A lipid profile should be performed to measure total-C, LDL-C, HDL-C and TG. For TG levels >400 mg/dL (>4.5 mmol/L), LDL-C concentrations should be determined by ultracentrifugation.

At the time of hospitalization for an acute coronary event, lipid measures should be taken on admission or within 24 hours. These values can guide the physician on initiation of LDL-lowering therapy before or at discharge.

Hypersensitivity to any component of this medication.

Active liver disease or unexplained persistent elevations in serum transaminases (see WARNINGS, Liver Enzymes).

Pregnancy and lactation. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Moreover, cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Because of the ability of inhibitors of HMG-CoA reductase such as simvastatin to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, VYTORIN is contraindicated during pregnancy and in nursing mothers. VYTORIN should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, VYTORIN should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus (see PRECAUTIONS, Pregnancy).

In clinical trials, there was no excess of myopathy or rhabdomyolysis 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 other lipid-lowering drugs. In clinical trials, the incidence of CK >10 X the upper limit of normal [ULN] was 0.2% for VYTORIN. (See PRECAUTIONS, Skeletal Muscle.)

Simvastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above 10 X ULN. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.

As with other HMG-CoA reductase inhibitors, the risk of myopathy/rhabdomyolysis is dose related. In a clinical trial database in which 41,050 patients were treated with simvastatin with 24,747 (approximately 60%) treated for at least 4 years, the incidence of myopathy was approximately 0.02%, 0.08% and 0.53% at 20, 40 and 80 mg/day, respectively. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.

All patients starting therapy with VYTORIN or whose dose of VYTORIN is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. VYTORIN therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when simvastatin treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with simvastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy.

Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients taking VYTORIN merit closer monitoring. Therapy with VYTORIN should be temporarily stopped a few days prior to elective major surgery and when any major medical or surgical condition supervenes.

In three placebo-controlled, 12-week trials, the incidence of consecutive elevations (≥3 X ULN) in serum transaminases was 1.7% overall for patients treated with VYTORIN and appeared to be dose-related with an incidence of 2.6% for patients treated with VYTORIN 10/80. In controlled long-term (48-week) extensions, which included both newly-treated and previously-treated patients, the incidence of consecutive elevations (≥3 X ULN) in serum transaminases was 1.8% overall and 3.6% for patients treated with VYTORIN 10/80. These elevations in transaminases were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.

It is recommended that liver function tests be performed before the initiation of treatment with VYTORIN, and thereafter when clinically indicated. Patients titrated to the 10/80-mg dose should receive an additional test prior to titration, 3 months after titration to the 10/80-mg dose, and periodically thereafter (e.g., semiannually) for the first year of treatment. Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) return to normal. Should an increase in AST or ALT of 3 X ULN or greater persist, withdrawal of therapy with VYTORIN is recommended.

VYTORIN should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained persistent transaminase elevations are contraindications to the use of VYTORIN.

Patients should be advised about substances they should not take concomitantly with VYTORIN and be advised to report promptly unexplained muscle pain, tenderness, or weakness (see ul below and WARNINGS, Myopathy/Rhabdomyolysis). Patients should also be advised to inform other physicians prescribing a new medication that they are taking VYTORIN.

In post-marketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported regardless of causality. Most patients who developed rhabdomyolysis were taking a statin prior to initiating ezetimibe. However, rhabdomyolysis has been reported very rarely with ezetimibe monotherapy and very rarely with the addition of ezetimibe to agents known to be associated with increased risk of rhabdomyolysis, such as fibrates.

Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, VYTORIN is not recommended in these patients. (See CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations.)

(See also CLINICAL PHARMACOLOGY, Drug Interactions)

Optic nerve degeneration was seen in clinically normal dogs treated with simvastatin for 14 weeks at 180 mg/kg/day, a dose that produced mean plasma drug levels about 12 times higher than the mean plasma drug level in humans taking 80 mg/day.

A chemically similar drug in this class also produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean plasma drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). This same drug also produced vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis in dogs treated for 14 weeks at 180 mg/kg/day, a dose that resulted in a mean plasma drug level similar to that seen with the 60 mg/kg/day dose.

CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels were seen in dogs treated with simvastatin at a dose of 360 mg/kg/day, a dose that produced mean plasma drug levels that were about 14 times higher than the mean plasma drug levels in humans taking 80 mg/day. Similar CNS vascular lesions have been observed with several other drugs of this class.

There were cataracts in female rats after two years of treatment with 50 and 100 mg/kg/day (22 and 25 times the human AUC at 80 mg/day, respectively) and in dogs after three months at 90 mg/kg/day (19 times) and at two years at 50 mg/kg/day (5 times).

The effects of VYTORIN on labor and delivery in pregnant women are unknown.

In rat studies, exposure to ezetimibe in nursing pups was up to half of that observed in maternal plasma. It is not known whether ezetimibe or simvastatin are excreted into human breast milk. Because a small amount of another drug in the same class as simvastatin is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women who are nursing should not take VYTORIN (see CONTRAINDICATIONS).

Of the patients who received VYTORIN in clinical studies, 792 were 65 and older (this included 176 who were 75 and older). The safety of VYTORIN was similar between these patients and younger patients. Greater sensitivity of some older individuals cannot be ruled out. (See CLINICAL PHARMACOLOGY, Special Populations and ADVERSE REACTIONS.)

VYTORIN has been evaluated for safety in more than 3800 patients in clinical trials. VYTORIN was generally well tolerated.

Table 8 summarizes the frequency of clinical adverse experiences reported in ≥2% of patients treated with VYTORIN (n=1236) and at an incidence greater than placebo regardless of causality assessment from three similarly designed, placebo-controlled trials.

The adverse reactions reported for VYTORIN are consistent with those previously reported with ezetimibe and/or simvastatin.

Other adverse experiences reported with ezetimibe in placebo-controlled studies, regardless of causality assessment: Body as a whole – general disorders: fatigue; Gastrointestinal system disorders: abdominal pain, diarrhea; Infection and infestations: infection viral, pharyngitis, sinusitis; Musculoskeletal system disorders: arthralgia, back pain; Respiratory system disorders: coughing.

The following adverse reactions have been reported in post-marketing experience, regardless of causality assessment:

Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria; arthralgia; myalgia; elevations in liver transaminases; hepatitis; thrombocytopenia; pancreatitis; nausea; dizziness; depression; cholelithiasis; cholecystitis; elevated creatine phosphokinase; and, very rarely, myopathy/rhabdomyolysis (see WARNINGS, Myopathy/Rhabdomyolysis).

Other adverse experiences reported with simvastatin in placebo-controlled clinical studies, regardless of causality assessment: Body as a whole – general disorders: asthenia; Eye disorders: cataract; Gastrointestinal system disorders: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, nausea; Skin and subcutaneous tissue disorders: eczema, pruritus, rash.

The following effects have been reported with other HMG-CoA reductase inhibitors. Not all the effects uled below have necessarily been associated with simvastatin therapy.

Musculoskeletal system disorders: muscle cramps, myalgia, myopathy, rhabdomyolysis, arthralgias.

Nervous system disorders: dysfunction of certain cranial nerves (including alteration of taste, impairment of extra-ocular movement, facial paresis), tremor, dizziness, memory loss, paresthesia, peripheral neuropathy, peripheral nerve palsy, psychic disturbances.

Ear and labyrinth disorders: vertigo.

Psychiatric disorders: anxiety, insomnia, depression, loss of libido.

Hypersensitivity Reactions: An apparent hypersensitivity syndrome has been reported rarely which has included one or more of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.

Gastrointestinal system disorders: pancreatitis, vomiting.

Hepatobiliary disorders: hepatitis, including chronic active hepatitis, cholestatic jaundice, fatty change in liver, and, rarely, cirrhosis, fulminant hepatic necrosis, hepatic failure, and hepatoma.

Metabolism and nutrition disorders: anorexia.

Skin and subcutaneous tissue disorders: alopecia, pruritus. A variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails) have been reported.

Reproductive system and breast disorders: gynecomastia, erectile dysfunction.

Eye disorders: progression of cataracts (lens opacities), ophthalmoplegia.

Laboratory Abnormalities: elevated transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, and bilirubin; thyroid function abnormalities.

Marked persistent increases of serum transaminases have been noted (see WARNINGS, Liver Enzymes). About 5% of patients taking simvastatin had elevations of CK levels of 3 or more times the normal value on one or more occasions. This was attributable to the noncardiac fraction of CK. Muscle pain or dysfunction usually was not reported (see WARNINGS, Myopathy/Rhabdomyolysis).

In controlled clinical studies in which simvastatin was administered concomitantly with cholestyramine, no adverse reactions peculiar to this concomitant treatment were observed. The adverse reactions that occurred were limited to those reported previously with simvastatin or cholestyramine.

In a 48-week controlled study in adolescent boys and girls who were at least 1 year post-menarche, 10-17 years of age with heterozygous familial hypercholesterolemia (n=175), the safety and tolerability profile of the group treated with simvastatin (10-40 mg daily) was generally similar to that of the group treated with placebo, with the most common adverse experiences observed in both groups being upper respiratory infection, headache, abdominal pain, and nausea (see CLINICAL PHARMACOLOGY, Special Populations and PRECAUTIONS, Pediatric Use).

No specific treatment of overdosage with VYTORIN can be recommended. In the event of an overdose, symptomatic and supportive measures should be employed.

In clinical studies, administration of ezetimibe, 50 mg/day to 15 healthy subjects for up to 14 days, or 40 mg/day to 18 patients with primary hypercholesterolemia for up to 56 days, was generally well tolerated.

A few cases of overdosage have been reported; most have not been associated with adverse experiences. Reported adverse experiences have not been serious.

A few cases of overdosage with simvastatin have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae.

The dialyzability of simvastatin and its metabolites in man is not known at present.

The patient should be placed on a standard cholesterol-lowering diet before receiving VYTORIN and should continue on this diet during treatment with VYTORIN. The dosage should be individualized according to the baseline LDL-C level, the recommended goal of therapy, and the patient’s response. (See NCEP Adult Treatment Panel (ATP) III Guidelines, summarized in Table 6.) VYTORIN should be taken as a single daily dose in the evening, with or without food.

The dosage range is 10/10 mg/day through 10/80 mg/day. The recommended usual starting dose is 10/20 mg/day. 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. See below for dosage recommendations for patients receiving certain concomitant therapies and for those with renal insufficiency.

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.

No dosage adjustment is necessary in patients with mild hepatic insufficiency (see PRECAUTIONS, Hepatic Insufficiency).

No dosage adjustment is necessary in patients with mild or moderate renal insufficiency. 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 CLINICAL PHARMACOLOGY, Pharmacokinetics and WARNINGS, Myopathy/Rhabdomyolysis).

No dosage adjustment is necessary in geriatric patients (see CLINICAL PHARMACOLOGY, Special Populations).

Dosing of VYTORIN should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant (see PRECAUTIONS, Drug Interactions).

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.

In patients taking amiodarone or verapamil concomitantly with VYTORIN, the dose should not exceed 10/20 mg/day (see WARNINGS, Myopathy/Rhabdomyolysis and PRECAUTIONS, Drug Interactions, Other drug interactions).

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, Myopathy/Rhabdomyolysis, and PRECAUTIONS, Drug Interactions, Other drug interactions).

There is an increased risk of myopathy when simvastatin is used concomitantly with fibrates (especially gemfibrozil). Therefore, although not recommended, if VYTORIN is used in combination with gemfibrozil, the dose should not exceed 10/10 mg daily (see WARNINGS, Myopathy/Rhabdomyolysis, and PRECAUTIONS, Drug Interactions, Other drug interactions).

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 bulers, then opaque or light-resistant bulers should be used.)

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

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

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

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

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

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

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 spans must be repackaged immediately upon opening.

Issued September 2007

Printed in USA

9619508

Manufactured for:
MERCK/Schering-Plough Pharmaceuticals
North Wales, PA 19454, USA

By:
MSD Technology Singapore Pte. Ltd.
Singapore 637766
Or
Merck Sharp & Dohme (Italia) S.p.A.
Via Emilia, 21
27100 – Pavia
Italy
Or
Merck Sharp & Dohme Ltd.
Cramlington
Northumberland, UK NE23 3JU

VYTORIN^® (ezetimibe/simvastatin) Tablets
Patient Information about VYTORIN (VI-tor-in)
Generic name: ezetimibe/simvastatin tablets

Read this information carefully before you start taking VYTORIN. Review this information each time you refill your prescription for VYTORIN as there may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about VYTORIN, ask your doctor. Only your doctor can determine if VYTORIN is right for you.