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:

• 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):

• 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.

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. 

Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 10/80-mg dose of VYTORIN should be restricted to patients who have been taking VYTORIN 10/80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.

Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 10/80-mg dose of VYTORIN, patients unable to achieve their LDL-C goal utilizing the 10/40-mg dose of VYTORIN should not be titrated to the 10/80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.

Co-administration of ezetimibe with simvastatin at doses greater than 40 mg/day has not been studied in adolescents. Also, VYTORIN has not been studied in patients younger than 10 years of age or in premenarchal girls. The pharmacokinetics of simvastatin has not been studied in the pediatric population.

Because the risk for myopathy is dose-related, Chinese patients should not receive VYTORIN 10/80 mg co-administered with lipid-modifying doses of niacin containing products.

Because renal impairment is a risk factor for statin-associated myopathy, doses of VYTORIN exceeding 10/20 mg should be used with caution and close monitoring in patients with moderate to severe renal impairment.

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use.

Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above ten times the upper limit of normal (ULN). The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared with other statin therapies with similar or greater LDL-C-lowering efficacy and compared with lower doses of simvastatin.

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins.

Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria have been reported. Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.

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.

VYTORIN is contraindicated with:

• 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) 
• Concomitant administration of gemfibrozil, cyclosporine, or danazol
• Women who are pregnant or may become pregnant
• Nursing mothers

Caution should be used when prescribing fenofibrates with VYTORIN, as these agents can cause myopathy when given alone and the risk is increased when they are co-administered.

Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin co-administered with colchicine, and caution should be exercised when prescribing VYTORIN with colchicine.

Cases of myopathy/rhabdomyolysis have been observed with simvastatin co-administered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products.

In patients taking Verapamil, Diltiazem, or Dronedarone, the dose of VYTORIN should not exceed 10/10 mg/day.

In patients taking Amiodarone, Amlodipine or Ranolazine, the dose of VYTORIN should not exceed 10/20 mg/day.

In patients taking Bile Acid Sequestrants, the dosing of VYTORIN should occur either greater than or equal to 2 hours before or greater than or equal to 4 hours after administration of a bile acid sequestrant.

Avoid grapefruit juice.

There have been postmarketing reports of increased INR in patients who had ezetimibe added to warfarin.

In one study, concomitant administration of digoxin with simvastatin resulted in a slight elevation in
plasma digoxin concentrations.

VYTORIN may cause fetal harm when administered to a pregnant woman. 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.

It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require VYTORIN treatment should not breastfeed their infants.

GoToSource

• Use in patients under 10 years of age. GoToSource

• Rheumatoid arthritis. GoToSource

⚠️ Patients with the SLCO1B1 allele gene are at greater risk for statin-induced myopathy.

Rhabdomyolysis (breakdown of muscle tissue). GoToSource

Myopathy (disorder of the skeletal muscles). GoToSource

Liver injury and toxic hepatitis. GoToSource

Immune-mediated necrotizing myopathy (muscle disease). GoToSource

Cognitive impairment (e.g., memory loss,forgetfulness, amnesia, memory impairment, confusion) and increased blood sugar. GoToSource

Interstitial lung disease. GoToSource

Acute kidney injury. GoToSource

Angioedema (swelling in deep layers of skin). GoToSource

Increased risk of cancer. GoToSource

Lawsuits filed for kidney damage, rhabdomyolysis and liver damage.