Indicated for:

Reductions in Risk of CHD Mortality and Cardiovascular Events:

In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, FLOLIPID is indicated to:

• Reduce the risk of total mortality by reducing CHD deaths
• Reduce the risk of non-fatal myocardial infarction and stroke
• Reduce the need for coronary and non-coronary revascularization procedures

Hyperlipidemia:

• Reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIb)
• Reduce elevated TG in patients with hypertriglyceridemia (Fredrickson type IV hyperlipidemia)
• Reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia (Fredrickson type III hyperlipidemia)
• Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia (HoFH) as an adjunct to other lipid lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable

Adolescent Patients with Heterozygous Familial Hypercholesterolemia (HeFH):

FLOLIPID is indicated as an adjunct to diet to reduce total-C, LDL-C, and Apo B levels in adolescent boys and girls who are at least one year post-menarche, 10 to 17 years of age, with HeFH, if after an adequate trial of diet therapy the following findings are present:

1. LDL cholesterol remains ≥190 mg/dL; or

2. LDL cholesterol remains ≥160 mg/dL and

• there is a positive family history of premature cardiovascular disease (CVD) or
• two or more other CVD risk factors are present in the adolescent patient

The minimum goal of treatment in pediatric and adolescent patients is to achieve a mean LDL-C <130 mg/dL. The optimal age at which to initiate lipid-lowering therapy to decrease the risk of symptomatic adulthood CAD has not been determined.

FLOLIPID has not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).

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

Patients who are currently tolerating the an 80-mg dose of FLOLIPID who need to be initiated on interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.

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

Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg co-administered with lipid-modifying doses (greater than or equal to 1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day co administered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg co-administered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with co-administration of simvastatin with lipid-modifying doses of niacin containing products observed in Chinese patients applies to other Asian patients.

FLOLIPID is contraindicated in the following conditions:

• 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
• Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels
• Women who are pregnant or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. 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. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. FLOLIPID 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, FLOLIPID should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus
• Nursing mothers. 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 treatment with FLOLIPID should not breastfeed their infants

Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (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 statin activity in plasma. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment.

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

The drug 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 transaminase elevations are contraindications to the use of simvastatin.

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

Marked persistent increases of hepatic transaminases have been noted. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported.

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

The risk of myopathy and rhabdomyolysis is increased by high levels of statin activity in plasma. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs which inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, and the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, cobicistat-containing products, or grapefruit juice. Combination of these drugs with simvastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with simvastatin must be suspended during the course of treatment.

Caution should be used when prescribing other fibrates with simvastatin, 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 simvastatin with colchicine.

The benefits of the combined use of simvastatin with the following drugs should be carefully weighed against the potential risks of combinations: other lipid-lowering drugs (other fibrates, ≥1 g/day of niacin, or, for patients with HoFH, lomitapide), amiodarone, dronedarone, verapamil, diltiazem, amlodipine, or ranolazine.

Do not exceed 20 mg simvastatin daily when administration with Verapamil, Diltiazem, Dronedarone.

For patients with HoFH, do not exceed 20 mg simvastatin daily with Lomitapide.

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

Women of childbearing potential, who require treatment with FLOLIPID for a lipid disorder, should be advised to use effective contraception. For women trying to conceive, discontinuation of FLOLIPID should be considered. If pregnancy occurs, FLOLIPID should be immediately discontinued.

FLOLIPID is contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development.

Because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking simvastatin should not nurse their infants.

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• Use in patients under 10 years of age. GoToSource

• Prophylaxis of adverse cardiovascular outcomes post-acute-coronary-syndrome hospitalization and prophylaxis of atrial fibrillation among patients with stable coronary artery disease. GoToSource

• Relapsing-remitting multiple sclerosis. GoToSource 

• Stage I-II breast cancer. GoToSource

• Alzheimer disease. GoToSource

• Reduce neuroinflammation in parkinson’s disease. GoToSource

• Colorectal cancer. GoToSource

• Rheumatoid arthritis, systemic lupus erythematosus and chronic obstructive pulmonary disease. GoToSource

• Acute myeloid leukemia. GoToSource

• Lung cancer. GoToSource

• Nephrotic syndrome. GoToSource

• Radiotherapy-induced lung toxicity. GoToSource

• Intracerebral hemorrhage. GoToSource

⚠️  Patients with SLCO1B1 increases systemic exposure to simvastatin with increased risk of muscle toxicity.

Myalgia (muscle pain), abdominal pain, constipation, upper respiratory infections, atrial fibrillation (irregular heartbeat), cholestatic hepatitis, jaundice, liver failure, bilateral leg compartment syndrome (increased pressure within a muscle compartment) and rhabdomyolysis (destruction or damage of skeletal muscle). GoToSource

Inflammatory bowel disease (chronic inflammation of digestive tract). GoToSource

Type 2 diabetes. GoToSource

Kidney injury. GoToSource

Myopathy (disease of skeletal muscle). GoToSource

Immune-mediated necrotizing myopathy (muscle disease). GoToSource

Cognitive deficits including memory loss. GoToSource

Exacerbation of myasthenia gravis, MELAS syndrome and lactic acidosis (too much acid in the body). GoToSource

Lawsuits filed for rhabdomyolysis, immune-mediated necrotizing myopathy, liver injury and development of diabetes.