Vytostad 10/10

Rx

Indications

• Primary hyperlipidemia
  Vytostad 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)
  Vytostad 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.

Dosage

Recommended dosing

• The usual dosage range is ezetimibe/simvastatin 10/10 mg/day to 10/40 mg/day.
• The recommended usual starting dose is 10/10 mg/day or 10/20 mg/day.
• After initiation or titration of ezetimibe/simvastatin combination tablet, lipid levels may be analyzed after 2 or more weeks and dosage adjusted, if needed.

Restricted dosing for 10/80 mg

• Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of ezetimibe/simvastatin 10/80 mg should be restricted to patients who have been taking ezetimibe/simvastatin 10/80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.
• Patients who are currently tolerating the 10/80 mg dose of ezetimibe/simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin or statin-based regimen with less potential for the drug-drug interaction.
• Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 10/80 mg dose of ezetimibe/simvastatin, patients unable to achieve their LDL-C goal utilizing the 10/40 mg dose of ezetimibe/simvastatin 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.

Coadministration with other drugs

• Verapamil, diltiazem, or dronedarone: The dose of ezetimibe/simvastatin should not exceed 10/10 mg/day.
• Amiodarone, amlodipine or ranolazine: The dose of ezetimibe/simvastatin should not exceed 10/20 mg/day.
• Bile acid sequestrants: Dosing of Vytostad 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.

Patients with homozygous familial hypercholesterolemia

• The recommended dosage for patients with homozygous familial hypercholesterolemia is ezetimibe/simvastatin 10/40 mg/day in the evening. Ezetimibe/simvastatin combination tablet should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.
• Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of ezetimibe/simvastatin should be reduced by 50% if initiating lomitapide.
• Ezetimibe/simvastatin dosage should not exceed 10/20 mg/day (or 10/40 mg/day for patients who have previously taken simvastatin 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.

Patients with renal impairment/chronic kidney disease

• In patients with mild renal impairment (estimated GFR greater than or equal to 60 ml/min/1.73 m²), no dosage adjustment is necessary. In patients with chronic kidney disease and estimated glomerular filtration rate less than 60 ml/min/1.73 m², the dose of Vytostad is 10/20 mg/day in the evening. In such patients, higher doses should be used with caution and close monitoring.

Geriatric patients

• No dosage adjustment is necessary.
• Use of suitable preparations is recommended when using ezetimibe/simvastatin with dose of 10/40 mg and 10/80 mg.

Usage

• Vytostad is administered orally. It should be taken as a single daily dose in the evening, with or without food.

• 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.
• Hypersensitivity to any of the ingredients.
• Active liver disease or unexplained persistent elevations in hepatic transaminase levels.
• Women who are pregnant or may become pregnant and nursing mothers.

• Thrombocytopaenia, anaemia;
• Anaphylaxis;
• Decreased appetite;
• Sleep disorder, insomnia;
• Dizziness, headache, paraesthesia;
• Abdominal pain, abdominal discomfort, abdominal pain upper, dyspepsia, flatulence, nausea, vomiting, abdominal distension, diarrhea, dry mouth, gastroesophageal reflux disease;
• Constipation, pancreatitis, gastritis;
• Pruritus, rash, urticarial;
• Muscle pain;
• Investigations: Liver function test abnormal;

• The 10/80 mg dose of ezetimibe/simvastatin should be used only in patients who have been taking ezetimibe/simvastatin 10/80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.
• Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, and to report promptly any unexplained muscle pain, tenderness or weakness. If symptoms occur, treatment should be discontinued immediately.
• Periodic CK determinations may be considered in patients starting therapy with Vytostad 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 having had complicated medical histories, including renal insufficiency should be closely monitored while taking Vytostad.
• Vytostad therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected.
• Vytostad therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine, or electrolyte disorders, or uncontrolled epilepsy.
• Drug interactions
  The risk of myopathy and rhabdomyolysis is increased by elevated plasma levels of simvastatin and simvastatin acid. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs that inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy, include itraconazole, ketoconazole, posaconazole, and 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 Vytostad is contraindicated.
  The combined use of Vytostad with gemfibrozil, cyclosporine, or danazol is contraindicated.
  Caution should be used when prescribing fenofibrates and colchicine with Vytostad.
  The benefits of the combined use of Vytostad with the following drugs should be carefully weighed against the potential risks of combinations: other lipid-lowering drugs (fenofibrates or lomitapide), amiodarone, dronedarone, verapamil, diltiazem, amlodipine, or ranolazine, niacin-containing products.
  Temporarily suspend Vytostad in patients taking daptomycin.
• It is recommended that liver function tests be performed before the initiation of treatment with Vytostad. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Vytostad, promptly interrupt therapy.
• Vytostad 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 Vytostad.
• Vytostad is contraindicated in women who are or may become pregnant.
• Nursing women should not take Vytostad.
• When driving vehicles or operating machines, it should be taken into account that dizziness has been reported.