Vastocor10 mg

Vastocor is an HMG-CoA reductase inhibitor (statin) indicated for the following uses:

Established / FDA-approved uses

• Primary hyperlipidemia and mixed dyslipidemia - to reduce elevated total cholesterol, LDL-cholesterol, apolipoprotein B, and triglycerides, and to increase HDL-cholesterol, as an adjunct to diet when response to diet and other non-drug measures alone is inadequate.
• Reduction of the risk of cardiovascular events (myocardial infarction, stroke, revascularization procedures, and cardiovascular death) in patients at high risk of coronary heart disease (established coronary heart disease, diabetes, peripheral vessel disease, or history of stroke), regardless of baseline cholesterol level.
• Homozygous familial hypercholesterolemia - to reduce total and LDL cholesterol, usually as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.
• Heterozygous familial hypercholesterolemia in adolescent patients (10-17 years, at least one year post-menarche in girls) after an adequate trial of diet therapy has failed.
• Hypertriglyceridemia and primary dysbetalipoproteinemia, as an adjunct to diet.

Adjunct / combination therapy

Vastocor is used as an adjunct to diet in all indications above; in familial hypercholesterolemia it may be combined with other lipid-lowering therapies such as LDL apheresis under specialist supervision.

This medicine does not treat existing atherosclerotic plaque directly but reduces the risk of future cardiovascular events through cholesterol lowering; it works best combined with dietary changes, exercise, weight control, and smoking cessation.

Each film-coated tablet contains Simvastatin as the active ingredient, commonly available in strengths of 5 mg, 10 mg, 20 mg, and 40 mg (formulation and available strengths vary by manufacturer). Inactive ingredients typically include binders, fillers, and film-coating agents; refer to the specific product's package insert for a complete list of excipients.

Vastocor is a lipid-lowering agent belonging to the statin class of medicines. It is derived synthetically from a fermentation product of Aspergillus terreus and is chemically an inactive lactone that is hydrolyzed in the body to its active beta-hydroxyacid form. Vastocor works by inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, which lowers LDL-cholesterol and total cholesterol levels and modestly raises HDL-cholesterol. It is taken orally, usually once daily, and is widely used long-term for cardiovascular risk reduction in patients with dyslipidemia.

Vastocor belongs to the therapeutic class of lipid-lowering agents, specifically the HMG-CoA reductase inhibitors (statins).

Mechanism of Action

Simvastatin is an inactive lactone prodrug that is hydrolyzed in vivo to its active beta-hydroxyacid form, simvastatin acid. This active metabolite is a competitive inhibitor of HMG-CoA reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in hepatic cholesterol biosynthesis.

By inhibiting hepatic cholesterol synthesis, Simvastatin reduces intracellular cholesterol, which upregulates hepatic LDL-receptor expression and increases the clearance of LDL-cholesterol from the circulation. It also produces a modest reduction in triglycerides and a modest increase in HDL-cholesterol.

Pharmacokinetics

Simvastatin is well absorbed after oral administration and undergoes extensive first-pass hepatic extraction, making systemic bioavailability of the active form low. It is metabolized predominantly by the CYP3A4 enzyme system, which underlies its significant interactions with CYP3A4 inhibitors. Elimination is mainly via bile and feces, with a smaller fraction excreted renally. Peak lipid-lowering effect is typically seen within 4-6 weeks of starting or adjusting the dose.

Vastocor tablets should be swallowed whole with a glass of water, taken once daily in the evening, with or without food. Do not crush or chew unless the specific formulation permits it. Take at approximately the same time each day for consistent effect. Avoid consuming large quantities of grapefruit juice while taking Vastocor.

Contraindicated Combinations

• Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, cobicistat-containing products, nefazodone) - markedly increase Vastocor plasma levels, substantially raising the risk of myopathy and rhabdomyolysis; concurrent use is contraindicated.
• Gemfibrozil, cyclosporine, and danazol - significantly increase Vastocor exposure and myopathy risk; concurrent use is contraindicated.

Dose-Limiting Combinations

• Verapamil or diltiazem - do not exceed 10 mg Vastocor daily.
• Amiodarone, amlodipine, or ranolazine - do not exceed 20 mg Vastocor daily.

Other Clinically Significant Interactions

• Other fibrates (e.g., fenofibrate) - increased risk of myopathy; use combination cautiously.
• Niacin (lipid-modifying doses, ≥1 g/day) - increased myopathy risk, particularly reported in Chinese patients.
• Colchicine - cases of myopathy and rhabdomyolysis reported with concomitant use.
• Warfarin and other coumarin anticoagulants - Vastocor may potentiate anticoagulant effect; monitor prothrombin time/INR closely when starting or adjusting therapy.
• Grapefruit juice - inhibits intestinal CYP3A4 and can raise Vastocor levels; avoid large quantities (more than about one quart daily).

Most patients tolerate Vastocor well. Reported side effects include:

Common

• Headache
• Gastrointestinal disturbances - abdominal pain, constipation, flatulence, nausea, diarrhea
• Upper respiratory tract infection symptoms
• Mild, transient muscle aches

Less Common / Serious

• Myopathy and rhabdomyolysis - unexplained muscle pain, tenderness, or weakness, especially with fever or malaise, may signal muscle breakdown; report promptly (see Precautions and Warnings).
• Elevated liver transaminases - usually asymptomatic and reversible on discontinuation; rare reports of hepatitis and liver failure.
• New-onset or worsening hyperglycemia/diabetes.
• Peripheral neuropathy (rare).
• Hypersensitivity reactions including rash, pruritus, and rarely angioedema.
• Memory impairment or confusion (rare, generally reversible on stopping the drug).

Vastocor is contraindicated in pregnancy. Cholesterol and other products of cholesterol biosynthesis are essential for fetal development, and safety data along with the mechanism of action suggest a potential for fetal harm when statins are given during pregnancy. If a patient becomes pregnant while taking Vastocor, it should be discontinued immediately and the patient counseled about the potential risk to the fetus. Women of reproductive potential should use effective contraception while taking Vastocor.

Vastocor is also contraindicated during breastfeeding, as it is not known whether clinically significant amounts are excreted in human milk and there is potential for serious adverse effects in the nursing infant. Women who require lipid-lowering therapy while breastfeeding should discuss alternative management with their physician.

Myopathy and Rhabdomyolysis

Vastocor can cause myopathy, and rarely rhabdomyolysis with acute kidney injury, which can be fatal. Risk increases with higher doses, advanced age (65 years or older), female sex, uncontrolled hypothyroidism, renal impairment, and concomitant use of interacting drugs (see Drug Interactions). Patients should be advised to promptly report any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by fever or malaise. Vastocor should be discontinued immediately if myopathy is diagnosed or suspected, or if markedly elevated creatine kinase levels occur.

Hepatic Effects

Persistent elevations in serum transaminases can occur. Liver function tests are recommended before starting Vastocor and if signs or symptoms of liver injury occur (fatigue, anorexia, jaundice, dark urine). Vastocor should be used with caution in patients who consume substantial quantities of alcohol or who have a history of liver disease, and is contraindicated in active liver disease.

Diabetes Mellitus

Statins, including Vastocor, are associated with a small increased risk of elevated blood glucose and new-onset type 2 diabetes; the cardiovascular benefits generally outweigh this risk, but glycemic status should be monitored per usual clinical practice.

Grapefruit Juice

Avoid consuming large quantities of grapefruit juice (more than about one quart daily) while taking Vastocor, as it can increase drug levels via CYP3A4 inhibition.

Females of Reproductive Potential

Effective contraception should be used during treatment given the pregnancy contraindication (see Pregnancy and Lactation).

There is limited specific clinical experience with acute overdosage of Vastocor. No specific antidote is known. If overdose is suspected, seek immediate medical attention or contact a poison control center. Management should be symptomatic and supportive, with general measures to protect the airway and support vital functions; monitoring of liver function and creatine kinase may be advised by the treating physician. Hemodialysis is unlikely to be of significant benefit due to extensive protein binding of the drug.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric Use

Safety and effectiveness of Vastocor in patients younger than 10 years have not been established. In adolescent boys and girls (10-17 years, at least one year post-menarche) with heterozygous familial hypercholesterolemia, Vastocor may be used after an adequate trial of diet therapy has failed, at doses up to 40 mg/day, with periodic growth and development monitoring.

Elderly

Patients 65 years and older are at increased risk of myopathy; a lower starting dose and close monitoring for muscle symptoms are advisable, particularly at higher doses.

Renal Impairment

Patients with severe renal impairment should be started on a lower dose (5 mg once daily) of Vastocor with careful monitoring, given increased systemic exposure.

Hepatic Impairment

Vastocor is contraindicated in patients with active liver disease (see Contraindications).

Asian Patients

Chinese patients taking Vastocor with lipid-modifying doses of niacin may be at increased risk of myopathy; use this combination cautiously.

Vastocor is generally used long-term (often lifelong) for the management of chronic dyslipidemia and cardiovascular risk reduction, as its benefits depend on sustained cholesterol lowering. Treatment duration and continued need should be reassessed periodically by the prescribing physician based on lipid response, tolerability, and overall cardiovascular risk. It should not be stopped abruptly without medical advice, except in situations requiring immediate discontinuation such as suspected myopathy, active liver disease, or pregnancy.

Simvastatin belongs to the drug class of HMG-CoA reductase inhibitors (statins), a group of lipid-lowering agents that also includes atorvastatin, rosuvastatin, pravastatin, and lovastatin.

Simvastatin is hydrolyzed in the liver to its active beta-hydroxyacid form, which competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in the hepatic mevalonate pathway of cholesterol synthesis. Reduced intracellular cholesterol synthesis leads to upregulation of hepatic LDL receptors, increasing clearance of LDL-cholesterol from the blood and lowering circulating LDL-cholesterol and total cholesterol, with modest reductions in triglycerides and modest increases in HDL-cholesterol.

Category X (FDA legacy pregnancy category) - contraindicated in pregnancy.

Vastocor is not indicated for patients younger than 10 years; safety and effectiveness have not been established in this age group. In adolescents aged 10-17 years (girls at least one year post-menarche) with heterozygous familial hypercholesterolemia who have not responded adequately to diet therapy, Vastocor may be started at 10 mg once daily in the evening and titrated as needed up to a maximum of 40 mg/day, with monitoring of growth, development, and hormonal status as clinically indicated.