Simvastatin

Simvastatin reduces mortality and coronary/cerebrovascular events and revascularization risk in defined high-risk adults with coronary, cerebrovascular or peripheral vascular disease and/or diabetes. It is used with diet for primary hyperlipidemia, HeFH, primary dysbetalipoproteinemia and hypertriglyceridemia; adult HoFH use is adjunctive to other LDL-lowering therapies.

The pediatric approval is for LDL reduction with diet in HeFH from age 10 years. Other pediatric lipid disorders and younger ages are not established uses. Current AHA/ACC guidance combines risk assessment, LDL/non-HDL goals and percentage reduction; if high-intensity therapy is required or goals remain unmet at 40 mg, the label directs an alternative LDL-lowering treatment.

Take orally once daily in the evening. Adults: the recommended range is 20–40 mg daily. HeFH from age 10: 10–40 mg daily. Reassess LDL-C as early as 4 weeks after initiation and adjust according to response, tolerance and interaction limits. A missed dose may be taken as soon as possible; do not double the next dose.

The usual recommended maximum is 40 mg daily. An 80 mg regimen is reserved for patients already taking 80 mg chronically, such as for at least 12 months, without muscle toxicity; do not start or titrate a patient to 80 mg. If an interacting drug is needed in someone on 80 mg, select another statin. Zocor no longer markets its 80 mg strength.

For severe renal impairment with creatinine clearance 15–29 mL/min, start at 5 mg once daily. Zocor’s 5 mg strength is no longer marketed, so select an appropriate alternative simvastatin tablet product. Mild/moderate renal impairment has no recommended dose adjustment, but all renal impairment increases muscle-toxicity risk. The cited dosing section does not establish a routine regimen for CrCl below 15.

Apply the exact co-medication cap even when the usual adult dose would be higher. Lomitapide’s legacy 40 mg exception is restricted to patients previously tolerating chronic 80 mg; it is not a new-start regimen.

The reviewed regimens refer to oral tablets. Marketed Zocor strengths are 10, 20 and 40 mg; generic labels also describe 5 and 80 mg tablets. Strength availability does not override dose restrictions. Liquid or combination products require their own label and administration/storage instructions.

Strong CYP3A4 inhibitor coadministration, cyclosporine, danazol or gemfibrozil, acute liver failure/decompensated cirrhosis, and hypersensitivity to simvastatin or ingredients are contraindications. Pregnancy is no longer an absolute U.S. statin contraindication; the separate pregnancy risk assessment remains essential.

The reviewed simvastatin tablet labels do not carry an FDA boxed warning. This does not diminish the important muscle, interaction and hepatic precautions, including the restriction on 80 mg dosing.

Common reported trial events include headache, abdominal discomfort, constipation and nausea; upper respiratory infection was also commonly recorded. Serious postmarketing events include hepatic failure, immune-mediated myopathy and severe hypersensitivity. New or worsening myasthenia gravis and generally reversible cognitive symptoms have also been reported; spontaneous reports do not establish frequency or causation.

Strong CYP3A4 inhibitors include selected azoles (itraconazole, ketoconazole, posaconazole, voriconazole), macrolides (erythromycin, clarithromycin), boosted protease-inhibitor/cobicistat products and nefazodone. Suspend simvastatin for an unavoidable short course of a strong inhibitor. Cyclosporine, danazol and gemfibrozil are also contraindicated. Confirm the exact antiviral regimen rather than assuming every antiviral has the same interaction.

Observe the cardiac-drug and lomitapide caps above. Review temporary suspension during daptomycin treatment. Other fibrates, colchicine and lipid-modifying niacin doses (≥1 g/day) need benefit/risk review and muscle surveillance. Simvastatin with lipid-modifying niacin is not recommended in Chinese patients. Avoid grapefruit juice.

Obtain INR before initiating simvastatin with a coumarin anticoagulant, then check sufficiently often after starting, dose changes or discontinuation until stable. Simvastatin can increase digoxin concentrations; monitor levels when simvastatin is initiated.

Discontinue when pregnancy is recognized in most patients. FDA removed the blanket statin pregnancy contraindication in 2021 to permit individualized decisions for very high-risk patients, including HoFH or established cardiovascular disease. Available observational data do not show a clear increase in major malformations after adjustment, but miscarriage risk is uncertain and fetal harm remains possible. Discuss any exceptional continuation with specialists.

Breastfeeding is not recommended while taking simvastatin because of potential effects on infant cholesterol metabolism and limited infant safety evidence. Discuss temporarily withholding lipid treatment or an alternative feeding plan when continued therapy is necessary.

HeFH approval starts at age 10; trial girls were at least one year post-menarche. Do not impose an unverified approval for other pediatric lipid disorders or doses above 40 mg. Older adults have greater myopathy risk; choose doses cautiously and assess concomitant disease, renal function and medicines.

Monitor renal impairment for muscle toxicity and use the severe-renal starting-dose rule. Acute liver failure or decompensated cirrhosis is contraindicated; substantial alcohol use or liver history warrants assessment. The label reports greater myopathy risk in Chinese patients, particularly with niacin combinations; monitor and avoid the stated combination.

Simvastatin is hydrolyzed to simvastatin acid, which inhibits HMG-CoA reductase. Increased hepatic LDL-receptor expression promotes LDL uptake and lowers circulating LDL-C. Maximal LDL reduction is usually reached by about 4 weeks.

Extensive hepatic first-pass extraction leaves low systemic availability (below 5%). Simvastatin and its active acid are about 95% protein bound. CYP3A4 metabolism and OATP1B1 transport help explain exposure interactions. Active/total inhibitor peaks occur around 1.3–2.4 hours; labeled radiolabel recovery is mainly fecal, with a smaller urinary component.

Protein binding

About 95%

Metabolism / transport

CYP3A4 / OATP1B1

Assess baseline lipid status, cardiovascular risk, relevant organ function, muscle history, hypothyroidism and interacting medicines. Consider liver enzymes before therapy and thereafter for clinical indications. Follow LDL response from about 4 weeks onward. Investigate symptoms with CK and related testing as clinically appropriate; avoid turning the label into a universal schedule for asymptomatic CK testing.

The 2026 AHA/ACC guideline replaces the 2018 cholesterol guideline and uses PREVENT-ASCVD for relevant primary-prevention risk assessment, with individualized lipid goals and additional risk information. This monograph does not reproduce the full eligibility algorithm; select treatment intensity and alternatives with the applicable guideline and patient-specific risk.

Take in the evening, avoid grapefruit juice and check before starting any new drug or supplement. Report unexplained muscle pain/weakness, especially with fever or malaise, and jaundice or dark urine. Notify the clinician about pregnancy plans or a recognized pregnancy. Suspected overdose requires poison-center advice; no specific simvastatin antidote is known.

Zocor 20 mg is a tan, oval tablet marked MSD 740 on one side, plain on the other. Example bottle of 30: NDC 78206-181-01. It is manufactured for Organon; generic tablet appearance and NDC differ.

Zocor currently markets 10, 20 and 40 mg tablets; its 5 and 80 mg strengths are no longer marketed. The reviewed generic label describes 5, 10, 20, 40 and 80 mg tablet strengths. The presence of an 80 mg strength is not permission to initiate it. This page does not supply liquid or combination-product instructions.

For the reviewed Zocor product, store between 5°C and 30°C. Generic tablet storage instructions can differ; follow the dispensed label and keep away from children. Do not apply this tablet storage range to a separately formulated oral suspension.