After a comprehensive review of all available data, the FDA is requesting all statin manufacturers to remove the contraindication in the prescribing information against using statins in pregnant patients. Although statin therapy should be discontinued in most pregnant patients, health care providers should consider the ongoing therapeutic needs of the individual patient, especially patients at very high risk of cardiovascular events during pregnancy, such as patients with homozygous familial hypercholesterolemia or those with established cardiovascular disease. Additionally, breastfeeding is still not recommended in patients taking a statin; health care providers should determine whether it is better to temporarily stop statin therapy while breastfeeding or to continue statin therapy and not have the patient breastfeed. If ongoing statin treatment is necessary, infant formula and other alternatives are available. The FDA expects that removing the contraindication will enable health care providers and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke.
Further information is available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-requests-removal-strongest-warning-against-using-cholesterol-lowering-statins-during-pregnancy.
Note: Use in conjunction with lifestyle modification (eg, diet and exercise). When choosing to initiate therapy and selecting dose intensity, consider the following: Age, baseline LDL-C, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, potential adverse effects, and drug interactions. Simvastatin is considered a moderate-intensity statin at doses of 20 to 40 mg/day (generally reduces LDL-C by ~30% to 49%). If LDL-C must be lowered ≥50%, select an alternative high-intensity statin (atorvastatin or rosuvastatin). Assess response ~1 to 3 months after initiation of therapy or dose adjustment and every 3 to 12 months thereafter. Safety: Dosing limitation: Simvastatin 80 mg/day is not recommended due to increased risk of myopathy. If patient is unable to achieve LDL-C goal with simvastatin 40 mg/day, switch to a high-intensity statin (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Heterozygous familial hypercholesterolemia (alternative agent):
Note: Use of simvastatin should be limited to patients unable to tolerate a high-intensity statin. Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (ACC/AHA [Grundy 2019]; Rosenson 2020a).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Homozygous familial hypercholesterolemia (alternative agent):
Note: Use of simvastatin should be limited to patients unable to tolerate a high-intensity statin. Multiple lipid-lowering therapies may be needed if statin monotherapy is not effective. Referral to a lipid specialist should be considered if treatment goals are not met (ACC/AHA [Grundy 2019]; Rosenson 2020a).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Prevention of atherosclerotic cardiovascular disease:
Note: If LDL-C goal (eg, percent reduction or absolute goal) is not met with the initial dose, may consider up-titration to a maximum of 40 mg/day based on estimated 10-year ASCVD risk (see ACC/AHA ASCVD Risk Estimator Plus online), LDL-C response, and tolerability. If LDL-C goal is not met with maximally tolerated dose, consider switching to a high-intensity statin (atorvastatin or rosuvastatin); additional lipid-lowering therapy may be warranted (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Primary prevention:
Patients without diabetes, 40 to 75 years of age, and LDL-C 70 to 189 mg/dL:
ASCVD 10-year risk 5% to <7.5%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest shared decision-making if ASCVD 10-year risk is 5% to 10%; however, in patients with a baseline LDL-C ≥160 mg/dL, statin therapy is usually recommended (Pignone 2020).
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening to reduce LDL-C by 30% to 49% (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
ASCVD 10-year risk ≥7.5% to <20%:
Note: Depending on baseline LDL-C and presence of risk-enhancing factors, consider statin therapy after shared decision-making with patient. Some experts suggest initiating moderate-intensity statin therapy in most patients if ASCVD 10-year risk is >10% to <20% and LDL-C is >100 mg/dL (Pignone 2020).
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening to reduce LDL-C by 30% to 49%; higher-risk patients with multiple risk-enhancing factors may benefit from high-intensity statin therapy (ie, with atorvastatin or rosuvastatin) to reduce LDL-C by ≥50% (ACC/AHA [Grundy 2019]).
ASCVD 10-year risk ≥20% (alternative agent):
Note: Use of simvastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Patients with diabetes:
Age 40 to 75 years without additional ASCVD risk factors:
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening to reduce LDL-C by 30% to 49% (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
ASCVD 10-year risk ≥20% or multiple ASCVD risk factors (alternative agent):
Note: Use of simvastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Patients with LDL-C ≥190 mg/dL and 20 to 75 years of age (regardless of ASCVD risk estimate or coexisting diabetes mellitus) (alternative agent):
Note: Use of simvastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Secondary prevention in patients with established ASCVD (eg, coronary heart disease, cerebrovascular disease [ischemic stroke or transient ischemic attack], peripheral arterial disease) (alternative agent):
Note: Use of simvastatin should be limited to patients unable to tolerate a high-intensity statin (ACC/AHA [Grundy 2019]; Rosenson 2020a). Patients with high-risk ASCVD may require additional therapies to achieve LDL-C goal (eg, <70 mg/dL or <50 mg/dL if very high risk) (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]; Rosenson 2020b).
Patients unable to tolerate high-intensity therapy (eg, appropriate dose of atorvastatin or rosuvastatin):
Moderate-intensity therapy: Oral: 20 to 40 mg once daily in the evening (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]).
Transplantation, post kidney (alternative agent) (off-label use):
Note: The decision to initiate therapy for primary or secondary prevention is similar to the nontransplant population (see the "Prevention of Atherosclerotic Cardiovascular Disease" indication); however, in patients who are 30 to 39 years of age, some experts suggest statin therapy post kidney transplantation for primary prevention of ASCVD. For primary prevention of ASCVD in patients 18 to 29 years of age, use shared decision-making while considering risks and benefits (Lentine 2022). Certain immunosuppressive drugs can induce or exacerbate hypercholesterolemia; significant drug interactions between statins and immunosuppressant drugs are frequent; some interactions can increase statin serum concentrations and risk of toxicity (eg, myopathy) (AHA [Wiggins 2016]; KDIGO [Tonelli 2014]; Lentine 2022).
Oral: Initial: 20 mg once daily; increase dose based on response, tolerability, and concomitant drugs up to 40 mg once daily (Lentine 2022).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
Initial: No dosage adjustment necessary for any degree of kidney dysfunction. Maximum dose: 40 mg once daily (KDIGO [Tonelli 2013]; Stanifer 2017).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (highly protein bound) (expert opinion):
Note: Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend not initiating a statin in dialysis patients due to lack of benefits shown in this population; however, patients initiated on a statin before progressing to dialysis may continue to receive therapy (KDIGO [Tonelli 2013]).
Daily dosing: No dosage adjustment necessary; maximum dose: 40 mg once daily (KDIGO [Tonelli 2013]; Saltissi 2002; Wanner 1991).
Three times weekly (post dialysis) dosing: 20 mg 3 times weekly after hemodialysis on dialysis days (Suassuna 2007; Yigit 2004).
Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound) (expert opinion):
Note: KDIGO guidelines recommend not initiating a statin in dialysis patients due to lack of benefits shown in this population; however, patients initiated on a statin before progressing to dialysis may continue to receive therapy (KDIGO [Tonelli 2013]).
No dosage adjustment necessary; maximum dose: 40 mg once daily (KDIGO [Tonelli 2013]; Saltissi 2002).
CRRT: Unlikely to be significantly dialyzed (highly protein bound) (expert opinion): No dosage adjustment necessary; maximum dose: 40 mg once daily (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): Unlikely to be significantly dialyzed (highly protein bound) (expert opinion): No dosage adjustment necessary; maximum dose: 40 mg once daily (expert opinion).
Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.
(For additional information see "Simvastatin: Pediatric drug information")
Note: A lower, conservative dosing regimen may be necessary in patient populations predisposed to myopathy including patients of Chinese descent or those concurrently receiving other lipid-lowering agents (eg, niacin, fibric acid derivatives), amiodarone, amlodipine, diltiazem, dronedarone, ranolazine, verapamil (see the following conservative, maximum adult doses). Dosage should be individualized according to the baseline LDL-C level, the recommended goal of therapy, and patient response; adjustments should be made at intervals of 4 weeks. Lifestyle changes are recommended to be implemented for at least 6 to 12 months before beginning pharmacotherapy (AACE [Jellinger 2017]).
Hyperlipidemia or heterozygous familial hypercholesterolemia (HeFH) and nonfamilial hypercholesterolemia: Note: Limited data available for nonfamilial hypercholesterolemia or other forms of non-HeFH hyperlipidemia.
Begin treatment if, after adequate trial (6 to 12 months) of intensive lifestyle modification emphasizing body weight normalization and diet, the following are present (AACE [Jellinger 2017]):
LDL-C ≥190 mg/dL or
LDL-C remains ≥160 mg/dL and two or more cardiovascular risk factors: Family history of premature atherosclerotic cardiovascular disease (<55 years of age), overweight, obesity, or other elements of insulin resistance syndrome or
LDL-C ≥130 mg/dL and diabetes mellitus (Daniels 2008; NHLBI 2011).
Therapy may also be considered for children 8 to 9 years of age meeting the above criteria or for children with diabetes mellitus and LDL-C ≥130 mg/dL (Daniels 2008).
Children ≥4 years and <10 years: Very limited data available: Oral: Initial: 5 mg once daily in the evening increasing to 10 mg once daily after 4 weeks and to 20 mg once daily after another 4 weeks as tolerated; maximum daily dose: 20 mg/day; most experience is with children at least 8 years of age; in trials, the youngest reported patient was 4 years of age (Ducobu 1992; García-de-la-Puente 2009; Stefanutti 1999; Vuorio 2017).
Children ≥10 years and Adolescents: Oral: Initial: 10 mg once daily in the evening increasing to 20 mg once daily after 6 weeks and to 40 mg once daily after another 6 weeks as tolerated; maximum daily dose: 40 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Muscle symptoms (potential myopathy): Children ≥4 years and Adolescents: Discontinue use until symptoms can be evaluated; check CPK level; based on experience in adult patients, also evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution (symptoms and any associated CPK abnormalities), resume the original or consider a lower dose of simvastatin and retitrate. If muscle symptoms recur, discontinue simvastatin use. After muscle symptom resolution, may then reinitiate a different statin at an initial low dose; gradually increase if tolerated. Based on experience in adult patients, if muscle symptoms or elevated CPK persists for 2 months in the absence of continued statin use, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (NHLBI 2011; Stone 2013).
There are no pediatric specific recommendations. Simvastatin does not undergo significant renal excretion. Based on experience in adult patients with mild-to-moderate renal impairment, no dosage adjustment necessary; in severe impairment, use with caution.
Contraindicated in patients with active liver disease, including unexplained persistent elevations in hepatic transaminases.
Refer to adult dosing.
Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (ACC/AHA [Stone 2014]).
Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution, resume the original or lower dose of simvastatin. If muscle symptoms recur, discontinue simvastatin use. After muscle symptom resolution, may then use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (ACC/AHA [Stone 2014]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suspension, Oral:
FloLipid: 20 mg/5 mL (150 mL); 40 mg/5 mL (150 mL) [contains ethylparaben, methylparaben, propylene glycol, propylparaben]
Generic: 20 mg/5 mL (75 mL [DSC])
Tablet, Oral:
Zocor: 5 mg [DSC], 10 mg, 20 mg, 40 mg, 80 mg [DSC]
Generic: 5 mg, 10 mg, 20 mg, 40 mg, 80 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Zocor: 10 mg, 20 mg, 40 mg
Generic: 5 mg, 10 mg, 20 mg, 40 mg, 80 mg
Oral:
Suspension: Administer in the evening on an empty stomach. Shake well for at least 20 seconds before administering dose.
Tablets: Administered without regard to meals. Administer in the evening for maximal efficacy.
Oral: May be taken without regard to meals. Administration with the evening meal or at bedtime has been associated with somewhat greater LDL-C reduction
Heterozygous familial hypercholesterolemia: To reduce elevated total cholesterol (total-C), LDL-C, apoB, and triglyceride levels, and to increase HDL-C in patients with primary hypercholesterolemia.
Heterozygous familial hypercholesterolemia (pediatrics): To reduce total-C, LDL-C, and apoB levels in boys and postmenarche girls 10 to 17 years of age with heterozygous familial hypercholesterolemia with either LDL-C ≥190 mg/dL, LDL-C ≥160 mg/dL with positive family history of premature cardiovascular disease (CVD), or LDL-C ≥160 mg/dL with 2 or more other CVD risk factors.
Homozygous familial hypercholesterolemia: To reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.
Prevention of atherosclerotic cardiovascular disease:
Primary prevention of atherosclerotic cardiovascular disease: To reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, and angina in adults without a history of coronary heart disease (CHD) but who have multiple CHD risk factors.
Secondary prevention in patients with established atherosclerotic cardiovascular disease: To reduce the risk of MI, stroke, revascularization procedures, and angina in patients with a history of CHD.
Transplantation, post kidney
Simvastatin may be confused with atorvastatin, nystatin, pitavastatin
Zocor may be confused with Cozaar, Lipitor, Zoloft, ZyrTEC
Cardin [Poland] may be confused with Cardem brand name for celiprolol [Spain]; Cardene brand name for nicardipine [US, Great Britain, Netherlands]
Statins are associated with increased serum transaminases and hepatotoxicity (Ref). Asymptomatic transient or persistent increases both <3 or >3 times the ULN in serum transaminases may occur with all statins; the increase in alanine aminotransferase (ALT) is typically greater than the increase in aspartate aminotransferase (AST) (Ref). Acute hepatotoxicity, rarely presenting as a drug-induced autoimmune hepatitis, has been documented (Ref).
Upon dose reduction or discontinuation, transaminase levels return to or near pretreatment levels; although, mild elevations resolve with continued use in some cases (Ref). In patients with acute hepatotoxicity, resolution of symptoms usually occurs within 1 to 2 months; however, some cases may not normalize until 5 months after discontinuation (Ref). Chronic liver injury (defined as liver biochemical or histological abnormalities that persisted for 6 months or more after onset) has been reported (Ref).
Mechanism: Unknown; inhibition of the CYP450 system, leading to increased plasma concentrations of statins has been postulated (Ref). Minor toxic intermediate metabolites may cause mild increases in ALT (Ref).
Onset: Varied; duration of therapy prior to hepatotoxicity ranges from 1 month to several years (Ref). Most cases occur within the first 3 months of initiation or dose escalation (Ref).
Risk factors:
• Higher doses may increase the risk of liver injury (Ref)
• Concurrent medication with statin drug-drug interactions or hepatotoxic properties (Ref)
• Hepatotoxicity is more commonly associated with atorvastatin than pravastatin, rosuvastatin, and simvastatin (Ref). Fluvastatin is associated with the greatest risk of developing hepatotoxicity (Ref).
• Cross-reactivity between different statins and the susceptibility to hepatotoxicity is unknown as data have shown conflicting results (Ref).
• Chronic hepatitis B and alcohol consumption are independent risk factors for hepatic aminotransferase elevation associated with statins in patients 80 years of age or older (Ref).
Statins are associated with several muscle-related effects, including:
• Myalgia (muscle symptoms without significant creatine kinase [CK] elevations; also known as statin-associated muscle symptoms) (Ref)
• Myopathy (defined as unexplained muscle pain or weakness accompanied by a CK concentration >10 times the ULN) (Ref)
• Rhabdomyolysis (CK >40 times the ULN) (Ref) often with acute renal failure secondary to myoglobinuria (Ref)
• Immune-mediated necrotizing myopathy (IMNM) (elevated CK plus the presence of antibodies against HMG-CoA) (Ref)
Mechanism: Uncertain; alterations in the mevalonate pathway and changes in the electrical and structural characteristics of the sarcolemma related to calcium ion flux possibly contribute (Ref). Decreased ubiquinone, which is essential for energy production in skeletal muscle, may also contribute (Ref). Myopathy/rhabdomyolysis risk is related to circulating active drug concentrations (Ref). IMNM is considered an immune-mediated process; autoantibodies against HMG-CoA reductase (anti-HMG-CoA) have been identified (Ref).
Onset: Delayed; often presents within a few months after starting therapy (highest risk within first year of use), when the dose of the statin is increased, or when introducing an interacting drug (Ref). Muscle symptoms often appear more promptly when patients are reexposed to the same statin (Ref). Duration of statin use prior to development of IMNM is ~2 to 3 years (Ref).
Risk factors:
• First year of therapy (Ref)
• Dose increase (for myopathy and rhabdomyolysis, but not IMNM) (Ref)
• Addition of an interacting drug (eg, concurrent use of medications associated with myopathy [eg, gemfibrozil] or concurrent use of strong CYP3A4 inhibitors) (Ref)
• Older patients (Ref)
• Hypothyroidism (Ref)
• Preexisting muscle disease (Ref)
• Kidney impairment, especially with simvastatin 80 mg/day (Ref)
• Females (Ref)
• Low body mass index (Ref)
• Heavy exercise (Ref)
• Surgery (Ref)
• Higher HMG-COA reductase inhibitory activity (Ref), rosuvastatin > atorvastatin > simvastatin > pravastatin ≈ lovastatin (Ref)
• Asian population: Data are conflicting regarding increased susceptibility to myopathy with simvastatin in patients of Chinese origin (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reaction incidence reported in adults.
1% to 10%:
Cardiovascular: Atrial fibrillation (6%), edema (≤3%)
Dermatologic: Eczema (5%)
Gastrointestinal: Abdominal pain (7%), constipation (7%), gastritis (5%), nausea (5%)
Genitourinary: Cystitis (interstitial; Huang 2015)
Hepatic: Increased serum transaminases (≤2%)
Nervous system: Headache (3% to 7%), vertigo (5%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (>3 × normal: 5%), myalgia (4%) (table 1)
|
Drug (Simvastatin) |
Placebo |
Population |
Dosage Form |
Number of Patients (Simvastatin) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
4% |
3% |
Adults |
Tablets |
2,221 |
2,223 |
Respiratory: Bronchitis (7%), upper respiratory infection (9%)
Miscellaneous: Swelling (≤3%)
Frequency not defined:
Dermatologic: Skin rash
Endocrine & metabolic: Increased gamma-glutamyl transferase
Gastrointestinal: Diarrhea, dyspepsia, flatulence
Hepatic: Increased serum alkaline phosphatase
Nervous system: Asthenia
Postmarketing:
Cardiovascular: Flushing, vasculitis
Dermatologic: Alopecia, changes in nails, changes of hair, cutaneous nodule, erythema multiforme, lichen planus, pruritus, skin discoloration, skin photosensitivity (Morimoto 1995), Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria, xeroderma
Endocrine & metabolic: Elevated glycosylated hemoglobin, increase in fasting plasma glucose
Gastrointestinal: Dry mucous membranes, dysgeusia (Tuccori 2011), pancreatitis (Johnson 2006), vomiting
Genitourinary: Erectile dysfunction
Hematologic & oncologic: Anemia, eosinophilia (de las Marinas Alvarez 2018), hemolytic anemia, increased erythrocyte sedimentation rate, leukopenia, positive ANA titer, purpuric disease, thrombocytopenia (Groneberg 2001)
Hepatic: Autoimmune hepatitis (Russo 2014), hepatic failure, hepatitis, jaundice
Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction
Immunologic: Dermatomyositis (Chemello 2017)
Nervous system: Chills, cognitive dysfunction (including amnesia, confusion, forgetfulness, memory impairment) (Suraweera 2016), depression, dizziness, malaise, paresthesia, peripheral neuropathy (Phan 1995)
Neuromuscular & skeletal: Arthralgia (Campion 2008), arthritis, immune-mediated necrotizing myopathy (Essers 2019), lupus-like syndrome (Ahmad 2000), muscle cramps, myopathy (Newman 2019), polymyalgia rheumatica, rhabdomyolysis (Kariyanna 2019)
Respiratory: Dyspnea, interstitial pulmonary disease (De Groot 1996)
Miscellaneous: Fever
Hypersensitivity to simvastatin or any component of the formulation; acute liver disease or decompensated cirrhosis; concomitant use of strong CYP3A4 inhibitors (select azole antifungals [eg, itraconazole, ketoconazole, posaconazole, voriconazole], select macrolide antibiotics [eg, erythromycin and clarithromycin], select HIV protease inhibitors [eg, nelfinavir, ritonavir, darunavir/ritonavir], select hepatitis C virus protease inhibitors [eg, boceprevir, telaprevir], cobicistat-containing products, and nefazodone), cyclosporine, danazol, or gemfibrozil.
Canadian labeling: Additional contraindications (not in the US labeling): Persistent elevated transaminases; breastfeeding; pregnancy.
Concerns related to adverse effects:
• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported; however, the benefits of statin therapy far outweigh the risk of dysglycemia.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients who consume large amounts of ethanol and/or have a history of liver disease; may require dosage adjustment in some patients with hepatic impairment.
• Myasthenia gravis: May rarely worsen or precipitate myasthenia gravis (MG); monitor for worsening MG if treatment is initiated (AAN [Narayanaswami 2021]).
• Renal impairment: Use with caution in patients with severe renal impairment (creatinine clearance not defined); monitor closely.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Special Populations:
• Elderly: Use with caution in patients ≥65 years of age; these patients are predisposed to myopathy.
• Surgical patients: Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period for noncardiac and cardiac surgery (ACC/AHA [Fleisher 2014]; ACC/AHA [Hillis 2011]). Perioperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Substrate of CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Amiodarone: May increase serum concentrations of the active metabolite(s) of Simvastatin. Amiodarone may increase the serum concentration of Simvastatin. Management: Consider using a non-interacting statin (pravastatin) in patients on amiodarone. If combined, limit the adult simvastatin dose to 20 mg daily and monitor for evidence of simvastatin toxicities (eg, myalgia, liver function test elevations, rhabdomyolysis). Risk D: Consider therapy modification
AmLODIPine: May increase the serum concentration of Simvastatin. Management: Dose of simvastatin should not exceed 20 mg daily if coadministering with amlodipine. If coadministering with simvastatin and amlodipine, close laboratory and clinical monitoring for signs and symptoms of rhabdomyolysis is warranted. Risk D: Consider therapy modification
Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Risk C: Monitor therapy
Bempedoic Acid: May increase the serum concentration of Simvastatin. Management: Avoid coadministration of bempedoic acid with simvastatin doses greater than 20 mg due to the potential for increased simvastatin concentrations and simvastatin-related myopathy. Risk D: Consider therapy modification
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Avoid use of bezafibrate and HMG-CoA reductase inhibitors (statins) unless strictly indicated due to the increased of muscle toxicity (including rhabdomyolysis). In patients who may be predisposed to myopathy, concomitant use is contraindicated. Risk D: Consider therapy modification
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Risk D: Consider therapy modification
Ciprofloxacin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Ciprofloxacin (Systemic) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Colchicine. Risk C: Monitor therapy
CycloSPORINE (Systemic): May increase the serum concentration of Simvastatin. Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Simvastatin. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Simvastatin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Simvastatin. Risk X: Avoid combination
CYP3A4 Inhibitors (Weak): May increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Dabigatran Etexilate: Simvastatin may enhance the anticoagulant effect of Dabigatran Etexilate. Risk C: Monitor therapy
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Danazol: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
DAPTOmycin: Simvastatin may enhance the adverse/toxic effect of DAPTOmycin. Risk X: Avoid combination
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Digoxin: Simvastatin may increase the serum concentration of Digoxin. Risk C: Monitor therapy
DilTIAZem: Simvastatin may decrease the serum concentration of DilTIAZem. DilTIAZem may increase the serum concentration of Simvastatin. Management: Avoid concurrent use of diltiazem with simvastatin when possible. If used together, limit adult doses to simvastatin 10 mg daily and diltiazem 240 mg per day; monitor closely for signs of simvastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Dronedarone: May increase serum concentrations of the active metabolite(s) of Simvastatin. Dronedarone may increase the serum concentration of Simvastatin. Management: Carefully consider the potential risks and benefits of this combination. If coadministered, limit adult simvastatin dose to 10 mg daily, and monitor closely for signs of simvastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Elbasvir and Grazoprevir: May increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Encorafenib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Erythromycin (Systemic): May increase serum concentrations of the active metabolite(s) of Simvastatin. Erythromycin (Systemic) may increase the serum concentration of Simvastatin. Risk X: Avoid combination
Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors (Statins). This applies to atorvastatin, lovastatin and simvastatin. Risk C: Monitor therapy
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fosamprenavir: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Fostamatinib: May increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Fostemsavir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest possible starting statin dose and monitor patients closely for statin-related adverse effects (eg, muscle aches and pains) during coadministration with fostemsavir. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Gemfibrozil may increase the serum concentration of Simvastatin. Concentrations of the active simvastatin acid metabolite may also be increased by gemfibrozil. Risk X: Avoid combination
Glecaprevir and Pibrentasvir: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Itraconazole: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Lacidipine: May increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Lanthanum: HMG-CoA Reductase Inhibitors (Statins) may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors (eg, statins) at least two hours before or after lanthanum. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Lercanidipine: May increase the serum concentration of Simvastatin. Management: Administer lercanidipine in the morning and simvastatin in the evening in patients receiving these drugs in combination. Risk D: Consider therapy modification
Letermovir: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Levamlodipine: May increase the serum concentration of Simvastatin. Management: Limit simvastatin dose to 20 mg daily and monitor closely for signs and symptoms of rhabdomyolysis (eg, creatinine phosphokinase, muscle aches and pains) if coadministering with levamlodipine. Risk D: Consider therapy modification
Lomitapide: May increase serum concentrations of the active metabolite(s) of Simvastatin. Lomitapide may increase the serum concentration of Simvastatin. Management: Reduce the recommended simvastatin dose by 50%. Generally, limit the maximum adult simvastatin dose to 20 mg/day. A 40 mg/day dose can be considered in patients who previously received 80 mg/day for at least a year without evidence of muscle toxicity. Risk D: Consider therapy modification
Lonafarnib: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Niacin: May enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Niacin may increase the serum concentration of Simvastatin. Management: Avoid this combination in Chinese patients; some non-US labeling state this combination is not recommended in any Asian patients. If coadministered, consider simvastatin dose reductions and monitor closely for signs and symptoms of muscle toxicity. Risk D: Consider therapy modification
Nirmatrelvir and Ritonavir: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Pacritinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Ranolazine: May increase the serum concentration of Simvastatin. Management: Carefully consider the potential benefits and risks of this combination. Limit simvastatin to 20 mg daily if coadministered, and monitor closely for signs and symptoms of myopathy or rhabdomyolysis. Risk D: Consider therapy modification
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Risk X: Avoid combination
Repaglinide: HMG-CoA Reductase Inhibitors (Statins) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
Roxadustat: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor therapy
Rupatadine: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors (Statins). Specifically, the risk for increased CPK and/or other muscle toxicities may be increased. Risk C: Monitor therapy
Simeprevir: May increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Spironolactone: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
St John's Wort: May decrease serum concentrations of the active metabolite(s) of HMG-CoA Reductase Inhibitors (Statins). Management: Consider avoiding the concomitant administration of St John's Wort with atorvastatin, lovastatin and simvastatin in order to avoid the potential for decreased effects statins. If coadministered, monitor for decreased statin efficacy. Risk D: Consider therapy modification
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Ticagrelor: May increase the serum concentration of Simvastatin. Management: Avoid using doses of simvastatin greater than 40 mg/day with ticagrelor. Monitor for increased systemic effects of simvastatin in patients receiving concurrent ticagrelor. Risk D: Consider therapy modification
Tipranavir: May increase the serum concentration of Simvastatin. Risk X: Avoid combination
Trabectedin: HMG-CoA Reductase Inhibitors (Statins) may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Risk C: Monitor therapy
Treosulfan: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Verapamil: May increase serum concentrations of the active metabolite(s) of Simvastatin. Verapamil may increase the serum concentration of Simvastatin. Management: Carefully consider the potential risks and benefits of this combination. If coadministered, limit adult simvastatin dose to 10 mg daily, and monitor closely for signs of simvastatin toxicity (eg, myositis, rhabdomyolysis). Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors (Statins) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with voxilaprevir and monitor patients for increased statin effects/toxicities. Avoid concomitant use of voxilaprevir with rosuvastatin or pitavastatin, and limit pravastatin doses to 40 mg daily. Risk D: Consider therapy modification
Simvastatin serum concentration may be increased when taken with grapefruit juice. Management: Avoid combination.
Adequate contraception is recommended if an HMG-CoA reductase inhibitor (statin) is required in patients who may become pregnant (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]). Nonhormonal contraception is preferred for patients at high risk of atherosclerotic cardiovascular disease and those with familial hypercholesterolemia (Balla 2020). Patients planning to become pregnant should discuss their lifetime risk of cardiovascular disease, as well as risks and benefits of statin therapy with their health care team (CCS [Pearson 2021]). When appropriate, statins can be discontinued 1 to 2 months prior to conception (AHA/ACC [Grundy 2019]).
When a statin is needed in a patient of reproductive potential, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred to limit placental transfer (CCS [Pearson 2021]).
In healthy pregnancies, changes in lipid synthesis occur that are required for normal placental and fetal growth. Low-density lipoprotein cholesterol and triglycerides increase as pregnancy progresses and decline postpartum. HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Therefore, based on the mechanism of action, in utero exposure may cause fetal harm (Lecarpentier 2012); however, data from available studies have not shown an increased risk of major congenital anomalies following first trimester exposure (Bateman 2015; Chang 2021; Vahedian-Azimi 2021a). Additional data are needed to evaluate other pregnancy outcomes, such as miscarriage (Vahedian-Azimi 2021b).
Because there is potential for fetal harm, statins should be discontinued once pregnancy is recognized (AHA/ACC [Grundy 2019]; Brunham 2018). If lipid-lowering therapy during pregnancy is required, it should be individualized based on the therapeutic needs of the patient, considering the lifetime risk of untreated disease, use of nonstatin therapies, as well as the known risks and benefits of statins. Based on limited data, when a statin is needed in a pregnant patient, a more hydrophilic option (eg, pravastatin, rosuvastatin) may be preferred. Lipophilic statins (eg, atorvastatin, fluvastatin, lovastatin, simvastatin, pitavastatin) may be more likely to cross the placenta and increase the risk of congenital malformations (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Lecarpentier 2012).
Additional data are needed to clarify the role of statins for the prevention of atherosclerotic cardiovascular disease in at-risk pregnant patients (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]; Parikh 2021).
It is not known if simvastatin is present in breast milk.
HMG-CoA reductase inhibitors (statins) decrease the synthesis of cholesterol and substances derived from cholesterol. Normal concentrations of cholesterol in breast milk are required for infant development (Holmsen 2017; Lecarpentier 2012). Due to the potential for adverse events in the breastfed infant, breastfeeding is not recommended by the manufacturer. Available guidelines recommend resuming statin therapy once breastfeeding is completed (AHA/ACC [Grundy 2019]; CCS [Pearson 2021]).
Generally, patients should be placed on a standard cholesterol-lowering diet and other lifestyle modifications for 3 to 6 months prior to the initiation of drug therapy. The diet should be continued during drug therapy. However, for patients with advanced risk factors (eg, known coronary heart disease), drug therapy may be initiated concurrently with diet modification. Simvastatin serum concentration may be increased when taken with grapefruit juice; avoid concurrent intake of grapefruit juice.
Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).
ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Grundy 2019]; ACC/AHA [Stone 2014]):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (AST and ALT); measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation. Monitor for signs and symptoms of myopathy or rhabdomyolysis (especially in patients with renal impairment).
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Manufacturer's labeling: Consider neuromuscular and serologic testing if immune-mediated necrotizing myopathy is suspected.
Treatment goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to clinical practice guidelines for specific treatment goals.
Simvastatin is a methylated derivative of lovastatin that acts by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).
Onset of action: >3 days.
Peak effect: 2 weeks.
LDL-C reduction: 20 to 40 mg/day: 35% to 41%.
Average HDL-C increase: 5% to 15%.
Average triglyceride reduction: 7% to 30%.
Absorption: Although 85% is absorbed following administration, <5% reaches the general circulation due to an extensive first-pass effect.
Protein binding: ~95%.
Metabolism: Hepatic via CYP3A4; extensive first-pass effect.
Bioavailability: <5%.
Half-life elimination: Unknown.
Time to peak: 1.3 to 2.4 hours.
Excretion: Feces (60%); urine (13%).
Altered kidney function: Higher systemic exposure may be achieved in patients with severe renal insufficiency.
Older adult: Mean plasma level of HMG-CoA reductase inhibitory activity is increased approximately 45%.
Tablets (Simvastatin Oral)
5 mg (per each): $0.02 - $2.81
10 mg (per each): $0.02 - $2.82
20 mg (per each): $0.04 - $4.92
40 mg (per each): $0.05 - $4.92
80 mg (per each): $0.06 - $4.92
Tablets (Zocor Oral)
10 mg (per each): $5.82
20 mg (per each): $10.15
40 mg (per each): $10.15
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