1.1. Adults

HMG-CoA reductase inhibitors, or statins, are lipid-lowering agents that competitively inhibit HMG-CoA reductase, the enzyme that catalyzes cholesterol biosynthesis. Inhibiting this enzyme results in decreases in total cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and apoprotein B (Apo B), increases in high-density lipoprotein cholesterol (HDL-C), as well as increases in the number of LDL receptors on hepatic and extrahepatic tissues. Clinical and epidemiologic studies have documented that low HDL-C, high LDL-C and elevated TG augment atherosclerosis development and are risk factors for cardiovascular disease, while higher HDL-C levels and lower LDL-C concentrations are associated with reduced cardiovascular risk1-14.

Statins are FDA-approved to manage hyperlipidemia (including hypercholesterolemia, mixed dyslipidemia, hypertriglyceridemia, and primary dysbetalipoproteinemia) in adults, treat homozygous familial hypercholesterolemia in adults, reduce the risk of coronary heart disease mortality and cardiovascular events in patients at high risk for coronary events, slow the progression of coronary atherosclerosis in patients with coronary artery disease by reducing total cholesterol and LDL-C levels, provide primary prevention of coronary artery disease in patients with risk factors for coronary artery disease but without symptomatic cardiovascular disease, promote secondary prevention of coronary events in patients with cardiovascular disease, and treat adolescents with heterozygous familial hypercholesterolemia unresponsive to diet therapy1-14.

Statin combination therapies are FDA-approved to manage primary hyperlipidemia/mixed dyslipidemia and homozygous familial hypercholesterolemia (Vytorin®) when monotherapy is deemed inadequate. Caduet® is FDA-approved in those patients requiring both amlodipine and atorvastatin1,2,15,16. In 2021 the combination product Roszet® (ezetimibe/ rosuvastatin) was approved for the management of homozygous familial hypercholesterolemia alone or in combination with other LDL-C lowering therapies and primary nonfamilial hyperlipidemia1,2,17.

Higher statin doses may be necessary in patients who respond poorly to initial prescribed amounts. Doses may be escalated incrementally every four weeks at minimum, based on patient need and tolerance, to the maximum recommended dose. However, the FDA now recommends limiting use of the highest simvastatin dose (80 mg) to only those patients who have been taking the dose for 12 months or more without evidence of myopathy, due to greater risks for muscle injury compared to lower simvastatin doses or other statins1,2,11,12.

Recommended adult statin maintenance doses as mono- and combination therapy should not exceed the maximum doses listed in Tables 1 and 2.

Table 1. HMG-CoA Reductase Inhibitor Monotherapy – Maximum Recommended Adult Dosages1-14
Drug Dosage Form/Strength Maximum Recommended Dosage
atorvastatin (Lipitor®, generic) 10 mg, 20 mg, 40 mg, 80 mg tablets
  • 80 mg once daily
  • concurrent administration with nelfinavir:
    • 40 mg once daily
  • concurrent administration with itraconazole, clarithromycin, saquinavir plus ritonavir, darunavir plus ritonavir, or fosamprenavir alone or in combination with ritonavir, elbasvir plus grazoprevir, letermovir:
    • 20 mg once daily
fluvastatin (generics, Lescol® XL, generics) 20 mg, 40 mg capsules; 80 mg extended-release tablets
  • 80 mg once daily, as single dose or two divided doses
  • concurrent administration with cyclosporine, fluconazole:
    • do not exceed 20 mg twice daily
lovastatin (generics) 10 mg, 20 mg, 40 mg tablets
  • 80 mg once daily with evening meal 
  • concurrent administration with amiodarone: 
    • 40 mg once daily with evening meal 
  • concurrent administration with danazol, diltiazem, or verapamil: 
    • 20 mg once daily with evening meal
lovastatin (Altoprev®) 20 mg, 40 mg, 60 mg extended-release tablets
  • 60 mg once daily at bedtime
  • concurrent administration with amiodarone:
    • 40 mg once daily at bedtime
  • concurrent administration with danazol, diltiazem, or verapamil:
    • 20 mg once daily at bedtime
pitavastatin calcium (Livalo®) 1 mg, 2 mg, 4 mg tablets
  • 4 mg once daily
  • concurrent administration with rifampin:
    • 2 mg once daily
  • concurrent administration with erythromycin:
    • 1 mg once daily
pitavastatin magnesium (Zypitamag®) 1 mg, 2 mg, 4 mg tablets
  • 4 mg once daily
  • concurrent administration with rifampin:
    • 2 mg once daily
  • concurrent administration with erythromycin:
    • 1 mg once daily
pravastatin (Pravachol®, generics) 10 mg, 20 mg 40 mg, 80 mg tablets
  • 80 mg once daily
  • concurrent administration with immunosuppressives (e.g., cyclosporine):  
    • 20 mg once daily
  • concurrent administration with clarithromycin:
    • 40 mg once daily
rosuvastatin (Crestor®, generics) 5 mg, 10 mg, 20 mg, 40 mg tablets
  • 40 mg once daily
  • concurrent administration with gemfibrozil, lopinavir/ritonavir, or atazanavir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir::
    • 10 mg once daily
  • concurrent administration with cyclosporine or darolutamide:
    • 5 mg once daily
rosuvastatin (Ezallor Sprinkle®) 5 mg, 10 mg, 20 mg, 40 mg sprinkle capsules
  • 40 mg once daily
  • concurrent administration with gemfibrozil, lopinavir/ritonavir, atazanavir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir:
    • 10 mg once daily
  • concurrent administration with cyclosporine or darolutamide:
    • 5 mg once daily
simvastatin (Zocor®, FloLipid®, tablet generics) 5 mg, 10 mg, 20 mg, 40 mg, 80 mg tablets; 20 mg/5 mL, 40 mg/5 mL suspension
  • 40 mg once daily in evening for most patients*
  • concurrent administration with amiodarone, amlodipine, or ranolazine:
    • 20 mg once daily in evening
  • concurrent administration with verapamil, diltiazem, or dronedarone:
    • 10 mg once daily in evening
  • concurrent lomitapide: simvastatin dose should be reduced by 50%; simvastatin dose should not exceed 20 mg/day for most patients prescribed lomitapide concurrently (40 mg/day in patients on 80 mg/day dose for at least 1 year)
    • *80 mg dose restricted to those patients chronically maintained on 80 mg without evidence of myopathy
Table 2. HMG-CoA Reductase Inhibitor Combination Therapy – Maximum Recommended Adult Dosages1,2,15-17
Drug Dosage Form/Strength Maximum Recommended Dosage
amlodipine/atorvastatin (Caduet®, generics) 2.5 mg/10 mg, 2.5 mg/20 mg, 2.5 mg/40 mg, 5 mg/10 mg, 5 mg/20 mg, 5 mg/40 mg, 5 mg/80 mg, 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg, 10 mg/80 mg tablets
  • 10 mg/80 mg once daily
  • concurrent administration with nelfinavir:
    • 10 mg/40 mg once daily
  • concurrent administration with itraconazole, clarithromycin, saquinavir plus ritonavir, darunavir plus ritonavir, or fosamprenavir alone or in combination with ritonavir, elbasvir plus grazoprevir, letermovir:
    • 10 mg/20 mg once daily
ezetimibe/ rosuvastatin (Roszet®) 10 mg/5 mg, 10 mg/ 10mg, 10 mg/20 mg, 10 mg/40 mg oral tablets
  • 10 mg/40 mg once daily
  • concurrent administration with darolutamide:
    • 10 mg/ 5mg once daily
  • Concurrent administration with regorafenib:
    • 10 mg/10 mg once daily
  • Concurrent administration with sofosbuvir/velpatasvir/voxilaprevir and ledipasvir/sofosbuvir:
    • Avoid use
  • Concurrent administration with elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, atazanavir/ritonavir, and lopinavir/ritonavir:
    • 10 mg/10 mg once daily
ezetimibe/ simvastatin (Vytorin®, generics) 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg, 10 mg/80 mg tablets
  • 10 mg/40 mg once daily in evening for most patients*
  • concurrent administration with amiodarone, amlodipine, or ranolazine:
    • 10 mg /20 mg once daily in evening
  • concurrent administration with verapamil, diltiazem, or dronedarone:
    • 10 mg/10 mg once daily in evening
  • concurrent lomitapide: simvastatin dose should be reduced by 50%; simvastatin dose should not exceed 10 mg/20 mg daily for most patients prescribed lomitapide concurrently (10 mg/40 mg daily in patients on 80 mg/day dose for at least 1 year)
    • *10 mg/80 mg dose restricted to those patients chronically maintained on 80 mg without evidence of myopathy