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

1.2. Pediatrics

HMG-CoA reductase inhibitors are FDA-approved for use as a dietary adjunct to reduce total cholesterol, LDL-C, TG, and Apo B in adolescent boys, and girls who are at least one-year post-menarche, (for pravastatin, children and adolescents 8-18 years of age regardless of menarchal status) with elevated LDL-C due to heterozygous familial hypercholesterolemia. Pitavastatin calcium (Livalo®) is FDA-approved for use in children/adolescents over 8 years of age as an adjunct to diet to manage heterozygous familial hypercholesterolemia by lowering total cholesterol, LDL-C, and apo B1,2,13. Rosuvastatin has expanded FDA approval for use in children as young as 8 years of age with heterozygous familial hypercholesterolemia, and has gained FDA approval for homozygous familial hypercholesterolemia in pediatric patients 7-17 years of age.1,2,10 Simvastatin oral suspension (FloLipid®) has been approved for use in conjunction with diet to improve total cholesterol, LDL-C, and ApoB in pediatric patients 10-17 years (females at least one year post-menarche) with heterozygous familial hypercholesterolemia1,2,12. Safety and efficacy of pitavastatin magnesium (Zypitamag®) or rosuvastatin sprinkle capsules (Ezallor Sprinkle™) in pediatric patients have not been established1,2,13,14 . Safety and effectiveness of HMG-CoA reductase inhibitors in pre-menarchal girls or children younger than 10 years of age (for pravastatin and rosuvastatin in heterozygous familial hypercholesterolemia, younger than 8 years of age regardless of menarchal status; for rosuvastatin in homozygous familial hypercholesterolemia, younger than 7 years of age) have not been well established1,2,9,10.

Ezetemibe/simivastatin (Vytorin®) combination therapy has been effectively used to manage children and adolescents with heterozygous familial hypercholesterolemia 1,2,15. The amlodipine/atorvastatin (Caduet®) combination has not been FDA-approved for the pediatric population as safety and efficacy have not been established with this combination therapy1,2,16. The safety and efficacy of ezetimibe/ rosuvastatin (Roszet®) in children has not been established, and it is currently not FDA-approved in the pediatric population 1,2,17.

Maximum recommended doses for HMG-CoA reductase inhibitors as both monotherapy and combination therapy in pediatric patients are summarized in Tables 3 and 4.

Table 3. Maximum Recommended HMG-CoA Reductase Inhibitor Pediatric Dosages: Monotherapy1-6, 8-12
Treatment Indication Drug Name Maximum Recommended Dosage
Heterozygous familial hypercholesterolemia atorvastatin 10-17 years of age:  
20 mg once daily
Heterozygous familial hypercholesterolemia fluvastatin 10-17 years of age:  
80 mg daily, as single evening dose or two divided doses
Heterozygous familial hypercholesterolemia lovastatin (immediate-release only) 10-17 years of age:  
40 mg once daily with evening meal
Heterozygous familial hypercholesterolemia pitavastatin Greater than 8 years to 17 years of age:
4 mg once daily
Heterozygous familial hypercholesterolemia pitavastatin Greater than 8 years to 17 years of age:
4 mg once daily
Heterozygous familial hypercholesterolemia pravastatin

8-13 years of age:  
20 mg once daily

14-17 years of age:  
40 mg once daily
Heterozygous familial hypercholesterolemia rosuvastatin (tablets only)

8-9 years of age:
10 mg once daily

10-17 years of age:
20 mg once daily
Homozygous familial hypercholesterolemia rosuvastatin (tablets only) 7-17 years of age:
20 mg once daily
Heterozygous familial hypercholesterolemia simvastatin 10-17 years of age:
40 mg once daily in evening
Table 4. Maximum Recommended HMG-CoA Reductase Inhibitor Pediatric Dosages: Combination Therapy1,2,15
Treatment Indication Drug Name Maximum Recommended Dosage
Heterozygous familial hypercholesterolemia ezetimibe/simvastatin 10-17 years of age (females postmenarchal):
10 mg/40 mg once daily