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 with elevated LDL-C due to heterozygous familial hypercholesterolemia. Pravastatin is approved for children and adolescents 8-18 years of age regardless of menarchal status. 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 B^1-7. 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^1,9. Simvastatin oral suspension (FloLipid) and tablets are approved for use in conjunction with diet to improve total cholesterol, LDL-C, and ApoB in pediatric patients 10-17 years of age (females at least one year post-menarche) with heterozygous familial hypercholesterolemia.1,11 Safety and efficacy of pitavastatin magnesium (Zypitamag) in pediatric patients have not been established^1,12. 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 established^1,8,9.

Ezetemibe/simivastatin (Vytorin) combination therapy has been effectively used to manage children and adolescents with heterozygous familial hypercholesterolemia^1,14. 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 therapy^1,15. 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^1,16.

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: Monotherapy^{1-5, 7-11, 13}

Drug Name	Treatment Indication	Maximum Recommended Dosage
atorvastatin	Heterozygous familial hypercholesterolemia	10-17 years of age:   20 mg once daily
fluvastatin	Heterozygous familial hypercholesterolemia	10-16  years of age:   80 mg daily, as single evening dose or two divided doses
lovastatin (immediate-release only)	Heterozygous familial hypercholesterolemia	10-17 years of age:   40 mg once daily with evening meal
pitavastatin	Heterozygous familial hypercholesterolemia	Greater than 8 years to 17 years of age: 4 mg once daily
pitavastatin	Heterozygous familial hypercholesterolemia	Greater than 8 years to 17 years of age: 4 mg once daily
pravastatin	Heterozygous familial hypercholesterolemia	8-13 years of age:   20 mg once daily 14-18  years of age:   40 mg once daily
rosuvastatin (tablets only)	Heterozygous familial hypercholesterolemia	8-9 years of age: 10 mg once daily 10-17 years of age: 20 mg once daily
rosuvastatin (tablets only)	Homozygous familial hypercholesterolemia	7-17 years of age: 20 mg once daily
simvastatin	Heterozygous familial hypercholesterolemia	10-17 years of age: 40 mg once daily in evening

Table 4. Maximum Recommended HMG-CoA Reductase Inhibitor Pediatric Dosages: Combination Therapy^1,14

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