What is the role of statins in the treatment of pediatric lipid disorders?

Updated: Jun 27, 2019
  • Author: Henry J Rohrs, III, MD; Chief Editor: Stuart Berger, MD  more...
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Answer

Statin use has markedly increased in children because these drugs are well tolerated, safe, and efficacious and are now considered first-line therapy. [21] They are approved for use in children as young as age 10 years, and pravastatin is approved for children as young as age 8 years.

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonate. This is the rate-limiting step in the synthesis of cholesterol. Inhibition of HMG-CoA reductase blocks hepatocyte synthesis of cholesterol. This stimulates the hepatocyte to produce more LDL-Rs. In turn, LDL-R expression on the surface of hepatocytes is increased, which increases LDL clearance from the circulation.

Currently available statins and their doses are shown in Table 5, below. In children, the lowest available dosage form should be used as the starting dose. Dosage increases should be considered every 6-12 weeks until the LDL-C level is less than 130 mg/dL (ideally less than 110 mg/dL) or until the maximum tolerable dose is reached.

After the LDL-C level declines to less than 130 mg/dL, the dose does not need to be further increased.

Table 5. Dosing of HMG-CoA–Reductase Inhibitors (Open Table in a new window)

Generic Name

Adult Dose

Pediatric Dose

Dose Adjustment for Renal Insufficiency or Coadministration with Food or Drugs That Decrease Clearance*

Lovastatin (Mevacor)

Initial: 20 mg/d orally every bedtime

Followed by: 10-80 mg/d orally every bedtime or divided twice daily

10-17 years: 10-20 mg/d orally every bedtime initially; maintenance dosage ranges from 10-40 mg/d

Not to exceed 20 mg/d

Simvastatin (Zocor)

Initial: 5-10 mg/d orally every bedtime

Followed by 5-80 mg/d orally every bedtime or divided twice daily

10-17 years: 10 mg/d orally every bedtime initially; maintenance dosage ranges from 10-40 mg/d

5 mg/d initially; not to exceed 20 mg/d

Pravastatin (Pravachol)

Initial: 10-20 mg/d orally every bedtime

Followed by 5-40 mg/d orally every bedtime

8-13 years: 20 mg orally every day

14-18 years: 40 mg orally every day

Initiate at 5-10 mg/d; not to exceed 20 mg/d (also decrease with hepatic impairment)

Fluvastatin (Lescol)

Initial: 20-30 mg/d orally every bedtime

Followed by 20-80 mg/d orally every bedtime; for 80 mg/d, divide twice daily

10-16 years: 20 mg orally every day initially; maintenance dosage ranges from 20-80 mg/d

No adjustment

Atorvastatin (Lipitor)

Initial: 10 mg/d PO orally every bedtime

Followed by 10-80 mg/d orally every bedtime

10-17 years: 10 mg orally every day initially; maintenance dosages do not exceed 20 mg/d

No adjustment for renal insufficiency; decrease dose or avoid with drugs that decrease clearance

Pitavastatin (Livalo) [22]

Initial: 2 mg/d PO qd

May increase to 4 mg/d

8-17 years: 2 mg PO qd initially; may increase to 4 mg/d

Lower dose with renal impairment, coadministration with erythromycin or rifampin, contraindicated with cyclosporine or active liver disease

Rosuvastatin (Crestor)

10-20 mg orally every day initially; maintenance dosage range is 5-40 mg/d

Not established

5 mg orally every day initially; not to exceed 10 mg/d

* Renal insufficiency is indicated by a creatinine clearance of less than 30 mL/min; agents known to decrease HMG-CoA–reductase inhibitor clearance include grapefruit juice, gemfibrozil, ritonavir, cyclosporine, danazol, amiodarone, azole antifungals, macrolide antibiotics, and verapamil.

Statins have been associated with hepatocellular toxicity and rhabdomyolysis. Frank rhabdomyolysis is rare. The likelihood of rhabdomyolysis increases when a statin is used with cyclosporine, gemfibrozil, erythromycin, azole antifungal agents, niacin, or antiretroviral therapies. The risk also increases with higher doses.

Previously, close monitoring of liver function was recommended, but as of February 28, 2012 the United States Food and Drug Administration (FDA) revised labels for all statins to remove the need for routine periodic monitoring of liver enzymes. The labels now recommend aspartate aminotransferase (AST)/alanine aminotransferase (ALT) should be obtained before starting statin therapy and as clinically indicated thereafter. This change was recommended after the FDA concluded that serious liver injury with statins is rare and unpredictable in individuals and that routine monitoring of liver enzymes did not appear effective in detecting or preventing serious liver injury.

Studies have reported decreases in LDL-C levels of as much as 40% and increases in HDL-C levels of 23%. Increases in ALT, AST, and creatine kinase (CK) levels outside the reference range are reported in most studies to occur in 1-5% of cases. CK screening for myopathy is not recommended. There appears to be no data on the risk of diabetes development in children treated with statins.

Mendelson et al investigated the effectiveness of statins and the effect of baseline factors on low-density lipoprotein cholesterol (LDL-C) reduction in a study of 97 children over 3.5 years. The primary outcome was first achieving goal LDL-C, defined as < 130 mg/dL, or < 100 mg/dL with high-level risk factors. The cumulative probability of achieving goal LDL-C within 1 year was 60%; a lower probability of achieving LDL-C goals was associated with higher baseline LDL-C and male sex. [23]


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