le-blind, placebo-controlled study, 175 patients (99 adolescent boys and 76 post-menarchal girls) 10-17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (HeFH) were randomized to simvastatin (n=106) or placebo (n=67) for 24 weeks (base study). Inclusion in the study required a baseline LDL-C level between 160 and 400 mg/dL and at least one parent with an LDL-C level >189 mg/dL. The dosage of simvastatin (once daily in the evening) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter. In a 24-week extension, 144 patients elected to continue therapy with simvastatin 40 mg or placebo.
ZOCOR significantly decreased plasma levels of total-C, LDL-C, and Apo B (see Table 8). Results from the extension at 48 weeks were comparable to those observed in the base study.
Table 8: Lipid-Lowering Effects of Simvastatin in Adolescent Patients with Heterozygous Familial Hypercholesterolemia (Mean Percent Change from Baseline) Dosage
Duration
N
Total-C
LDL-C
HDL-C
TG*
Apo B
* median percent change
Placebo
24 Weeks
67
% Change from Baseline
(95% CI) 1.6
(-2.2, 5.3) 1.1
(-3.4, 5.5) 3.6
(-0.7, 8.0) -3.2
(-11.8, 5.4) -0.5
(-4.7, 3.6)
Mean baseline, mg/dL
(SD)
278.6
(51.8)
211.9
(49.0)
46.9
(11.9)
90.0
(50.7)
186.3
(38.1)
ZOCOR 24 Weeks 106 % Change from Baseline
(95% CI)
-26.5
(-29.6, -23.3)
-36.8
(-40.5, -33.0)
8.3
(4.6, 11.9)
-7.9
(-15.8, 0.0)
-32.4
(-35.9, -29.0)
Mean baseline, mg/dL
(SD)
270.2
(44.0)
203.8
(41.5)
47.7
(9.0)
78.3
(46.0)
179.9
(33.8)
After 24 weeks of treatment, the mean achieved LDL-C value was 124.9 mg/dL (range: 64.0-289.0 mg/dL) in the ZOCOR 40 mg group compared to 207.8 mg/dL (range: 128.0-334.0 mg/dL) in the placebo group.
The safety and efficacy of doses above 40 mg daily have not been studied in children with HeFH. The long-term efficacy of simvastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
16 HOW SUPPLIED/STORAGE AND HANDLING
No. 8360 — Tablets ZOCOR 5 mg are buff, oval, film-coated tablets, coded MSD 726 on one side and ZOCOR 5 on the other. They are supplied as follows:
NDC 0006-0726-31 unit of use bottles of 30.
No. 8146 — Tablets ZOCOR 10 mg are peach, oval, film-coated tablets, coded MSD 735 on one side and plain on the other. They are supplied as follows:
NDC 0006-0735-31 unit of use bottles of 30
NDC 0006-0735-54 unit of use bottles of 90.
No. 8147 — Tablets ZOCOR 20 mg are tan, oval, film-coated tablets, coded MSD 740 on one side and plain on the other. They are supplied as follows:
NDC 0006-0740-31 unit of use bottles of 30
NDC 0006-0740-54 unit of use bottles of 90.
No. 8148 — Tablets ZOCOR 40 mg are brick red, oval, film-coated tablets, coded MSD 749 on one side and plain on the other. They are supplied as follows:
NDC 0006-0749-31 unit of use bottles of 30
NDC 0006-0749-54 unit of use bottles of 90.
No. 6577 — Tablets ZOCOR 80 mg are brick red, capsule-shaped, film-coated tablets, coded 543 on one side and 80 on the other. They are supplied as follows:
NDC 0006-0543-
