trolled, 3-period crossover study are presented in Table 19.
Table 19 Six-week, Lipid-lowering Effects of Simvastatin in Type lll Hyperlipidemia Median Percent Change (min, max) from Baseline * TREATMENT N Total-C LDL-C + IDL HDL-C TG VLDL-C + IDL Non-HDL-C
*
The median baseline values (mg/dL) were: total-C = 324, LDL-C = 121, HDL-C = 31, TG = 411, VLDL-C = 170, and non-HDL-C = 291.
Placebo 7 -8
(-24, +34) -8
(-27, +23) -2
(-21, +16) +4
(-22, +90) -4
(-28, +78) -8
(-26, -39)
Simvastatin 40 mg/day 7 -50
(-66, -39) -50
(-60, -31) +7
(-8, +23) -41
(-74, -16) -58
(-90, -37) -57
(-72, -44)
Homozygous Familial Hypercholesterolemia
In a controlled clinical study, 4 patients, 19-27 years of age, with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses. Reductions in LDL-C were observed for all patients. The mean LDL-C reduction for the 40 mg dose was 14% (range 8% to 23%, median 12%).
Endocrine Function
In clinical studies, simvastatin did not impair adrenal reserve or significantly reduce basal plasma cortisol concentration. Small reductions from baseline in basal plasma testosterone in men were observed in clinical studies with simvastatin, an effect also observed with other statins and the bile acid sequestrant cholestyramine. There was no effect on plasma gonadotropin levels. In a placebo-controlled, 12-week study there was no significant effect of simvastatin 80 mg on the plasma testosterone response to human chorionic gonadotropin. In another 24-week study, simvastatin 20-40 mg had no detectable effect on spermatogenesis. In 4S, in which 4444 patients were randomized to simvastatin 20-40 mg/day or placebo for a median duration of 5.4 years, the incidence of male sexual adverse events in the two treatment groups was not significantly different. Because of these factors, the small changes in plasma testosterone are unlikely to be clinically significant. The effects, if any, on the pituitary-gonadal axis in pre-menopausal women are unknown.
16 HOW SUPPLIED/STORAGE AND HANDLING
JUVISYNC 100 mg/10 mg tablets are pink-beige, bi-convex round, film-coated tablets, coded with the Merck logo and "753" on one side and plain on the other. They are supplied as follows:
NDC 0006-0753-31 unit of use bottles of 30
NDC 0006-0753-54 unit of use bottles of 90
NDC 0006-0753-82 bottles of 1000.
JUVISYNC 100 mg/20 mg tablets are pink-beige, bi-convex modified capsule-shaped, film-coated tablets, coded with the Merck logo and "757" on one side and plain on the other. They are supplied as follows:
NDC 0006-0757-31 unit of use bottles of 30
NDC 0006-0757-54 unit of use bottles of 90
NDC 0006-0757-82 bottles of 1000.
JUVISYNC 100 mg/40 mg tablets are orange-beige, bi-convex modified capsule-shaped, film-coated tablets, coded with the Merck logo and "773" on one side and plain on the other. They are supplied as follows:
NDC 0006-0773-31 unit of use bottles of 30
NDC 0006-0773-54 unit of use bottles of 90
NDC 0006-0773-82 bottles of 1000.
Storage
Store at 20-25°C (68-77°F), excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature.] Store in a dry place with cap tightly closed.
Storage of 1000 count bottles
Dispense into a USP tightly closed, moisture-resistant container.
17 PATIENT COUNSELING INFORMATION
See FDA-approved Medication Guide.
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