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Hypertriglyceridemia (Fredrickson type lV)

The results of a subgroup analysis in 74 patients with type lV hyperlipidemia from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 6.

Dysbetalipoproteinemia (Fredrickson type lll)

The results of a subgroup analysis in 7 patients with type lll hyperlipidemia (dysbetalipoproteinemia) (apo E2/2) (VLDL-C/TG>0.25) from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 7.

Homozygous Familial Hypercholesterolemia

In a controlled clinical study, 12 patients 15-39 years of age with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses, or 80 mg/day in 3 divided doses. In 11 patients with reductions in LDL-C, the mean LDL-C changes for the 40 and 80 mg doses were 14% (range 8% to 23%, median 12%) and 30% (range 14% to 46%, median 29%), respectively. One patient had an increase of 15% in LDL-C. Another patient with absent LDL-C receptor function had an LDL-C reduction of 41% with the 80 mg dose.

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 4,444 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.

14.2 Clinical Studies in Adolescents

In a double-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.

Simvastatin 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.

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 simvastatin 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

Simvastatin Tablets USP, 80 mg are brown colored, oval shaped, biconvex, film-coated tablets, debossed ‘RDY’ on one side and ’268′ on other side. They are supplied as follows:

Bottles of 30 NDC 68645-263-54

Storage

WARNING: KEEP OUT OF THE REACH OF CHILDREN

Tamper Evident: Do Not Use this product if bottle seal is not intact

CHILD-RESISTANT: Tighten cap on bottle after use.

Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature].

Protect from moisture, freezing and excessive heat.
Dispsense contents in a light-resistant container.

17 PATIENT COUNSELING INFORMATION

Patients should be advised to adhere to their National Cholesterol Education Program (NCEP)-recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel.

Patients should be advised about substances they should not take concomitantly with simvastatin [see Warnings and Precautions (5.1)]. Patients should also be advised to inform other healthcare professionals prescribing a new medication that they are taking simvastatin.

17.1 Muscle Pain

All patients starting therapy with simvastatin should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. The risk of this occurring is increased when taking certain types of medication or consuming larger quantities of grapefruit juice. They should discuss all medication, both prescription and over the counter, with their healthcare professional.

17.2 Liver Enzymes

It is recommended that liver function tests be performed before the initiation of simvastatin, and thereafter when clinically indicated. Patients titrated to the 80 mg dose should receive an additional test prior to titration, 3 months after titration to the 80 mg dose, and periodically thereafter (e.g., semiannually) for the first year of treatment.

17.3 Pregnancy

Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using simvastatin. Discuss future pregnancy plans with your patients, and discuss when to stop taking simvastatin if they are trying to conceive. Patients should be advised that if they become pregnant they should stop taking simvastatin and call their healthcare professional.

17.4 Breastfeeding

Women who are breastfeeding should not use simvastatin. Patients who have a lipid disorder and are breastfeeding should be advised to discuss the options with their healthcare professional.

Rx Only

Manufactured by:
Dr. Reddy’s Laboratories Limited
Bachepalli – 502 325 INDIA

Distributed by:
The Kroger Co.
1014 Vine Street
Cincinnati, OH 45202

Packaged by:
Legacy Pharmaceutical Packaging LLC Earth City, MO 63045

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION

(click image for full-size original)

Kroger Simivastatin 80mg Bottle Label

Revised: 01/2012 Legacy Pharmaceutical Packaging