Niacin/Simvastatin use in specific populations

# =Use In Specific Populations

## Pregnancy
Pregnancy Category X  
SIMCOR is contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Serum cholesterol and triglycerides increase during normal pregnancy. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy. There are no adequate and well-controlled studies of SIMCOR use during pregnancy; however, there are rare reports of congenital anomalies in infants exposed to HMG-CoA reductase inhibitors in utero. Animal reproduction studies of simvastatin in rats and rabbits showed no evidence of teratogenicity. SIMCOR may cause fetal harm when administered to a pregnant woman. If SIMCOR is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
SIMCOR contains simvastatin (a HMG-CoA reductase inhibitor) and Niacin (nicotinic acid). There are rare reports of congenital anomalies following intrauterine exposure to HMG-CoA reductase inhibitors. In a review of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or another structurally related HMG-CoA reductase inhibitor, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed those expected in the general population. However, the study was only able to exclude a 3- to 4-fold increased risk of congenital anomalies over the background rate. In 89% of these cases, drug treatment was initiated prior to pregnancy and was discontinued during the first trimester when pregnancy was identified. It is not known whether Niacin at doses used for lipid disorders can cause fetal harm when administered to a pregnant woman.
Simvastatin was not teratogenic in rats or rabbits at doses that resulted in 3 times the human exposure based on mg/m2 surface area. However, in studies with another structurally-related HMG-CoA reductase inhibitor, skeletal malformations were observed in rats and mice. Animal reproduction studies have not been conducted with niacin.
Women of childbearing potential, who require SIMCOR treatment for a lipid disorder, should use effective contraception. Patients trying to conceive should contact their prescriber to discuss stopping SIMCOR treatment. If pregnancy occurs, SIMCOR should be immediately discontinued.

## Nursing Mothers
It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Niacin is excreted into human milk but the actual infant dose or infant dose as a percent of the maternal dose is not known. Because of the potential for serious adverse reactions in nursing infants, nursing mothers who require SIMCOR treatment should not breastfeed their infants. A decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother .

## Pediatric Use
The safety and effectiveness of SIMCOR in pediatric patients have not been established.

## Geriatric Use
There were 281 (30.8%) patients aged 65 years and older treated with SIMCOR in Phase III clinical studies. No overall differences in safety and effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. A pharmacokinetic study with simvastatin showed the mean plasma level of HMG-CoA reductase inhibitory activity to be approximately 45% higher in elderly patients between 70-78 years of age compared with patients between 18-30 years of age.
Because advanced age (65 years) is a predisposing factor for myopathy, including rhabdomyolysis, SIMCOR should be prescribed with caution in the elderly. In a clinical trial of patients treated with simvastatin 80 mg/day, patients 65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age .

## Gender
Data from the clinical trials suggest that women have a greater hypolipidemic response than men at equivalent doses of Niacin extended-release. No consistent gender differences in efficacy and safety were observed in SIMCOR studies.

## Renal Impairment
No pharmacokinetic studies have been conducted in patients with renal impairment for SIMCOR. Caution should be exercised when SIMCOR is administered to patients with renal disease. For patients with severe renal insufficiency, SIMCOR should not be started unless the patient has already tolerated treatment with simvastatin at a dose of 10 mg or higher. Caution should be exercised when SIMCOR is administered to these patients and they should be closely monitored.

## Hepatic Impairment
No pharmacokinetic studies have been conducted in patients with hepatic insufficiency for SIMCOR .