vastatin combinations have not been established in neonates, infants, children < 10 years, or in pre-pubertal females. Counsel adolescent females regarding appropriate methods of contraception while on therapy. The long-term efficacy of therapy in childhood to reduce morbidity and mortality later in adulthood has not been established. Because cholesterol plays a crucial role in growth and development, the clinical implications of using pharmacologic therapy to alter the normal production of cholesterol in young children in not clear. Because of these potential safety concerns and lack of safety data, most experts generally recommend delaying cholesterol-lowering medications until the child is at least 8—10 years old. In some cases of severe familial hypercholesterolemia, however, HMG-CoA reductase inhibitors have been used in younger children with careful monitoring of growth and development.
Asian patients
The manufacturer recommends that Chinese patients taking lipid-modifying doses of niacin-containing products (>= 1 g/day niacin) should not receive the 10/80 mg dose of ezetimibe;simvastatin due to increased risk for myopathy and caution should be used when treating these patients with doses of simvastatin higher than 20 mg/day. In a double-blind, randomized cardiovascular outcomes trial, there was an increased incidence of myopathy in Chinese patients compared with non-Chinese patients taking ezetimibe; simvastatin 10/40 mg coadministered with lipid-modifying doses of niacin-containing products. Because the risk of myopathy is dose-related with simvastatin, the dose should be limited this population. It is unknown if this increased risk of myopathy observed in Chinese patients applies to other Asian patients.
Diabetes mellitus
If ezetimibe; simvastatin is initiated in a patient with diabetes, increased monitoring of blood glucose may be warranted. Increased hemoglobin A1c, hyperglycemia, and worsening glycemic control have been reported during therapy with HMG-CoA reductase inhibitors. Because the use of statins has been associated with significant benefit for cardiovascular risk reduction and all-cause mortality at comparable rates in diabetic and non-diabetic patients , no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes mellitus should be considered when initiating simvastatin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established. Although an analysis of participants from the JUPITER trial found an increased incidence of developing diabetes in patients allocated to rosuvastatin compared to placebo (270 reports of diabetes vs. 216 in the placebo group; HR 1.25, 95% CI 1.05—1.49, p = 0.01), the cardiovascular and mortality benefits of statin therapy exceeded the diabetes hazard even in patients at high risk for developing diabetes (i.e., patients with one or more major diabetes risk factor: metabolic syndrome, impaired fasting glucose, BMI >= 30 kg/m2, or HbA1c > 6%). In patients at high risk for developing diabetes, treatment with rosuvastatin was associated with a 39% reduction in the primary endpoint (composite of non-fatal myocardial infarction, non-fatal stroke, unstable angina or revascularization, and cardiovascular death) (HR 0.61, 95% CI 0.47—0.79, p = 0.0001),nonsignificant reductions in venous thromb |
