1 INDICATIONS AND USAGE
JUVISYNC™ (sitagliptin and simvastatin) is indicated in patients for whom treatment with both sitagliptin and simvastatin is appropriate.

1.1 Sitagliptin
Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. [See Clinical Studies (14.1).]

1.2 Simvastatin
Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. In patients with coronary heart disease (CHD) or at high risk of CHD, simvastatin can be started simultaneously with diet.

Reductions in Risk of CHD Mortality and Cardiovascular Events

In patients at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, simvastatin is indicated to:

•Reduce the risk of total mortality by reducing CHD deaths.
•Reduce the risk of non-fatal myocardial infarction and stroke.
•Reduce the need for coronary and non-coronary revascularization procedures.

Hyperlipidemia

Simvastatin is indicated to:

•Reduce elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hyperlipidemia (Fredrickson type IIa, heterozygous familial and nonfamilial) or mixed dyslipidemia (Fredrickson type IIb).
•Reduce elevated TG in patients with hypertriglyceridemia (Fredrickson type lV hyperlipidemia).
•Reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia (Fredrickson type lll hyperlipidemia).
•Reduce total-C and LDL-C in patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

1.3 Important Limitations of Use
JUVISYNC should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings.

JUVISYNC has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using JUVISYNC. [See Warnings and Precautions (5.1).]

JUVISYNC has not been studied in conditions where the major abnormality is elevation of chylomicrons (i.e., hyperlipidemia Fredrickson types I and V).

Because doses of JUVISYNC appropriate for patients with severe renal impairment (CrCl <30 mL/min, approximately corresponding to serum creatinine levels of >3.0 mg/dL in men and >2.5 mg/dL in women) or end-stage renal disease (ESRD) are not available in this combination product, JUVISYNC is not recommended in patients with severe renal impairment or ESRD.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosing
The dosages for therapy with JUVISYNC are 100 mg/10 mg, 100 mg/20 mg, 100 mg/40 mg, 50 mg/10 mg, 50 mg/20 mg, and 50 mg/40 mg (si