The recommended starting dose is 100 mg/40 mg per day. For patients already taking simvastatin (10, 20, or 40 mg daily) with or without sitagliptin 100 mg daily, JUVISYNC may be initiated at the dose of 100 mg sitagliptin and the dose of simvastatin already being taken.

After initiation or titration of JUVISYNC, lipid levels may be analyzed after 4 or more weeks and dosage adjusted, if needed.

2.2 Patients with Renal Impairment
JUVISYNC is not recommended in patients with severe renal impairment or ESRD. JUVISYNC can be used in patients with normal renal function or mild renal impairment (creatinine clearance [CrCl] greater than or equal to 50 mL/min, approximately corresponding to serum creatinine levels of less than or equal to 1.7 mg/dL in men and less than or equal to 1.5 mg/dL in women), without adjustment of the sitagliptin dose. Because simvastatin does not undergo significant renal excretion, modification of the dose of the simvastatin component should not be necessary in patients with mild renal impairment.

For patients with moderate renal impairment (CrCl greater than or equal to 30 to less than 50 mL/min, approximately corresponding to serum creatinine levels of greater than 1.7 to less than or equal to 3.0 mg/dL in men and greater than 1.5 to less than or equal to 2.5 mg/dL in women), the recommended starting dose of JUVISYNC is 50 mg/40 mg once daily. For patients with moderate renal impairment who are already taking simvastatin (10, 20, or 40 mg daily) with or without sitagliptin 50 mg daily, JUVISYNC may be initiated at the dose of 50 mg sitagliptin and the dose of simvastatin already being taken.

Assessment of renal function is recommended prior to initiation of JUVISYNC and periodically thereafter. Creatinine clearance can be estimated from serum creatinine using the Cockcroft-Gault formula. [See Warnings and Precautions (5.4); Clinical Pharmacology (12.3).] There have been postmarketing reports of worsening renal function in patients with renal impairment treated with sitagliptin, some of whom were prescribed inappropriate doses of sitagliptin.

2.3 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
When JUVISYNC is used in combination with an insulin secretagogue (e.g., sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia. [See Warnings and Precautions (5.5).]

2.4 Coadministration with Other Drugs

Patients taking Verapamil, Diltiazem, or Dronedarone

•The dose of simvastatin should not exceed 10 mg per day (100 mg/10 mg or 50 mg/10 mg per day of JUVISYNC) [see Warnings and Precautions (5.2); Drug Interactions (7.3); Clinical Pharmacology (12.3)].

Patients taking Amiodarone, Amlodipine or Ranolazine

•The dose of simvastatin should not exceed 20 mg per day (100 mg/20 mg or 50 mg/20 mg per day of JUVISYNC) [see Warnings and Precautions (5.2); Drug Interactions (7.3); Clinical Pharmacology (12.3)].

2.5 Patients with Homozygous Familial Hypercholesterolemia
The recommended dosage is 100 mg/40 mg (for patients with normal or mildly impaired renal function) or 50 mg/40 mg (for patients with moderately impaired renal function) per day in the evening. JUVISYNC should be used as an adjunct to other lipid-lowering treat