Simvastatin / Sitagliptin Dosage

Applies to the following strengths: 10 mg-50 mg; 20 mg-50 mg; 40 mg-50 mg; 10 mg-100 mg; 20 mg-100 mg; 40 mg-100 mg

Usual Adult Dose for:

Diabetes Type 2
Hyperlipidemia
Homozygous Familial Hypercholesterolemia
Heterozygous Familial Hypercholesterolemia
Cardiovascular Risk Reduction

Usual Adult Dose for Diabetes Type 2

Initial dose: Simvastatin 40 mg-sitagliptin 100 mg orally once a day in the evening
Maintenance dose: Simvastatin 10 to 50 mg-sitagliptin 50 to 100 mg orally once a day in the evening

For patients already taking simvastatin with or without sitagliptin: Initiate at the dose of simvastatin already being taken and sitagliptin at 100 mg orally daily.

For patients taking verapamil, diltiazem, or dronedarone: Simvastatin 10 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 10 mg per day.

For patients taking amiodarone, amlodipine or ranolazine: Simvastatin 20 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 20 mg per day.

Patients with Homozygous Familial Hypercholesterolemia: Simvastatin 40 mg-sitagliptin 100 mg orally daily.

Concomitant use with lomitapide: Simvastatin 20 mg-sitagliptin 100 mg orally daily.

Chinese patients taking Lipid-Modifying doses (greater than or equal to 1 g per day of Niacin): Simvastatin 40 mg-sitagliptin 50 to 100 mg should be used with caution.

Comments: If this drug is used in combination with an insulin secretagogue or with insulin, a lower dose of insulin or insulin secretagogue may be required to reduce risk of hypoglycemia.

Uses: Simvastatin: Reduce risk of non-fatal myocardial infarction, stroke, and the need for revascularization in patients at high risk of coronary events. Reduce elevated total cholesterol, LDL, TG, VLDL and increase HDL in patients with primary hyperlipidemia (Heterozygous Familial and Nonfamilial) and mixed dyslipidemia. Reduce elevated TG in patients with hypertriglyceridemia and reduce TG and VLDL-C in patients with primary dysbetalipoproteinemia. Reduce total cholesterol in patients with homozygous familial hypercholesterolemia. Sitagliptin: Adjunct therapy to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Usual Adult Dose for Hyperlipidemia

Initial dose: Simvastatin 40 mg-sitagliptin 100 mg orally once a day in the evening
Maintenance dose: Simvastatin 10 to 50 mg-sitagliptin 50 to 100 mg orally once a day in the evening

For patients already taking simvastatin with or without sitagliptin: Initiate at the dose of simvastatin already being taken and sitagliptin at 100 mg orally daily.

For patients taking verapamil, diltiazem, or dronedarone: Simvastatin 10 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 10 mg per day.

For patients taking amiodarone, amlodipine or ranolazine: Simvastatin 20 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 20 mg per day.

Patients with Homozygous Familial Hypercholesterolemia: Simvastatin 40 mg-sitagliptin 100 mg orally daily.

Concomitant use with lomitapide: Simvastatin 20 mg-sitagliptin 100 mg orally daily.

Chinese patients taking Lipid-Modifying doses (greater than or equal to 1 g per day of Niacin): Simvastatin 40 mg-sitagliptin 50 to 100 mg should be used with caution.

Usual Adult Dose for Homozygous Familial Hypercholesterolemia

Initial dose: Simvastatin 40 mg-sitagliptin 100 mg orally once a day in the evening
Maintenance dose: Simvastatin 10 to 50 mg-sitagliptin 50 to 100 mg orally once a day in the evening

For patients already taking simvastatin with or without sitagliptin: Initiate at the dose of simvastatin already being taken and sitagliptin at 100 mg orally daily.

For patients taking verapamil, diltiazem, or dronedarone: Simvastatin 10 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 10 mg per day.

For patients taking amiodarone, amlodipine or ranolazine: Simvastatin 20 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 20 mg per day.

Patients with Homozygous Familial Hypercholesterolemia: Simvastatin 40 mg-sitagliptin 100 mg orally daily.

Concomitant use with lomitapide: Simvastatin 20 mg-sitagliptin 100 mg orally daily.

Chinese patients taking Lipid-Modifying doses (greater than or equal to 1 g per day of Niacin): Simvastatin 40 mg-sitagliptin 50 to 100 mg should be used with caution.

Usual Adult Dose for Heterozygous Familial Hypercholesterolemia

Initial dose: Simvastatin 40 mg-sitagliptin 100 mg orally once a day in the evening
Maintenance dose: Simvastatin 10 to 50 mg-sitagliptin 50 to 100 mg orally once a day in the evening

For patients already taking simvastatin with or without sitagliptin: Initiate at the dose of simvastatin already being taken and sitagliptin at 100 mg orally daily.

For patients taking verapamil, diltiazem, or dronedarone: Simvastatin 10 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 10 mg per day.

For patients taking amiodarone, amlodipine or ranolazine: Simvastatin 20 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 20 mg per day.

Patients with Homozygous Familial Hypercholesterolemia: Simvastatin 40 mg-sitagliptin 100 mg orally daily.

Concomitant use with lomitapide: Simvastatin 20 mg-sitagliptin 100 mg orally daily.

Chinese patients taking Lipid-Modifying doses (greater than or equal to 1 g per day of Niacin): Simvastatin 40 mg-sitagliptin 50 to 100 mg should be used with caution.

Usual Adult Dose for Cardiovascular Risk Reduction

Initial dose: Simvastatin 40 mg-sitagliptin 100 mg orally once a day in the evening
Maintenance dose: Simvastatin 10 to 50 mg-sitagliptin 50 to 100 mg orally once a day in the evening

For patients already taking simvastatin with or without sitagliptin: Initiate at the dose of simvastatin already being taken and sitagliptin at 100 mg orally daily.

For patients taking verapamil, diltiazem, or dronedarone: Simvastatin 10 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 10 mg per day.

For patients taking amiodarone, amlodipine or ranolazine: Simvastatin 20 mg-sitagliptin 50 or 100 mg orally daily. Dose of simvastatin should not exceed 20 mg per day.

Patients with Homozygous Familial Hypercholesterolemia: Simvastatin 40 mg-sitagliptin 100 mg orally daily.

Concomitant use with lomitapide: Simvastatin 20 mg-sitagliptin 100 mg orally daily.

Chinese patients taking Lipid-Modifying doses (greater than or equal to 1 g per day of Niacin): Simvastatin 40 mg-sitagliptin 50 to 100 mg should be used with caution.

Renal Dose Adjustments

Severe renal dysfunction (CrCl less than 30 mL/min): Appropriate doses are not available and therefore use is not recommended
Moderate renal dysfunction (CrCl 30 to less than 50 mL/min): Initial dose: simvastatin 40 mg-sitagliptin 50 mg orally once a day; for patients already taking simvastatin with or without sitagliptin 50 mg daily, the initial dose should be the dose of simvastatin already being taken and sitagliptin 50 mg.
Mild renal dysfunction (CrCl greater than 50 mL/min): No adjustment recommended.

Patients with Homozygous Familial Hypercholesterolemia:

Severe renal dysfunction (CrCl less than 30 mL/min): Appropriate doses are not available and therefore use is not recommended
Moderate renal dysfunction (CrCl 30 to less than 50 mL/min): Simvastatin 40 mg-sitagliptin 50 mg orally once a day in the evening.
Mild renal dysfunction (CrCl greater than 50 mL/min): Simvastatin 40 mg-sitagliptin 100 mg orally daily.

Comments: Simvastatin-sitagliptin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Concomitant use with lomitapide:

Severe renal dysfunction (CrCl less than 30 mL/min): Not recommended
Moderate renal dysfunction (CrCl 30 to less than 50 mL/min): Maximum dose should not exceed simvastatin 20 mg-sitagliptin 50 mg orally daily. If a patient had previously taken simvastatin 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity, the maximum dose should not exceed simvastatin 40 mg-sitagliptin 50 orally daily.
Mild renal dysfunction (CrCl greater than 50 mL/min): Maximum dose should not exceed simvastatin 20 mg-sitagliptin 100 mg orally daily. If a patient had previously taken simvastatin 80 mg daily chronically (e.g., for 12 months or more) without evidence of muscle toxicity, the maximum dose should not exceed simvastatin 40 mg-sitagliptin 100 orally daily.

Liver Dose Adjustments

Contraindicated

Dose Adjustments

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

Precautions

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

Tablets must never be split before swallowing.
Tablets can be taken with or without food, although co-administration with high-fat meals is not recommended.

Monitoring:

Metabolic: Blood glucose (A1C) levels
Hepatic: Transaminases and cholesterol levels

Patient advice:

Diet, a regular exercise program and periodic testing of fasting lipid panel is recommended.
Inform other healthcare professionals prescribing a new medication or increasing the dose of existing medication that you are taking simvastatin-sitagliptin.
Measurement of A1C is especially useful for evaluating long-term glycemic control.
There is a potential need to adjust the dose or discontinue this drug based on changes of renal function over time.
Report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice, unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if these muscle signs persist after discontinuing simvastatin-sitagliptin.
Instruct patients to contact their health care provider if they develop severe and persistent joint pain