Sitagliptin and simvastatin

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

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]

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.

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.

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 (HoFH) as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) or if such treatments are unavailable.

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]

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.

Sitagliptin

During controlled clinical trials in healthy subjects, single doses of up to 800 mg sitagliptin were administered. Maximal mean increases in QTc of 8.0 msec were observed in one study at a dose of 800 mg sitagliptin, a mean effect that is not considered clinically important [see CLINICAL PHARMACOLOGY]. There is no experience with doses above 800 mg in humans. In Phase I multiple-dose studies, there were no dose-related clinical adverse reactions observed with sitagliptin with doses of up to 600 mg per day for periods of up to 10 days and 400 mg per day for up to 28 days.

In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status.

Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3-to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

Simvastatin

Significant lethality was observed in mice after a single oral dose of 9 g/m². No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m², respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.

A few cases of overdosage with simvastatin have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae. Supportive measures should be taken in the event of an overdose. The dialyzability of simvastatin and its metabolites in man is not known at present.

You should not use this medicine if you are allergic to simvastatin or sitagliptin, if you have liver disease or severe kidney disease, or if you are pregnant or breast-feeding.

Do not use this medication if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

In rare cases, simvastatin and sitagliptin can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.

Some medicines can cause unwanted or dangerous effects when used with simvastatin and sitagliptin. Your doctor may need to change your treatment plan if you use any of the following drugs:

• cyclosporine;
• danazol;
• gemfibrozil;
• nefazodone;
• the antibiotics clarithromycin, erythromycin, or telithromycin;
• the antifungal medications itraconazole, ketoconazole, posaconazole, or voriconazole;
• the hepatitis C medications boceprevir or telaprevir; or
• the HIV/AIDS medications atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir, or tipranavir.

Before you start taking simvastatin and sitagliptin, tell your doctor if you are already using any of these other medicines:

• amiodarone or dronedarone;
• amlodipine;
• diltiazem;
• ranolazine; or
• verapamil.

To make sure simvastatin and sitagliptin is safe for you, tell your doctor if you have:

• a history of liver or kidney disease;
• a history of pancreatitis;
• a history of gallstones;
• underactive thyroid; or
• a history of alcoholism.

FDA pregnancy category X. This medication can harm an unborn baby or cause birth defects. Do not take simvastatin and sitagliptin if you are pregnant. Stop taking the medicine and tell your doctor right away if you become pregnant. Use effective birth control to avoid pregnancy while you are taking simvastatin and sitagliptin.

It is not known whether this medication passes into breast milk or if it could harm a nursing baby. Do not breast-feed while you are taking simvastatin and sitagliptin.

Do not give this medication to anyone under 18 years old without medical advice.

Sitagliptin and simvastatin combination is used together with a proper diet and exercise to treat type 2 diabetes. It is also used together with a proper diet to treat high cholesterol and triglyceride (fats) levels in the blood. sitagliptin and simvastatin may help prevent medical problems caused by clogged blood vessels such as heart attacks and strokes.

Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. It helps to control blood sugar levels by increasing substances in the body that make the pancreas release more insulin. It also signals the liver to stop producing sugar (glucose) when there is too much sugar in the blood.

Simvastatin belongs to the group of medicines called statins. It works to reduce the amount of cholesterol in the blood by blocking the production of cholesterol.

sitagliptin and simvastatin was available only with your doctor's prescription. The Juvisync™ product will no longer be marketed in the United States as of September 26, 2013, but may be available in other countries.

• If you have an allergy to sitagliptin, simvastatin, or any other part of sitagliptin and simvastatin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Acidic blood problem or type 1 diabetes.
• If you have any of these health problems: Active liver disease or a rise in liver enzymes.
• If you have kidney disease.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with this medicine, like certain drugs that are used for HIV, infections, or depression. There are many drugs that must not be taken with sitagliptin and simvastatin. Your doctor or pharmacist can tell you if you are taking a drug that must not be taken with this medicine.
• If you are pregnant or may be pregnant. Do not take sitagliptin and simvastatin if you are pregnant.
• If you are breast-feeding. Do not breast-feed while you take this medicine.

This is not a list of all drugs or health problems that interact with sitagliptin and simvastatin.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

(sit a GLIP tin & sim va STAT in)

• Antidiabetic Agent, Dipeptidyl Peptidase 4 (DPP-4) Inhibitor
• Antilipemic Agent, HMG-CoA Reductase Inhibitor

Administer in the evening. Do not split or divide tablet.

Sitagliptin:

Urine for glucose and ketones; blood glucose; hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals, quarterly in patients not meeting treatment goals or with therapy change [ADA 2017a]); renal function (prior to initiation and periodically during treatment); signs/symptoms of pancreatitis; joint pain.

Simvastatin:

2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013):

Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4 to 12 weeks after initiation or dose adjustment and every 3 to 12 months (as clinically indicated) thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.

Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure hepatic function if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.

CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).

If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.

Manufacturer's labeling: Upon initiation or titration, lipid panel should be analyzed after ≥4 weeks of therapy and periodically thereafter.