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Merck has announced today that the FDA ( Food and Drug Administration ) has approved Juvisync ( Sitagliptin and Simvastatin ), a new treatment for type 2 diabetes that combines the glucose-lowering medication Sitagliptin, the active component of Januvia ( Sitagliptin ), with the cholesterol-lowering medication Zocor ( Simvastatin ).

Indications and usage

Juvisync is indicated in patients for whom treatment with both Sitagliptin and Simvastatin is appropriate. Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

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 non-pharmacologic 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, and 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 ); 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 ); to reduce elevated TG in patients with hypertriglyceridemia ( Fredrickson type lV hyperlipidemia ); to reduce elevated TG and VLDL-C in patients with primary dysbetalipoproteinemia ( Fredrickson type lll hyperlipidemia ); and to 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.

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 of developing pancreatitis while taking Juvisync.
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 moderate or severe renal impairment ( CrCl less than 50 mL/min, approximately corresponding to serum creatinine levels of greater than 1.7 mg/dL in men and greater than 1.5 mg/dL in women ) or end-stage renal disease ( ESRD ) are not available in this combination product, Juvisync is not recommended in patients with moderate or severe renal impairment or ESRD.

Safety information

Juvisync is contraindicated in patients with a history of a serious hypersensitivity reaction, such as anaphylaxis or angioedema, to any component of this medication; concomitant administration of strong CYP3A4 inhibitors ( e.g., Itraconazole, Ketoconazole, Posaconazole, HIV protease inhibitors, Erythromycin, Clarithromycin, Telithromycin and Nefazodone ); concomitant administration of Gemfibrozil, Cyclosporine, or Danazol; active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels; women who are pregnant or may become pregnant; and nursing mothers. Juvisync should be administered to women of childbearing age only when such patients are highly unlikely to conceive.

There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking Sitagliptin. After initiation of Juvisync, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, Juvisync should be promptly discontinued and appropriate management initiated. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking Juvisync.

The risk of myopathy, including rhabdomyolysis, is dose related. All patients starting therapy with Juvisync, or whose dose of Simvastatin is being increased, should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness. Juvisync therapy should be discontinued immediately if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Juvisync therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis.

Increases in A1C and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including Simvastatin.

Persistent increases ( to more than 3X the ULN ) in serum transaminases have occurred in approximately 1% of patients who received Simvastatin in clinical studies. It is recommended that liver function tests be performed before the initiation of treatment, and thereafter when clinically indicated. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including Simvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Juvisync, promptly interrupt therapy.

When Sitagliptin was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.

Assessment of renal function is recommended prior to initiating Juvisync and periodically thereafter. Juvisync is not recommended for use in patients with moderate or severe renal impairment or end-stage renal disease because doses of Juvisync appropriate for patients with moderate or severe renal impairment or ESRD are not available in this combination product.

There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis, in patients treated with Sitagliptin. A subset of these reports involved patients with renal impairment, some of whom were prescribed inappropriate doses of Sitagliptin. A return to baseline levels of renal impairment has been observed with supportive treatment and discontinuation of potentially causative agents.

The dosages for therapy with Juvisync are 100/10, 100/20, and 100/40 ( mg Sitagliptin / mg Simvastatin ) once daily. Juvisync should be taken as a single daily dose in the evening. Juvisync should be swallowed whole. The tablets must not be split, crushed, or chewed before swallowing.
The recommended starting dose is 100/40 mg/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 four or more weeks and dosage adjusted, if needed.  ( Xagena )

Source: Merck, 2011

XagenaMedicine2011