Juvisync, is an FDC ( fixed-dose combination ) of the two medications, Sitagliptin and Simvastatin). Sitagliptin and Simvastatin have been previously approved medications to separately treat elevated sugar and high cholesterol respectively.

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with Sitagliptin. These include anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with Sitagliptin, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue Juvisync, assess for other potential causes for the event, and institute alternative treatment. Angioedema has also been reported with other dipeptidyl peptidase-4 ( DPP-4 ) inhibitors. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with Juvisync.

In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in greater than 5% of patients treated with Sitagliptin as monotherapy and in combination therapy and more commonly than in patients treated with placebo, were upper respiratory tract infection ( Sitagliptin, 15.5%; placebo, 6.2% ); nasopharyngitis ( 11.0%,9.3% ); peripheral edema ( 8.3%, 5.2% ), and headache ( 5.5%, 4.1% ).

Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness, or weakness with creatine phosphokinase ( CK ) levels above 10 × ULN. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of statin activity in plasma. Predisposing factors for myopathy include advanced age ( greater than 65 years ), female gender, uncontrolled hypothyroidism, and renal impairment.

Because of the increased risk of myopathy / rhabdomyolysis, particularly at higher doses of Simvastatin, concomitant use of Juvisync is contraindicated with drugs that are strong CYP3A4 inhibitors or with Gemfibrozil, Cyclosporine or Danazol, and large quantities of grapefruit juice ( greater than 1 quart daily ) should be avoided. Use caution when prescribing Juvisync with other fibrates or Colchicine. The dose of Juvisync should not exceed 100/10 mg daily in patients receiving concomitant therapy with Verapamil or Diltiazem, and 100/20 mg daily in patients receiving Amiodarone, Amlodipine or Ranolazine. The use of Simvastatin with these drugs, or with lipid-lowering doses of Niacin, should be carefully weighed against the potential risk of myopathy / rhabdomyolysis with these combinations. Caution should be used when treating Chinese patients with Juvisync 100 mg/40 mg per day coadministered with lipid-modifying doses of niacin-containing products. It is recommended that adjusting the dose of Juvisync be considered during concomitant use with Voriconazole to reduce the risk of myopathy / rhabdomyolysis.

It is recommended that liver function tests be performed before the initiation of treatment, and thereafter when clinically indicated. Persistent increases ( greater than 3 times ULN ) in serum transaminases have occurred in approximately 1% of patients who received Simvastatin in clinical studies.

In clinical trials of Simvastatin, the most commonly reported side effects, regardless of cause, included upper respiratory infections ( 9.0% ), headache ( 7.4% ), abdominal pain ( 7.3% ), constipation ( 6.6% ), and nausea ( 5.4% ).

Source: Merck, 2011

XagenaMedicine2011