The Food and Drug Administration on Oct. 7 announced the approval of a combination pill containing fixed doses of sitagliptin and simvastatin for people in whom treatment with both drugs is indicated.
The combination product, which will be marketed as Juvisync, is the first product that combines in a single tablet a drug approved for treating type 2 diabetes with a cholesterol-lowering drug, according to an agency statement announcing the approval.
Sitagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor approved for use in combination with diet and exercise to improve glycemic control in adults with type 2 diabetes; it is marketed as Januvia (and as Janumet in combination with metformin). Simvastatin is an HMG-CoA reductase inhibitor approved for use with diet and exercise to lower low-density lipoprotein cholesterol and is marketed as Zocor and is available in generic formulations (and in combination with niacin and with ezetimibe).
Approval of Juvisync is based on the "substantial experience" with both drugs separately, "and the ability of the single tablet to deliver similar amounts of the drugs to the bloodstream as when sitagliptin and simvastatin are taken separately," according to the statement, which describes Juvisync as a "convenience combination" that should only be prescribed "when it is appropriate for a patient to be placed on both of these drugs."
"To ensure safe and effective use of this product, tablets containing different doses of sitagliptin and simvastatin in fixed-dose combination have been developed to meet the different needs of individual patients," Dr. Mary H. Parks, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research said in the statement.
The approved dosage strengths of the sitagliptin/simvastatin combination are 100 mg/10 mg, 100 mg/20 mg, and 100 mg/40 mg, all of which are taken as a single dose in the evening, according to the prescribing information.
The manufacturer has committed to developing combined tablets containing the 50 mg sitagliptin dose, with 10 mg, 20 mg and 40 mg of simvastatin, but until these are available, patients who need the 50-mg dose of sitagliptin should be prescribed the single-ingredient tablet. There are no plans to develop a combination tablet with the 25-mg sitagliptin dose, which is not used very much, or with the 80-mg dose of simvastatin, because of recent restrictions on the use of this dose because it is associated with an increased risk of muscle toxicity, the statement said.
The statement says that the agency has recently become aware of the potential for statins to increase serum glucose levels in patients with type 2 diabetes, although the risk "appears very small and is outweighed by the benefits of statins for reducing heart disease in diabetes." To assess this risk further, the FDA is requiring that the manufacturer conduct a postmarketing clinical study. The FDA’s approval letter for Juvisync says that the trial should be a randomized, double-blind, active-controlled study that compares the effect of sitagliptin and simvastatin fixed-dose combination with sitagliptin on glycemic control in type 2 diabetic patients on background metformin therapy.
Juvisync is manufactured by MSD International GmbH Clonmel Co., based in Tipperary, Ireland.