Simvastatin/sitagliptin

Simvastatin/sitagliptin
Combination of
Simvastatin hypolipidemic statin
Sitagliptin antidiabetic DPP-4 inhibitor
Clinical data
Trade names Juvisync
AHFS/Drugs.com Consumer Drug Information
Pregnancy
category
  • US: X (Contraindicated)
Legal status
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Simvastatin/sitagliptin (brand name Juvisync) is a fixed-dose combination drug consisting of sitagliptin and simvastatin. Sitagliptin is a dipeptidyl peptidase-4 inhibitor used to treat type 2 diabetes and simvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemia.[1] These two disorders commonly occur in patients at the same time, and have been typically treated with administration of these two drugs in separate tablets. The combination was approved in 2011 and is marketed as Juvisync by Merck. Juvisync was later removed from the market in 2013 due to business reasons.[2]

History

In 1991, Merck & Co’s simvastatin was approved as an HMG-COA inhibitor to lower the levels of LDL cholesterol. In 2006, Merck & Co’s sitagliptin was approved by the FDA for treatment of diabetes mellitus type 2.[3] The patent for simvastatin expired in 2006 and many companies began to create a generic product of simvastatin. By creating a combined-dosage form of simvastatin and sitagliptin, Merck was able to increase their sales of simvastatin while meeting the need of patients who take both simvastatin and sitagliptin.

Regulation

Juvisync was the first product to combine a cholesterol lowering drug with a type 2 diabetes drug in the same tablet.[4] Due to the potential for patients to need different doses of the two drugs, different dosage strengths were approved. These doses are for sitagliptin/simvastatin of 100 mg/10 mg, 100 mg/20 mg, 100 mg/40 mg, 50 mg/10 mg, 50 mg/20 mg, or 50 mg/40 mg.[5]

Nonclinical Toxicology

Sitagliptin: Using male and female rats, a two year carcinogenicity study was carried out with doses of 50, 150, and 500 mg/kg/day. The 500 mg/kg dose has exposure limits of 60 times what would be seen in the highest dose in humans. At this dose, liver adenoma/carcinoma was seen. Tumors were not seen from the smaller doses. Nomutagenic or clastogenic effects were seen from tests using several assays (CHO, rat, etc.). Fertility studies in rats showed no teratogenic effects.[6]

Simvastatin: No tumorigenic effect was seen in a 72-week carcinogenicity study using mice at the low dose levels. However, at the higher dose levels (8 and 16 times the human dose equivalent), liver carcinomas and adenomas, lung adenomas, and adenomas of the Harderian gland. No mutagenic effects were seen in assays. There was testicular atrophy noted in dogs and rats at 4 and 8 times the human exposure, respectively.[7]

Limitations of Use

Should not be used in patients with the following: type 1 diabetes, diabetic ketoacidosis, pancreatitis, Fredrickson types I and V dyslipidemias, and severe renal impairment.[8]

Drug Interactions

Juvisync should not be used with: strong CYP3A4 inhibitors, cyclosporine, danazol, gemfibrozil and other fibrates.[9] Caution should be used and the patient should be monitored if they are taking the following: amiodarone, dronedarone, ranolazine, calcium channel blockers, niacin, digoxin, coumarin anticoagulants, and colchicine.[10]

References

  1. ↑ "FDA Approves Juvisync, Combination of Sitagliptin and Simvastatin". Forbes. October 7, 2011.
  2. ↑ U.S. Food and Drug Administration. "Drugs to be Discontinued". Retrieved 2013-12-11.
  3. ↑ Alvey, Laura (2006-10-17). "FDA Approves New Treatment for Diabetes: First in a New Class of Diabetes Drugs". FDA News Release. Retrieved 2013-12-11.
  4. ↑ Liscinsky, Morgan (2011-10-07). "FDA Approves Combination Therapy Juvisync". FDA News Release. Retrieved 2013-12-11.
  5. ↑ Food and Drug Administration. "Highlights of Prescribing Information" (PDF). Retrieved 2013-12-11.
  6. ↑ Food and Drug Administration. "Highlights of Prescribing Information" (PDF). Retrieved 2013-12-11.
  7. ↑ Food and Drug Administration. "Highlights of Prescribing Information" (PDF). Retrieved 2013-12-11.
  8. ↑ Food and Drug Administration. "Highlights of Prescribing Information" (PDF). Retrieved 2013-12-11.
  9. ↑ RxList: The Internet drug Index. "Juvisync Indications & Dosage". Retrieved 2013-12-11.
  10. ↑ RxList: The Internet drug Index. "Juvisync Side Effects & Drug Interactions". Retrieved 2013-12-11.
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