Sitagliptin/Simvastatin: a first combination tablet to treat type 2 diabetes and hypercholesterolemia – a review of its characteristics

Figures & data

Figure 1 Structural formula for sitagliptin.

Figure 2 Structural formula for simvastatin.

Table 1 Pharmacokinetics

	Absorption	Distribution	Metabolism	Elimination
Simvastatin	Tmax 4 hours Bioavailability <5%	95% bound to plasma proteins	Undergoes extensive first-pass metabolism in the liver via CYP3A4	60% eliminated in the feces; 13% in the urine; 27% eliminated through other mechanisms
Sitagliptin	Tmax 1–4 hours Bioavailability 87%	38% bound to plasma proteins	Minimally metabolized via CYP3A4 and CYP2C8 to inactive metabolites	87% eliminated in the urine (79% as unchanged drug, 8% as metabolites); 13% in feces

Abbreviations: T_max, time to peak plasma concentration; CYP, cytochrome P450.

Table 2 Drug interactions associated with increased risk of myopathy/rhabdomyolysis

Interacting agents	Prescribing recommendations
Itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, human immunodeficiency virus protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol	Contraindicated with Juvisync
Verapamil, diltiazem	Do not exceed 100 mg/10 mg Juvisync daily
Amiodarone, amlodipine, ranolazine	Do not exceed 100 mg/20 mg Juvisync daily
Grapefruit juice	Avoid large quantities of grapefruit juice (more than 950 mL daily)

Table 3 Special populations and Juvisync

Special populations	Comments
Pediatric (aged <18 years)	Safety and efficacy of Juvisync has not been established in this population
Geriatric	Considering the higher risk of myopathy and renal failure in this population, caution is warranted upon using Juvisync
Pregnancy/lactation	Use of Juvisync is contraindicated in this population
Renal impairment	Juvisync is not recommended in moderate or severe renal impairment
Hepatic impairment	Juvisync is contraindicated in patients with active liver disease or persistent unexplained elevated liver enzymes