Adult Dosing
Type 2 diabetes mellitus, hypertriglyceridemia or prevention of cardiovascular events
- Usual dosage: 100 mg/10 mg, 100 mg/20 mg, and 100 mg/40 mg (sitagliptin/simvastatin) PO qpm
- Recommended starting dose: 100 mg/40 mg (sitagliptin/simvastatin) PO qpm
- For patients already on simvastatin (10, 20, or 40 mg qd): Start with sitagliptin 100 mg daily and the dose of simvastatin already being taken
- Analyze lipid levels after 4 or more wks after therapy initiation and adjust the dose if needed
Patients with homozygous familial hypercholesterolemia
- Recommended dose: 100 mg/40 mg (sitagliptin/simvastatin) PO qpm
Coadministration with other drugs
- Verapamil, diltiazem or Dronedarone
- Do not exceed 100 mg/10 mg (sitagliptin/simvastatin) PO qd
- Amiodarone, amlodipine or ranolazine
- Do not exceed 100 mg/20 mg (sitagliptin/simvastatin) PO qd
- Chinese Patients taking
1 g/day of niacin - Cautiously administer 100 mg/40 mg PO (sitagliptin/simvastatin) qd
Note:
- Tablets should be swallowed whole; do not split, crush, or chew tablet before swallowing
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
See Supplemental Patient Information
- Post-marketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, have been reported in patients receiving this therapy. Carefully monitor patients for signs and symptoms of pancreatitis; if pancreatitis is suspected, promptly discontinue the medication and initiate appropriate therapy
- Myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) more than ten times the upper limit of normal (ULN) and sometimes as rhabdomyolysis with or without acute renal failure have been reported with the use of this therapy. Consider periodic CK determinations in patients starting this therapy
- Advanced age (65 years), female gender, uncontrolled hypothyroidism, and renal impairment are the predisposing factors for myopathy. High levels of statin activity in plasma also increases the risk of myopathy
- Before initiating sitagliptin/simvastatin therapy, inform all patients about the risk of myopathy and rhabdomyolysis and advise them to promptly report any unexplained muscle pain, tenderness or weakness. Discontinue the drug immediately if myopathy is suspected or diagnosed
- The incidence of myopathy, including rhabdomyolysis, was significantly higher in patients taking 80 mg of simvastatin as compared to the lower doses and other statin therapies with similar or greater LDL-C-lowering efficacy. Also, an increased incidence of myopathy and rhabdomyolysis was noted during the first year of treatment with simvastatin 80 mg and decreased notably during the subsequent years of treatment
- Analyze lipid levels after 4 weeks of therapy and periodically thereafter. Monitor CK levels periodically during therapy
- Strong CYP3A4 inhibitors (itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, or large quantities of grapefruit juice) should not be used concomitantly, as they may increase the plasma levels of simvastatin resulting in increased risk of myopathy
- Persistent increases in serum transaminases levels (>3 x ULN) have been reported with simvastatin component of this combination drug. Perform liver function tests before initiation of treatment, before titration of dose to 80 mg/day, 3 months after titration, and periodically thereafter. Withdraw therapy if AST or ALT levels >3 x ULN. Use cautiously in patients with a past history of liver disease or who consume substantial quantities of alcohol
- Sitagliptin/simvastatin therapy is not recommended in patients with moderate or severe renal insufficiency or in those with ESRD requiring hemodialysis or peritoneal dialysis. Assess renal function prior to and regularly during treatment
- There is an increased risk of hypoglycemia when co-administered with an insulin secretagogue (e.g., sulfonylurea) or insulin therapy. Consider lowering the dose of sulfonylurea or insulin to reduce the risk of hypoglycemia
- Post-marketing reports of serious hypersensitivity reactions such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome have been reported during therapy. In such cases, promptly discontinue therapy, assess for other potential causes, institute appropriate monitoring and treatment, and initiate alternative treatment
- HMG-CoA reductase inhibitors, including simvastatin, may increase A1C and fasting serum glucose levels
Cautions: Use cautiously in
- Mild renal impairment
- History of liver diseases
- Elderly patients
- History of pancreatitis
- Hx of angioedema with another DPP-4 inhibitor
- Chinese patients
- Alcohol abuse
- Grapefruit juice
Supplemental Patient Information
- Inform patients of the potential risk of myopathy, including rhabdomyolysis associated with this therapy; advise them to promptly report any unexplained muscle pain, tenderness or weakness
- Inform patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and A1C testing
- Advise women of childbearing age to use an effective method of birth control to prevent pregnancy while on therapy; instruct them to stop therapy and immediately inform their health professional if they become pregnant during therapy
Pregnancy Category:X
Breastfeeding: Sitagliptin: Because no information is available regarding its use during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Simvastatin: Limited published data exist to define the safety of breastfeeding during its use. Due to a concern with disruption of infant lipid metabolism, simvastatin should not be used in nursing mothers. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 7 November 2011). Small amount of another drug belonging to the same class as simvastatin is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, manufacturer recommends to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
US Trade Name(s)
US Availability
Juvisync (sitagliptin/simvastatin)
- TABS
- 100 mg/10 mg
- 100 mg/20 mg
- 100 mg/40 mg
- 50 mg/10 mg
- 50 mg/20 mg
- 50 mg/40 mg
Canadian Trade Name(s)
Canadian Availability
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
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