Brand Name: DIASIT
Generic Name: Sitagliptin
Preparations: 25/50/100 mg Tablets
Pharmacologic Categories: Antidiabetic, Dipeptidyl peptidase-4 inhibitor
Mechanism of Action (MOA)
DIASIT (Sitagliptin) inhibits dipeptidyl peptidase IV (DPP-IV) enzyme resulting in prolonged active incretin levels. Incretin hormones, including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), regulate glucose homoeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Reduced glucagon secretion leads to decreased hepatic glucose production.
Under normal physiologic circumstances, incretin hormones are released by the intestine throughout the day and levels are increased in response to a meal; incretin hormones are rapidly inactivated by the DPP-IV enzyme.
Pharmacokinetics
Absorption: Rapid
Bioavailability: Approximately 87%
Time to Peak: 1 to 4 hours
Protein Binding: 38%
Metabolism: Liver
Elimination Half-life: 12.4 hours
Excretion: 87% via urine and 13% via faeces
Indications and Dosage
Type 2 diabetes: 100 mg once daily
Dosing modifications in renal impairment
CrCl>50 mL/min: Dose adjustment is not necessary
CrCl 30-50 mL/min: 50 mg once daily
CrCl<30 mL/min: 25 mg once daily
ESRD: 25 mg once daily regardless of hemodialysis
Hepatic impairment
Mild to moderate impairment: Dose adjustment is not necessary
Severe impairment: Not studied
Side Effects
1-10%: Nasopharyngitis, diarrhoea, headache, constipation, peripheral oedema, nausea, pharyngitis, osteoarthritis, upper respiratory infection
<1%: Hypersensitivity reactions such as anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, exfoliative skin conditions including Stevens-Johnson syndrome; hepatic enzyme elevation; acute pancreatitis including fatal and non-fatal hemorrhagic and necrotizing pancreatitis; constipation; vomiting; worsening renal function including acute renal failure; severe and disabling arthralgia; myalgia; pain in extremity; back pain
POSTMARKETING REPORT: Pruritus
Contraindication
Hypersensitivity to Sitagliptin
Warnings/ Precautions
• Caution in hepatic impairment or heart failure.
• Caution in renal failure; worsening of renal failure including acute renal failure reported.
• Not for use in diabetic ketoacidosis patients, type 1 diabetes mellitus; not effective.
• Caution when co-administering with strong CYP3A4/5 inhibitors eg. Clarithromycin, itraconazole (may require dose adjustment).
• May cause acute pancreatitis including hemorrhagic and necrotizing pancreatitis; unknown if patients with a history of pancreatitis are at increased risk.
• Concomitant use of insulin with secretagogues may increase the risk of hypoglycemia.
• Angioedema reported with other DPP-4 inhibitors; caution with history of angioedema.
• Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate.
Drug Interactions
• DPP-4 inhibitors may enhance the adverse/toxic effect of ACE inhibitors.
• Alpha-lipoic acid may enhance the hypoglycemic effect of antidiabetic agents.
• Androgens, MAO inhibitors, pegvisomant, salicylates and SSRIs may enhance the hypoglycemic effect of blood glucose lowering agents.
• May increase the serum concentration of digoxin.
• Hyperglycemia-associated agents may diminish the therapeutic effect of antidiabetic agents whereas antidiabetic agents may enhance the hypoglycemic effect of hypoglycemia-associated agents.
• DPP-4 inhibitors may enhance the hypoglycemic effect of insulin and sulfonylureas.
• Thiazide and thiazide-like diuretics may diminish the therapeutic effect of antidiabetic agents.
Pregnancy Category: B
Presentations
DIASIT 25: 10 X 10’s
DIASIT 50: 10 X 10’s
DIASIT 100: 10 X 10’s
