Sitagliptin

Indications

Sitagliptin is used for: Type 2 diabetes mellitus

Adult Dose

Oral Type 2 diabetes mellitus Adult: 100 mg once daily. Hepatic impairment Mild to moderate impairment: Dose adjustment not necessary Severe impairment: Not studied

Child Dose

Safety and efficacy not established

Renal Dose

Renal impairment CrCl >50 mL/min: Dose adjustment not necessary CrCl 30-50 mL/min: 50 mg PO qDay CrCl <30 mL/min: 25 mg PO qDay ESRD: 25 mg PO qDay regardless of hemodialysis

Administration

May be taken with or without food.

Contra Indications

Hypersensitivity reactions such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome can occur. Type 1 diabetes. Diabetic ketoacidosis.

Precautions

Patient w/ type 1 diabetes, history of angioedema. Not intended for the treatment of diabetic ketoacidosis. Moderate and severe renal impairment. Pregnancy and lactation. Monitoring Parameters Monitor glycosylated Hb (HbA1c), serum glucose. Assess renal function prior to initiation of therapy and periodically thereafter. Lactation: Not known whether excreted in breast milk: use caution

Pregnancy-Lactation

Pregnancy Limited available data in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy; no adverse developmental effects were observed when sitagliptin was administered to pregnant rats and rabbits during organogenesis at oral doses up to 30-times and 20-times, respectively, the 100 mg clinical dose, based on AUC Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, still birth, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity Lactation There is no information regarding presence of drug in human milk, effects on breastfed infant, or on milk production; drug is present in rat milk and therefore possibly present in human; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from the underlying maternal condition

Interactions

Increased risk of hypoglycaemia when used in combination w/ sulfonylureas or insulin.

Adverse Effects

Side effects of Sitagliptin : 1-10% Nasopharyngitis (5%), Diarrhea (4%), Headache (3.6%), Constipation (3%), Peripheral edema (2%), Nausea (2%), Pharyngitis (1%), Osteoarthritis (1%), URI (1%) <1% Hypersensitivity reactions such as anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, and exfoliative skin conditions (including Stevens-Johnson syndrome) Hepatic enzyme elevations, Acute pancreatitis, including fatal and nonfatal hemorrhagic and necrotizing pancreatitis.Constipation.Vomiting.Worsening renal function, including acute renal failure (sometimes requiring dialysis), Severe and disabling arthralgia, Myalgia, Pain in extremity, Back pain

Mechanism of Action

Sitagliptin inhibits dipeptidyl peptidase IV (DPP-IV), resulting in prolonged active incretin levels. Incretin hormones increases insulin synthesis and release from pancreatic beta-cells and reduces glucagon secretion from pancreatic beta-cells. Reduced glucagon secretion leads to decreased hepatic glucose production.