sitagliptin (Rx)

1-10%

Nasopharyngitis (5%)

Diarrhea (4%)

Headache (3.6%)

Constipation (3%)

Peripheral edema (2%)

Nausea (2%)

Pharyngitis (1%)

Osteoarthritis (1%)

URI (1%)

Postmarketing Reports

Hypersensitivity reactions including 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

Worsening renal function, including acute renal failure (sometimes requiring dialysis)

Severe and disabling arthralgia

Constipation, vomiting

Headache, myalgia, pain in extremity, back pain

Rhabdomyolysis

Pruritus

Bullous pemphigoid

Mouth ulceration; stomatitis

Contraindications

Documented hypersensitivity

Cautions

Heart failure has been observed with two other members of the DPP-4 inhibitor class; consider risks and benefits of sitagliptin in patients with risk factors for heart failure; monitor for signs and symptoms; if heart failure develops, manage accordingly to standard of care and consider interrupting treatment

Bullous pemphigoid reported with DPP-4 inhibitor use, which required hospitalization; in reported cases, patients recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP-4 inhibitor; patients should report development blisters/erosions; discontinue DPP-4 therapy and consult a dermatologist if bullous pemphigoid suspected

Use with caution in hepatic impairment, or heart failure (due to an elevated overall risk of acute HF in those patients taking any dipeptidyl peptidase4 inhibitor)

Use with caution in renal failure; worsening of renal failure, including acute renal failure reported

Not for use in diabetic ketoacidosis patients; not effective

Not for use in type 1 diabetes mellitus; not effective

Combo treatment studied only with metformin and thiazolidinediones, not with insulin or sulfonylureas

Caution when coadministering with strong CYP3A4/5 inhibitors (may require dose adjustment)

May cause acute pancreatitis, including hemorrhagic and necrotizing pancreatitis; unknown if patients with history of pancreatitis are at increased risk

Concomitant use of insulin with secretagogues may increase risk of hypoglycemia

Angioedema reported with other dipeptidyl peptidase-4 (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

Caution should be used to ensure that correct dose is prescribed for patients with moderate (eGFR ≥30 to <45 mL/min/1.73 m²) or severe (eGFR <30 mL/min/1.73 m²) renal impairment

Pregnancy

There is pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; health care providers are encouraged to report any prenatal exposure to drug by calling the Pregnancy Registry at 1-800-986-8999

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Dipeptyl peptidase-IV (DPP-4) inhibitor; increases and prolongs incretin hormone activity, which is inactivated by DPP-4 enzyme

Incretins increase insulin release and synthesis from pancreatic beta cells and reduce glucagon secretion from pancreatic alpha cells

Absorption

Bioavailability: 87%

Peak plasma time: 1-4 hr

Distribution

Protein bound: 38%

Vd: 198 L

Metabolism

Limited; primarily via CYP3A4 and CYP2C8

Elimination

Half-life, terminal: 12.4 hr

Excretion: Urine (87%), feces (13%)

Instructions

Take with or without food

Swallow tablet whole; do not chew, crush, or split