sax-a-GLIP-tin

Therapeutic Classification: antidiabetics

Pharmacologic Classification:

• Type 2 diabetes mellitus (as adjunct to diet and exercise).

• Acts as a competitive inhibitor of dipeptidyl peptidase-4 (DPP4), which slows inactivation of incretin hormones, thereby increasing their concentrations and reducing fasting and postprandial glucose concentrations.

• Improved control of blood glucose.

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4/5 isoenzyme, with conversion to 5-hydroxysaxagliptin, a pharmacologically active metabolite; 24% of saxagliptin is excreted unchanged in urine, 36% of hydroxysaxagliptin is excreted unchanged in urine, 22% is eliminated in feces as unabsorbed drug/metabolites excreted in bile.

Half-life: Saxagliptin: 2.5 hr; 5-hydroxysaxagliptin: 3.1 hr.

(DPP-4 inhibition)

†Blood levels.

Contraindicated in:

• Type 1 diabetes
• Diabetic ketoacidosis
• History of hypersensitivity reaction.

Use Cautiously in:

• HF or renal impairment (↑ risk of worsening HF)
• Moderate or severe renal impairment (CCr 45 mL/min) (↓ dose required)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Use while breastfeeding only if potential maternal benefit outweighs potential risk to infant
• Pedi: Safety and effectiveness not established in children
• Geri: Older adults may be more sensitive to effects; consider age-related ↓ in renal function.

CV: HF, peripheral edema (↑ with thiazolidinediones).

Derm: bullous pemphigoid.

Endo: hypoglycemia (↑ with sulfonylureas).

GI: abdominal pain, PANCREATITIS, vomiting.

Hemat: ↓lymphocyte count.

MS: arthralgia, RHABDOMYOLYSIS.

Neuro: headache.
Misc: (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)HYPERSENSITIVITY REACTIONS .

Drug-Drug:

• Strong CYP3A4/5 inhibitors, including ketoconazole, atazanavir, clarithromycin, itraconazole, nefazodone, nelfinavir, and ritonavir, ↑ levels and risk of toxicity.
• ↑risk of hypoglycemia with sulfonylureas or insulin; may need to ↓ dose of sulfonylureas or insulin.

• PO (Adults): 2.5–5 mg once daily; Concurrent use of strong CYP3A4/5 inhibitors: 2.5 mg once daily.

(Generic available)

• Tablets: 2.5 mg; 5 mg;
• In combination with: dapagliflozin (Qtern); metformin XR (generic only). See Appendix [not included in this PDA edition].

• Observe patient for signs and symptoms of hypoglycemic reactions (abdominal pain, sweating, hunger, weakness, dizziness, headache, tremor, tachycardia, anxiety).
• Monitor for signs of pancreatitis (nausea, vomiting, anorexia, persistent severe abdominal pain, sometimes radiating to the back) during therapy. If pancreatitis occurs, discontinue saxagliptin and monitor serum and urine amylase, amylase/creatinine clearance ratio, electrolytes, serum calcium, glucose, and lipase.

• Monitor hemoglobin A1c prior to and periodically during therapy.
  • Monitor renal function prior to and periodically during therapy.
  • May cause ↓ absolute lymphocyte count.

• Do not confuse saxagliptin with sitagliptin.
• Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
• PO: May be administered without regard to food. DNC: Swallow tablet whole; do not crush, cut, or split.

• Instruct patient to take saxagliptin as directed. If a dose is missed, take the next dose as prescribed; do not double doses. Advise patient to read the Patient Package Insert before starting and with each Rx refill; new information may be available.
• Explain to patient that saxagliptin helps control hyperglycemia but does not cure diabetes. Therapy is usually long term.
• Instruct patient not to share this medication with others, even if they have the same symptoms; it may harm them.
• Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hyperglycemic or hypoglycemic episodes.
• Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to take a glass of orange juice or 2–3 tsp of sugar, honey, or corn syrup dissolved in water, and notify health care professional.
• Instruct patient in proper testing of blood glucose and urine ketones. These tests should be monitored closely during periods of stress or illness and health care professional notified if significant changes occur.
• Advise patient to notify health care professional promptly if swelling of hands, feet, or ankles; rash; hives; or swelling of face, lips, or throat occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

• Improved hemoglobin A1c, fasting plasma glucose, and 2-hr postprandial glucose levels.

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