Saxagliptin

Severe and disabling arthralgia has been reported with DPP-IV inhibitor use; onset may occur within one day to years after treatment initiation and may resolve with discontinuation of therapy. Some patients may experience a recurrence of symptoms if DPP-IV inhibitor therapy resumed.

DPP-4 inhibitor use has been associated with development of bullous pemphigoid; cases have typically resolved with topical or systemic immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Advise patients to report development of blisters or erosions. Discontinue therapy if bullous pemphigoid is suspected and consider referral to a dermatologist.

Dose-related decrease in lymphocyte count has been observed; clinical significance is not known. Monitoring of lymphocyte counts may be warranted in patients with unusual or persistent infection.

Hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative dermatologic reactions have been reported; discontinue if signs/symptoms of severe hypersensitivity reaction occur. Events have generally occurred within the first 3 months of therapy, and may occur after the initial dose. Use with caution if patient has experienced angioedema with other DPP-IV inhibitor use.

Cases of acute pancreatitis have been reported with use. Monitor for signs/symptoms of pancreatitis; discontinue use immediately if pancreatitis is suspected and initiate appropriate management. Use with caution in patients with a history of pancreatitis as it is not known if this population is at greater risk. Disease-related concerns:

Heart failure that may require hospitalization has been reported in a multi-center, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes with a history of, or at risk for, cardiovascular events; risk was increased in patients with preexisting heart failure or renal impairment and during the first 12 months of therapy (Scirica 2013; Scirica 2014). However, a population-based retrospective study in an ambulatory setting with relatively lower baseline cardiovascular risk factors failed to demonstrate increased risk in patients on saxagliptin compared to other agents (eg, sitagliptin, pioglitazone, sulfonylureas, insulin) (Toh 2016). Monitor for signs and symptoms of heart failure during therapy and consider discontinuation if condition develops. In a scientific statement from the American Heart Association, saxagliptin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).

Use with caution in patients with moderate to severe renal dysfunction (eGFR 2) including end-stage renal disease (ESRD) requiring hemodialysis; dosing adjustment required. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Not indicated for use in patients with type 1 diabetes mellitus (insulin dependent, IDDM) or with diabetic ketoacidosis (DKA).

Diabetes self-management education (DSME) is essential to maximize the effectiveness of therapy.