Dapagliflozin

An increased incidence of bone fractures has been observed with dapagliflozin in patients with moderate renal impairment (eGFR 30 to 60 mL/minute/1.73 m2).

May increase the risk of genital mycotic infections (eg, vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis, candida balanitis, balanoposthitis). Patients with a history of these infections or uncircumcised males are at greater risk.

Patients may experience hypersensitivity reactions (eg, angioedema, urticaria), with some being severe. Discontinue dapagliflozin if hypersensitivity occurs and treat as appropriate.

May cause symptomatic hypotension due to intravascular volume depletion, especially in patients with renal impairment (ie, eGFR 2), elderly, patients on other antihypertensives (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]), or those with low systolic blood pressure. Assess volume status prior to initiation in patients at risk of hypotension and correct if depleted; monitor for signs and symptoms of hypotension after initiation.

Cases of ketoacidosis (some fatal) have been reported in patients with type 1 and type 2 diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors; in some cases, patients have presented with normal or only modestly elevated blood glucose (• Lipid abnormality: May cause LDL-cholesterol (C) elevation; monitor LDL-C and treat as needed.

Acute kidney injury has been reported. Prior to initiation, consider risk factors for acute kidney injury (eg, hypovolemia, chronic renal insufficiency, HF, use of concomitant medications [eg, diuretics, ACE inhibitors, angiotensin receptor blockers, or NSAIDs]). Temporarily discontinue use with reduced oral intake or fluid losses; discontinue use if acute kidney injury occurs. Additional abnormalities in renal function (decreased eGFR, increased serum creatinine) and adverse effects related to renal function may occur. Assess renal function prior to initiation and periodically during treatment.

Serious urinary infections including urosepsis and pyelonephritis requiring hospitalization have been reported; treatment with SGLT2 inhibitors increases the risk for urinary tract infections (UTI); monitor for signs and symptoms of UTI and treat as needed. Disease-related concerns:

Newly diagnosed bladder cancer occurred more frequently in dapagliflozin patients; causal relationship could not be established. Do not use in patients with active bladder cancer; weigh the benefits of glycemic control versus the unknown risks for cancer recurrence in patients with a history of bladder cancer.

Weigh benefits versus risk in patients with severe hepatic impairment (has not been studied).

Glycemic efficacy may be decreased in renal impairment. Assess renal function prior to initiation and periodically during treatment. Dapagliflozin should not be initiated in patients with eGFR 2 and should be discontinued when eGFR is persistently 2. Use is contraindicated in severe renal impairment (eGFR 2), ESRD, and in dialysis patients. 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. Special populations:

Elderly patients may be predisposed to symptoms related to intravascular volume depletion (eg, hypotension, orthostatic hypotension, dizziness, syncope, and dehydration) and renal impairment or failure. Other warnings/precautions:

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