Ertugliflozin

An increased incidence of bone fractures has been observed with other sodium-glucose cotransporter 2 (SGLT2) inhibitors in some clinical trials. However, meta-analyses of trial data for canagliflozin, dapagliflozin, and empagliflozin have not demonstrated increased risk of fracture overall (Ruanpeng 2017; Tang 2016). One placebo-controlled trial with ertugliflozin did not show changes in bone mineral density (BMD) after 26 weeks, but additional longer-term data are required to more accurately define fracture risk (Rosenstock 2017).

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.

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 SGLT2 inhibitors; in some cases, patients have presented with normal or only modestly elevated blood glucose (• Lipid abnormality: May cause dose-related LDL-C elevation; monitor LDL-C and treat as needed.

An increased risk for lower limb amputation (primarily of the toe) has been observed with another SGLT2 inhibitor. In clinical trials, the incidence of non-traumatic lower limb amputations observed with ertugliflozin was ≤0.5% though a causal relationship has not been confirmed. Prior to initiation consider risk factors for amputation including prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients about the importance of preventative foot care. Monitor for, and discontinue therapy if any of the following occur: Signs and symptoms of new infection (including osteomyelitis), new pain or tenderness, or sores/ulcers involving the lower limbs.

Acute kidney injury has been reported. Prior to initiation, consider risk factors for acute kidney injury (eg, hypovolemia, chronic renal insufficiency, heart failure, use of concomitant medications [eg, diuretics, ACE inhibitors, angiotensin receptor blockers, 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:

Not recommended for use in 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. Use is not recommended when eGFR is persistently 30 to 2 due to lack of efficacy, and use is contraindicated in patients with an eGFR 2, ESRD, or maintained on dialysis. 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, dehydration) and renal impairment or failure. Other warnings/precautions:

Not for use in patients with diabetic ketoacidosis (DKA) or patients with type 1 diabetes mellitus.