Tablets: ertugliflozin 7.5 mg and metformin hydrochloride 1000 mg, red, oval, debossed with "7.5/1000" on one side and plain on the other side.

 

4 CONTRAINDICATIONS 

  

Severe renal impairment, end stage renal disease (ESRD), or patients on dialysis [see Warnings and Precautions (5.1, 5.4) and Use in Specific Populations (8.6)].

Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.

History of a serious hypersensitivity reaction to SEGLUROMET, ertugliflozin, or metformin hydrochloride.

 

5 WARNINGS AND PRECAUTIONS 

 

5.1 Lactic Acidosis

 

There have been post-marketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate:pyruvate ratio; metformin plasma levels were generally >5 mcg/mL. Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk.

 

If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of SEGLUROMET. In SEGLUROMET-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to 170 mL/minute under good hemodynamic conditions). Hemodialysis has often resulted in reversal of symptoms and recovery.

 

Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to discontinue SEGLUROMET and report these symptoms to their healthcare provider.

 

For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below:

 

Renal Impairment: The postmarketing metformin-associated lactic acidosis cases primarily occurred in patients with significant renal impairment. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney [see Warnings and Precautions (5.4) and Clinical Pharmacology (12.3)].

Before initiating SEGLUROMET, obtain an eGFR.

SEGLUROMET is contraindicated in patients with an eGFR less than 30 mL/minute/1.73 m2. 

Initiation of SEGLUROMET is not recommended in patients with an eGFR of 30 mL/minute/1.73 m2 to less than 60 mL/min/1.73 m2.

Continued use of SEGLUROMET is not recommended when eGFR is persistently between 30 and less than 60 mL/min/1.73 m2.