SYNJARDYXR(empagliflozin and metformin hydrochloride extended-release) tablets(五)
Boehringer Ingelheim company logo and “S25” on the top line and “1000 M” on the bottom line.
4 CONTRAINDICATIONS
SYNJARDY XR is contraindicated in patients with:
Moderate to severe renal impairment (eGFR less than 45 mL/min/1.73 m2), end stage renal disease, or dialysis [see WARNINGS AND PRECAUTIONS (5.1, 5.4) and USE IN SPECIFIC POPULATIONS (8.6)].
Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin [see WARNINGS AND PRECAUTIONS (5.1)].
History of serious hypersensitivity reaction to empagliflozin or metformin.
5 WARNINGS AND PRECAUTIONS
5.1 Lactic Acidosis
There have been postmarketing 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 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 SYNJARDY XR. In SYNJARDY XR-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin 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 SYNJARDY XR 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 CLINICAL PHARMACOLOGY (12.3)].
Before initiating SYNJARDY XR, obtain an estimated glomerular filtration rate (eGFR).
SYNJARDY XR is contraindicated in patients with an eGFR below 45 mL/min/1.73 m2.
Obtain an eGFR at least annually in all patients taking SYNJARDY XR. In patients at increased risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently.
Drug Interactions: The concomitant use of SYNJARDY XR with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid |
