Glyburide-Metformin Hydrochloride

⛔ FDA Black Box Warning

WARNING: LACTIC ACIDOSIS WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metforminassociated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL [ see Warnings and Precautions ( 5.1 ) ]. Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [ see Dosage and Administration ( 2.3 ), Contraindications ( 4 ) and Warnings and Precautions ( 5.1 ) ]. If metformin-associated lactic acidosis is suspected, immediately discontinue glyburide and metformin hydrochloride and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [ see Warnings and Precautions ( 5.1 ) ]. See full prescribing information for complete boxed warning. • Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms include malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL. ( 5

Contraindications

4 CONTRAINDICATIONS Glyburide and metformin hydrochloride tablets is contraindicated in patients with: • Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [ see Warnings and Precautions ( 5.1 ) ]. • Hypersensitivity to metformin or glyburide. • Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. • Concomitant administration of bosentan [ see Drug Interactions ( ) ]. • Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) (, 5.1 ) • Hypersensitivity to metformin or glyburide. () • Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. () • Concomitant administration of bosentan. (, )