Black Box Warnings .
can occur due to metformin accumulation; rare (approx 0.03 cases/1000 pt-yr) but fatal in 50% of cases; most cases in diabetics w/ significant renal impairment, often w/ multiple concomitant medical/surgical problems and meds; incr. risk if sepsis, dehydration, excess alcohol intake, hepatic insufficiency, renal impairment, >80 yo, or acute/unstable CHF; risk incr. w/ degree of renal impairment and age; risk may decr. w/ renal fxn monitoring and minimum effective dose; onset may be subtle w/ nonspecific sx incl. malaise, myalgias, resp. distress, incr. somnolence, nonspecific abdominal distress; lab findings incl. low pH, incr. anion gap, incr. blood lactate; GI sx occurring after tx stable not likely drug-related, may indicate lactic acidosis or other serious dz; suspect lactic acidosis in diabetic pt w/ metabolic acidosis w/o ketoacidosis; measure CrCl before and during tx; temporarily D/C metformin if hypoxemia, dehydration, sepsis or prior to intravascular radiocontrast study or any surgery; avoid in hepatic dz; avoid excessive acute or chronic alcohol intake; D/C metformin immed. if lactic acidosis suspected, hospitalize pt and monitor serum electrolytes, ketones, blood glucose, blood pH, lactate levels, and metformin levels (if indicated), use prompt HD to correct acidosis and remove accumulated metformin