See Supplemental Patient Information
- Accumulation of metformin may cause a rare but fatal complication called lactic acidosis. Patients with sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute CHF are at a greater risk for developing lactic acidosis. Regular monitoring of renal function in patients receiving therapy and use of minimum effective dose of metformin/repaglinide therapy may significantly reduce this risk [US Black Box Warning]
- Lactic acidosis is manifested by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and abdominal distress. Lab abnormalities include low pH, increased anion gap, and elevated blood lactate levels (>5 mmol/L) [US Black Box Warning]
- Hypothermia, hypotension, and resistant bradyarrhythmias may occur in case of severe acidosis. Patients and physicians must remain alert to symptoms of lactic acidosis
- Fasting venous plasma lactate levels above the upper limit of normal but <5 mmol/L in patients receiving therapy do not necessarily signify impending lactic acidosis, and may occur as a result of poorly controlled diabetes /obesity, vigorous physical activity, or technical issues in sample handling
- Suspect lactic acidosis in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis
- In case of suspected lactic acidosis, discontinue therapy and promptly hospitalize the patient. Prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin, resulting in reversal of symptoms and recovery
- Renal impairment increases the risk of metformin accumulation, thereby increasing the risk of lactic acidosis. Therapy is therefore contraindicated in patients with renal impairment
- Assess renal function prior to starting therapy and annually thereafter to exclude the possibility of impaired renal function
- Radiologic studies with intravascular iodinated contrast media may lead to acute alteration of renal function and may cause lactic acidosis in patients receiving metformin/repaglinide therapy
- Therapy must be temporarily discontinued at the time of or prior to the intravascular contrast studies with iodinated contrast media, and withheld for 48 hrs subsequent to the procedure and re-instituted only after evaluation of renal function has been found to be normal
- Treatment with metformin/repaglinide may cause hepatic impairment. Avoid use in patients with hepatic dysfunction
- Alcohol may augment the effect of metformin on lactate metabolism. Caution patients against excessive intake of alcohol during therapy
- Avoid use in combination with NPH-insulin, as repaglinide and NPH-insulin combination increases the risk of myocardial ischemia
- Repaglinide may cause severe hypoglycemia; start therapy with lowest available repaglinide component of the combination drug in patients who have not been treated previously with a meglitinide
- Elderly, alcoholic, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency are at a greater risk of hypoglycemia
- Metformin may cause reductions in vitamin B12 levels, which is rarely associated with anemia and may be reversed by discontinuation of therapy or vitamin B12 supplementation. Monitor hematologic parameters and vitamin B12 levels regularly during therapy
- Temporarily discontinue metformin/repaglinide therapy during conditions like fever, trauma, infection, or surgery which may cause a temporary loss of glycemic control. Therapy may be restarted after the acute condition resolves
- Temporarily discontinue metformin/repaglinide therapy prior to major surgical procedures; therapy may be restarted after the patient has resumed oral intake and renal function has been evaluated as normal
- Exercise caution when using metformin/repaglinide concomitantly with drugs that may affect renal function, or result in marked hemodynamic change or may interfere with metformin disposition, such as cationic drugs excreted by renal tubular secretion
- Cardiovascular collapse, acute CHF, acute MI, and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. Discontinue therapy if any such symptoms occur
- Type 2 diabetic patients previously stabilized on metformin/repaglinide therapy showing laboratory/clinical abnormalities must be evaluated for evidence of ketoacidosis or lactic acidosis. Monitor serum electrolytes, ketones, blood glucose, blood pH, lactate, pyruvate, and metformin levels in such patients
Cautions: Use cautiously in
- Insulin use
- May induce ovulation
Supplemental Patient Information
- Advise patients to remain alert to signs and symptoms of lactic acidosis and promptly notify any unexplained symptoms to their physician
- Educate patients about the importance of adherence to dietary instructions, regular exercise program, regular monitoring of blood glucose, HbA1c, renal function and hematologic parameters
- Caution patients against excessive alcohol intake, either acute or chronic, while receiving metformin/repaglinide therapy
Pregnancy Category:C
Breastfeeding: Low levels of metformin are detectable in serum of breastfed infants. Metformin levels in milk are relatively constant during maternal metformin use and infants receive <0.5% of the maternal weight-adjusted dosage. Use cautiously when nursing newborn/premature infants and those with renal impairment. Due to lack of data available regarding the use of repaglinide during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn/preterm infant. Monitoring blood glucose levels of the breastfed infant is recommended during maternal treatment with repaglinide. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 18 Aug 2011). Manufacturer recommends avoiding use of this combination drug in nursing mothers due to the risk of hypoglycemia in breastfed infants.
US Trade Name(s)
US Availability
PrandiMet (metformin/repaglinide)
Canadian Trade Name(s)
Canadian Availability
UK Trade Name(s)
UK Availability
Australian Trade Name(s)
Australian Availability
[Outline]
Drug Name: PrandiMet 1/500 Oral Tablet
Ingredient(s): Metformin mixture with repaglinide
Imprint: 1mg;500mg
Color(s): Yellow
Shape: Round
Size (mm): 5.00
Score: 2
Inactive Ingredient(s): cellulose, microcrystalline / hypromellose / iron / magnesium stearate / meglumine / polacrilin potassium / poloxamer 188 / polyethylene glycol / povidone / sorbitol / talc / titanium dioxide
Drug Label Author:
Novo Nordisk
DEA Schedule:
Non-Scheduled
Drug Name: PrandiMet 2/500 Oral Tablet
Ingredient(s): Metformin mixture with repaglinide
Imprint: 2mg;500mg
Color(s): Pink
Shape: Round
Size (mm): 5.00
Score: 2
Inactive Ingredient(s): cellulose, microcrystalline / hypromellose / iron / magnesium stearate / meglumine / polacrilin potassium / poloxamer 188 / polyethylene glycol / povidone / propylene glycol / sorbitol / talc / titanium dioxide
Drug Label Author:
Novo Nordisk
DEA Schedule:
Non-Scheduled
