Renal function metformin

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

The drug is used cautiously during surgery. Metformin use is temporarily discontinued for surgical procedures. The drug therapy is restarted when the patient s oral intake has been resumed and renal function is normal. 

Diabetes pretransplant Insulin Oral hypoglycemics Metformin Glucocorticoids, TAC, and CSA also increase hypoglycemic requirements insulin requirements will increase with improving renal function Avoid in those with Rl... 

Metformin (Y) Glucophage 500, 850, 1,000 500 mg twice a day Assess renal function... 

Metformin is a biguanide used to treat diabetes mellitus. It is contraindicated in patients undergoing general anaesthesia since anaesthesia can interfere with renal function. The risk of lactic acidosis associated with metformin increases in patients with renal impairment. Metformin should be stopped before and during surgery where anaesthesia is indicated. Metformin should only be restarted after the renal function has returned to normal. 

Special patient populations Initial and maintenance dosing should be conservative in patients with advanced age because of the potential for decreased renal function. Base any dosage adjustment on a careful assessment of renal function. Generally, do not titrate elderly, debilitated, or malnourished patients to the maximum dose. Do not initiate metformin IR and ER treatment in patients 80 years of age and older unless measurement of Ccr demonstrates that renal function is not reduced. 

Renal function impairment Metformin is known to be excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Do not give metformin to patients with serum creatinine levels above the upper limit of normal for their age. 

Eideriy Because aging is associated with reduced renal function, use metformin with caution as age increases. Generally, do not titrate elderly patients to the maximum dose of metformin (see Administration and Dosage). 

Hypoxic states Cardiovascular collapse (shock), acute CHF, acute Ml, and other conditions characterized by hypoxemia have been associated with lactic acidosis and may cause prerenal azotemia. If such events occur, discontinue metformin. Surgicai procedures Temporarily suspend metformin for surgical procedures (unless minor and not associated with restricted intake of food and fluids). Do not restart until the patient s oral intake has resumed and renal function is normal. 

Special Precaution Renal function should be monitored to minimize risk of metformin accumulation... 

To this one could add that drugs that compromise renal function should not be combined with metformin. 

An 82-year-old man and a 76-year-old man with normal renal function developed increased lactate concentrations (3.6 mmol/1 and 3.2 mmol/1 respectively) a few weeks after starting to take metformin (54). Both had a low bicarbonate concentration and high anion gap. The second patient was also taking ciprofloxacin for a urinary tract infection. In both patients lactate reached normal values after metformin was withdrawn. 

Five patients with metformin-associated severe lactic acidosis, seen between 1 September 1998 and 31 May 2001, have been reported (58). Two had attempted suicide. All had severe metabolic acidosis with a high anion gap and raised blood lactate concentrations. Four developed profound hypotension and three had acute respiratory failure. Three had normal preceding renal function. Three required conventional hemodialysis and two continuous renal replacement therapy. 

Metformin is increasingly being used in the polycystic ovarian syndrome and therefore in lactating women. In seven breastfeeding mothers taking a median dose of 1500 mg/day, the mean relative infant dose transferred in the milk was 0.28% (120). Serum metformin concentrations were very low or undetectable in infants and they appeared to be healthy. A specific warning was given for children with impaired renal function (prematurity, renal insufficiency). 

When to stop metformin in people with diabetes mellitus and abnormal renal function continues to be debated. It has been suggested that it should not be used in those with an eGFR (MDRD) of less than 60 ml/minute (122). However, this would exclude many people who have been taking metformin for many years without apparent ill effect. Others have recommended using the Cockcroft-Gault equation (SEDA-29, 527), which is preferable. 

Since January 1998 the package insert approved by the FDA has stated Glucophage (metformin) should be discontinued at the time of or prior to the procedure and withheld for 48 hours subsequent to the procedure and reinstituted only after renal function has been reevaluated and found to be normal (142). 

A 59-year-old obese woman with normal renal function, taking metformin 500 mg tds, took orlistat 120 mg tds for 3 months (147). She developed abdominal pain and diarrhea, for which she was given cimetidine, and became weak and dizzy, with blurred vision, reduced consciousness, agitation, and confusion. Her pH was 6.5, bicarbonate 2 mmol/1, base deficit 38 mmol/1, and lactate 21 mmol/1. She required rehydration, bicarbonate, inotropic support and renal replacement therapy. 

The authors suggested that chronic diarrhea induced by orlistat could have led to impaired renal function or that orlistat could have increased the absorption of metformin by reducing fat absorption. 

Lalau JD, Race JM, Brinquin L. Lactic acidosis in metformin therapy. Relationship between plasma metformin concentration and renal function. Diabetes Care 1998 21(8) 1366-7. 

These include mesalazine, metformin, NSAIDs, tetracyclines (except doxycycline and minocycline), chloramphenicol, lithium, methotrexate, chloroquine, fibrates, chlorpropamide and glibenclamide, Clinically, it is useful to measure urine output per hour or per 24 hours as a fall in urine output in the presence of adequate fluid intake often indicates or warns of some impairment of renal function. Furthermore, it is neither expensive nor time-consuming to perform a quick test for albumin, casts and red cells in the urine, and to measure pH. Creatinine clearance values are often used to determine the safe doses for several drugs (e.g. NSAIDs, ciclosporin). 

The use of contrast media in patients taking metformin should be carried out cautiously. Contrast-induced nephropathy can lead to retention of metformin and lactic acidosis. However, there is no conclusive evidence that intravascular contrast agents precipitate metformin-induced lactic acidosis in patients with normal serum creatinine concentrations (under 130 pmol/1). This complication was almost always observed in non-insulin dependent diabetic patients with abnormal renal function before injection of contrast media (4,316). 

Lactic acidosis can occur after the use of intravascular iodinated contrast agents in patients taking metformin. Metformin is excreted by the kidneys, and renal insufficiency can lead to its retention, which can cause fatal lactic acidosis. The manufacturers have recommended that metformin should be withdrawn for 48 hours before and 48 hours after the administration of intravascular contrast media, which can cause renal damage, and treatment should not be restarted until normal renal function is confirmed. Reviews of reported cases of lactic acidosis after contrast administration have shown that there was pre-existing renal impairment in all cases. A retrospective evaluation of patients taking metformin who underwent... 

---