Metformin administration

Lactic acidosis (buildup of lactic acid in the blood) may also occur with die administration of metformin. Although lactic acidosis is a rare adverse reaction, its occurrence is serious and can be fatal. Lactic acidosis occurs mainly in patients with kidney dysfunction. Symptoms of lactic acidosis include malaise (vague feeling of bodily discomfort), abdominal pain, rapid respirations, shortness of breath, and muscular pain. In some patients vitamin B12 levels are decreased. This can be reversed with vitamin B12 supplements or with discontinuation of the drug therapy. Because... 

Metformin is the only Food and Drug Administration (FDA) approved oral diabetic agent in children (greater than or equal to age 10) other oral agents... 

The only biguanide approved by the Food and Drug Administration (FDA) and currently available in the United States is metformin. Metformin was approved in the United States in 1995, although it has been used extensively in Canada and Europe since 1959. This agent is thought to lower blood... 

Sitagliptin is a dipeptidylpeptidase-4 inhibitor that increases insulin secretion and lowers glucagon secretion. Sitagliptin is available for oral administration. It is indicated in patients with type 2 diabetes mellitus in combination with either metformin (biguanide) or a sulphonylurea or a thiazolidinedione. 

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). 

Renal impairment - Metformin is contraindicated in patients with renal impairment. Therefore, concomitant administration of rosiglitazone and metformin is contraindicated in these patients. However, no dosage adjustment is necessary when rosiglitazone is used as monotherapy in patients with renal impairment. 

Pramlintide is approved for concurrent mealtime administration in individuals with type 2 diabetes treated with insulin, metformin, or a sulfonylurea who are unable to achieve their postprandial glucose targets. Combination therapy results in a significant reduction in early postprandial glucose excursions mealtime insulin or sulfonylurea doses usually have to be reduced to prevent hypoglycemia. 

Pentikainen PJ, Neuvonen PJ, Penttila A. Pharmacokinetics of metformin after intravenous and oral administration to man. Em J Clin Pharmacol 1979 16(3) 195-202. 

Discontinue nephrotoxic drugs—Nonsteroidal antiinflammatory drugs and diuretics should be withheld for at least 24 hours before and after exposure to contrast medium, if possible. Metformin should be withheld for 48 hours before the administration of CM and until it is certain that CIN has not occurred. 

AMILORIDE METFORMIN T metformin levels and risk of lactic acidosis Metformin is not metabolized in humans and is not protein-bound. Competition for renal tubular excretion is the basis for t activity or retention of metformin Theoretical possibility. Requires reduction of metformin dose to be considered, or the avoidance of co-administration... 

METFORMIN ANTIHISTAMINES-KETOTIFEN 1 platelet count Unknown Avoid co-administration (manufacturers recommendation)... 

METFORMIN H2 RECEPTOR BLOCKERS -CIMETIDINE, RANITIDINE t level of metformin and risk of lactic acidosis. The onset of lactic acidosis is often subtle with symptoms of malaise, myalgia, respiratory distress and t nonspecific abdominal distress. There may be hypothermia and resistant bradyarrhythmias Metformin is not metabolized in humans and is not protein-bound. Competition for renal tubular excretion is the basis for T activity or retention of metformin. Cimetidine competes for the excretory pathway A theoretical possibility. Need to consider l dose of metformin or avoidance of co-administration. Warn patients about hypoglycaemia - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

Fig. 6 Plasma metformin concentrations following the administration of metformin (450mg/kg) as PO bolus, duodenal infusion, and gastroretentive CR tablets (CR I or CR II) to streptozotocin-diabetic rats. (From Ref...

Hoffman, A. Stepensky, D. Pharmacodynamic aspects of modes of drug administration for optimization of drug therapy. Crit. Rev. Ther. Drug Carrier Syst. 1999,16, 571-639. Stepensky, D. Friedman, M. Srour, W. Raz, I. Hoffman, A. Preclinical evaluation of pharmacokinetic-pharmacodynamic rationale for oral CR metformin formulation. J. Contr. Release. 2001, 71, 107-115. 

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... 

The administration of metformin at bedtime instead of supper time may improve diabetes control by reducing morning hyperglycaemia (Ravina and Minuchin, 1990). Metformin was not distinguished from tolbutamide in elderly diabetic patients, except in that it was associated with weight loss (Josephkutty and Potter, 1990). 

Intravenous administration of 7-ketocholesterol decreased the uptake of cholesterol into rabbit aorta.75 5a-Cholest-8(14)-en-38-ol-15-one suppressed serum cholesterol levels and hepatic cholesterol synthesis. 6 S-8527 significantly reduced serum cholesterol by inhibiting the hepatic synthesis of lipoprotein fractions carrying cholesterol.77 Metformin produced only a slight reduction of plasma cholesterol levels in rabbits fed a high cholesterol diet. However, it markedly decreased aortic cholesterol esters and the atheromatous process, with a simultaneous change in the composition of VLDL.78 79... 

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