Glucophage Special Precautions

Lactic Acidosis: Lactic acidosis is a rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin hydrochloride accumulation. Reported cases of lactic acidosis in patients on metformin hydrochloride have occurred primarily in diabetic patients with significant renal failure. It is possible and recommended that the incidence of lactic acidosis be reduced by assessing also other associated risk factors eg, poorly-controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.
Diagnosis: The risk of lactic acidosis must be considered in the event of nonspecific signs eg, muscle cramps with digestive disorders as abdominal pain and severe asthenia.
Lactic acidosis is characterised by acidotic dyspnea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH (<7.25), plasma lactate levels (>5 mmol/L), and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, metformin hydrochloride should be discontinued and the patient should be hospitalized immediately.
Renal Function: As metformin hydrochloride is excreted by the kidney, it is recommended that creatinine clearance (CrCl) levels be determined before initiating treatment and regularly thereafter: At least annually in patients with normal renal function and at least 2-4 times a year in patients with CrCl at the lower limit of normal and in elderly subjects.
Decreased renal function in elderly subjects is frequent and symptomatic. Special caution is recommended in situations where renal function may become impaired eg, when initiating antihypertensive therapy or diuretic therapy, and when starting therapy with a nonsteroidal anti-inflammatory drug (NSAID).
Administration of Iodinated Contrast Agent: Intravascular administration of iodinated contrast materials in radiologic studies can lead to renal failure. This may induce metformin metformin accumulation and may expose to lactic acidosis. Therefore, depending on the renal function, metformin must be discontinued 48 hrs before the test or from the time of the test and may not be reinstituted until 48 hrs afterwards, and only after renal function has been re-evaluated and found to be normal.
Surgery: Metformin hydrochloride must be discontinued 48 hrs before elective major surgical interventions and may not be reinstituted until 48 hrs afterwards, and only after renal function has been reevaluated and found to be normal.
Other Precautions: It is recommended that all patients continue their diet with a regular distribution of carbohydrate intake during the day and that overweight patients should continue their energy-restricted diet.
It is recommended that the usual laboratory tests for diabetes monitoring be performed regularly.
Metformin hydrochloride alone does not cause hypoglycaemia, but caution is advised when it is used in combination with insulin or sulfonylureas.
Effects on Ability to Drive or Operate Machinery: Metformin hydrochloride monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines. However, patients should be alerted to the risk of hypoglycemia when metformin hydrochloride is used in combination with other antidiabetic agents (sulfonylureas, insulin, meglitinides).
Use in pregnancy & lactation: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with increased congenital abnormalities and perinatal mortality. A limited amount of data from the use of metformin in pregnant women does not indicate an increased risk of congenital abnormalities. Animal studies do not indicate harmful effects with respect to pregnancy, embryonic or fetal development, parturition or postnatal development.
However, when the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin, but insulin be used to maintain blood glucose levels as close to normal as possible.
Metformin is excreted into milk in lactating rats and human breast milk. No adverse effects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breastfeeding. Should be made, taking into account the benefit of breastfeeding and the potential risk of adverse effects on the child.
Use in children: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin hydrochloride is initiated. No effect of metformin hydrochloride on growth and puberty has been detected during controlled clinical studies of 1 year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin hydrochloride on these parameters in metformin hydrochloride treated children, especially pre-pubescent children, is recommended.
Children between 10 and 12 years: Only 15 subjects between 10 and 12 years were included in the controlled clinical studies conducted in children and adolescents. Although efficacy and safety of metformin hydrochloride in older children and adolescents, particular caution is recommended when prescribing to children between 10 and 12 years.