Metfor XR Special Precautions

Lactic acidosis: 500 mg: Lactic acidosis, an uncommon but significant metabolic consequence, most commonly arises during an acute worsening of renal function, cardiorespiratory disease, or sepsis. Metformin accumulation develops with acute renal function deterioration and increases the risk of lactic acidosis.
Metformin should be temporarily discontinued in the event of dehydration (severe diarrhea or vomiting, fever, or decreased fluid intake), and consultation with a healthcare provider is advised. Antihypertensives, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) should be used with caution in metformin-treated individuals. Excessive alcohol consumption, hepatic insufficiency, poorly controlled diabetes, ketosis, prolonged fasting, and any conditions linked with hypoxia, as well as concurrent use of medical medications that may cause lactic acidosis, are all risk factors for lactic acidosis.
Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is distinguished by acidotic dyspnea, stomach pain, muscle cramps, asthenia, hypothermia, and coma. If symptoms are suspected, the patient should discontinue metformin and seek emergency medical assistance. Reduced blood pH (7.35), elevated plasma lactate levels (>5 mmol/L), and an increased anion gap and lactate/pyruvate ratio are all diagnostic laboratory findings.
750 mg: Lactic acidosis is a very rare, but serious (high mortality in the absence of prompt treatment), metabolic complication. Risk factors include poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, severe infection, hepatic insufficiency, and any condition associated with hypoxia (such as decompensated cardiac failure, acute myocardial infarction) or the concomitant use of medications which might cause lactic acidosis (such as NRTIs) (see also Contraindications).
Lactic acidosis can occur due to metformin accumulation. Reported cases of lactic acidosis in patients treated with metformin have occurred primarily in diabetic patients with acute renal failure or acute worsening of renal function.
Special caution should therefore be paid to situations where renal function may become acutely impaired (see also Contraindications). For example in case of dehydration (severe or prolonged diarrhea or vomiting) or when initiating drugs which can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs).
In the acute conditions listed, metformin must be immediately and temporarily discontinued.
The following non-specific symptoms could be signs of lactic acidosis: such as muscle cramps, digestive disorders as abdominal pain and severe asthenia.
Diagnosis: Lactic acidosis is characterized by acidotic dyspnea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH (below 7.35), plasma lactate levels above 5 mmol/L, and an increased anion gap and lactate/pyruvate ratio. In case of lactic acidosis, the patient should be immediately hospitalized (see also Overdosage).
Physicians must alert the patients on the risk and on the symptoms of lactic acidosis. Patients should be instructed to immediately seek medical attention and to stop taking metformin. Metformin must be immediately discontinued, at least temporarily, until the situation is clarified. Reintroduction of metformin should then be discussed taking into account the benefit/risk ratio on an individual basis as well as renal function.
Renal function: 500 mg: GFR should be measured before starting treatment and then on a frequent basis. Metformin is contraindicated in patients with GFR less than 30 mL/min and should be discontinued temporarily in the presence of diseases that impair renal function.
750 mg: As metformin is excreted by the kidney, it is recommended that CrCl (this can be estimated from serum creatinine levels by using the Cockcroft-Gault formula) or eGFR should be determined before initiating treatment and regularly thereafter: At least annually in patients with normal renal function.
At least every 3 to 6 months in patients with CrCl between 45 and 59 mL/min or eGFR between 45 and 59 mL/min/1.73 m² and in elderly subjects.
At least every 3 months in patients with CrCl between 30 and 44 mL/min or eGFR between 30 and 44 mL/min/1.73 m².
In case CrCl is below 30 mL/min or eGFR is below 30 mL/min/1.73 m² respectively, metformin is contraindicated (see Contraindications). Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution is needed in situations where renal function may become acutely impaired, for example due to dehydration (severe or prolonged diarrhea or vomiting), or when initiating drugs which can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs). In the acute conditions listed, metformin must be immediately and temporarily discontinued. In these cases, it is also recommended to check renal function before initiating treatment with metformin.
Cardiac function: Hypoxia and renal insufficiency are more common in patients with heart failure. Metformin may be administered in patients with stable chronic heart failure with regular monitoring of cardiac and renal function. Metformin is not recommended for persons with acute or unstable heart failure.
Administration of iodinated contrast agents: 500 mg: Intravenous injection of iodinated contrast agents may result in contrast induced nephropathy, which can lead to metformin buildup and an increased risk of lactic acidosis. Metformin should be stopped before to or during the imaging process and not resumed for at least 48 hours, assuming renal function has been re-evaluated and determined to be stable.
Surgery: 500 mg: Metformin must be stopped before undergoing surgery under general, spinal, or epidural anesthesia. Therapy should be continued no sooner than 48 hours after surgery or the commencement of oral nourishment, and only after renal function has been re-evaluated and proven to be stable.
Other precautions: All patients should follow their diet with a regular carbohydrate distribution throughout the day. Patients who are overweight should maintain their energy-restricted diet.
The standard laboratory tests for diabetes monitoring should be done on a regular basis.
Metformin alone does not cause hypoglycemia; however, it should be used with caution when combined with insulin or other oral antidiabetics (e.g., sulphonylureas or meglitinides).
Tablet shells may be found in the feces. Patients should be informed that this is common.
500 mg: Metformin may lower serum vitamin B12 levels. Low vitamin B12 levels become more likely with increased metformin dose, therapy duration, and/or in patients with risk factors for vitamin B12 insufficiency. Vitamin B12 serum levels should be examined if there is a suspicion of vitamin B12 insufficiency (such as anemia or neuropathy).
Patients with risk factors for vitamin B12 insufficiency may require periodic vitamin B12 monitoring. Metformin therapy should be continued for as long as it is tolerated and not contraindicated, and appropriate vitamin B12 deficiency treatment should be offered in accordance with current clinical standards.
Effects on Ability to Drive and Use Machines: Since metformin monotherapy does not result in hypoglycemia, it has no impact on the capacity to operate machinery or operate a vehicle.
However, when metformin is combined with other anti-diabetic medications (such as sulphonylureas, insulin, or meglitinides), patients should be informed of the possibility of hypoglycemia.
Use in the Elderly: 500 mg: Due to the insufficient data on therapeutic efficacy in the risk reduction or delayed onset of type 2 diabetes in patients 75 years and older, introduction of metformin is not advisable in these patients.