Special instructions and precautions
Risk of developing lactic acidosis
Metformin can cause a rare but very serious complication, lactic acidosis, especially if kidney function is impaired. The risk of developing lactic acidosis increases in the case of uncontrolled diabetes, serious infections, prolonged fasting, alcoholism, dehydration (see information below), liver failure and any pathology in which hypoxia occurs (for example, severe heart disease).
If you have any of these conditions, talk to your doctor before using metformin.
Stop taking metformin for a short time if you have a risk of dehydration (more body fluid loss than necessary), such as severe vomiting, diarrhea, fever, exposure to high temperatures, or insufficient fluid intake.
If you have any questions, consult your doctor,
If you develop symptoms of lactic acidosis, stop taking metformin and tell your doctor or go to your nearest hospital immediately, as lactic acidosis can lead to coma.
Symptoms of lactic acidosis:
- vomit
- abdominal pain
- muscle spasms
- general poor health, accompanied by severe fatigue
- labored breathing
- decreased body temperature and heart rate
Lactic acidosis requires emergency medical attention.
If you are having major surgery, you should stop taking metformin for the duration of surgery and for some time afterward.
Your doctor will advise you when to stop and restart treatment.
Metformin as monotherapy does not cause hypoglycemia (lowering blood glucose levels). However, when used simultaneously with other antidiabetic drugs (sulfonylurates, insulin, meglitinides), there is a risk of developing hypoglycemia.
If you experience symptoms of hypoglycemia, such as weakness, dizziness, increased sweating, rapid heartbeat, or problems with vision or concentration, you should immediately drink or eat something containing sugar.
Renal function should be closely monitored at least once a year during treatment with metformin, or more often if you are elderly or have worsening kidney function.
Drug interactions
If you need to have intravascular injection of iodinated contrast agents, such as for x-rays, you must stop taking metformin before or during the procedure. Your doctor will tell you when to stop or when to restart taking metformin.
Tell your doctor if you are taking, have recently taken or might take any other medicines. You may need to have your blood glucose levels and kidney function assessed more frequently, or your doctor may need to adjust your metformin dose.
It is especially important to note the following medications:
- medications that increase urine production (diuretics).
- medications that have analgesic and anti-inflammatory effects (NSAIDs and COX-2 inhibitors such as ibuprofen and celecoxib).
- certain medications to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).
- beta-2 adrenergic agonists such as salbutamol or terbutaline (drugs used to treat asthma).
- corticosteroids (used to treat various conditions such as severe skin inflammation or asthma).
- Medicines that may affect blood levels of metformin, especially if kidney function is impaired (eg, verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).
- other medicines used to treat diabetes mellitus
Metformin and alcohol
Avoid excessive drinking of alcohol while taking metformin as this may cause lactic acidosis (see Warnings and Precautions).
Pregnancy and breastfeeding
During pregnancy, you need insulin to treat diabetes.
Check with your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant before taking this drug as it may change your treatment.
It is not recommended to take metformin while breastfeeding.
Metformin Canon tablets 1000 mg 30 pcs.
Contraindicated combinations. Radiological studies using iodine-containing X-ray contrast agents can cause the development of lactic acidosis in patients with diabetes mellitus against the background of functional renal failure. The use of metformin should be discontinued 48 hours before and not resumed until 48 hours after an X-ray examination using radiocontrast agents. Combinations not recommended. With the simultaneous use of metformin with alcohol and ethanol-containing drugs, during acute alcohol intoxication, during fasting or following a low-calorie diet, as well as in liver failure, the risk of developing lactic acidosis increases. Combinations requiring special care. When metformin is used simultaneously with danazol, a hyperglycemic effect may develop. If treatment with danazol is necessary and after stopping its use, a dose adjustment of metformin is required under the control of blood glucose concentrations. Chlorpromazine in high doses (100 mg/day) reduces insulin release and increases blood glucose concentrations. When used simultaneously with antipsychotics and after stopping their use, a dose adjustment of metformin is required under the control of blood glucose concentrations. Glucocorticosteroids (GCS), when administered parenterally and locally, reduce glucose tolerance and increase blood glucose concentrations, in some cases causing ketosis. If it is necessary to use such a combination and after stopping the use of corticosteroids, a dose adjustment of metformin is required under the control of blood glucose concentrations. With the simultaneous use of loop diuretics and metformin, there is a risk of developing lactic acidosis due to the possible occurrence of functional renal failure. The use of beta2-adrenergic agonists by injection reduces the hypoglycemic effect of metformin due to stimulation of beta2-adrenergic receptors. In this case, you should monitor the concentration of glucose in the blood and, if necessary, use insulin. Angiotensin-converting enzyme inhibitors and other antihypertensive drugs may decrease blood glucose concentrations. If necessary, the dose of metformin should be adjusted. With simultaneous use of metformin with sulfonylurea derivatives, insulin, acarbose and salicylates, the hypoglycemic effect may be enhanced. Nifedipine increases the absorption and Cmax of metformin, which must be taken into account when using them simultaneously. Loop diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of decreased kidney function. In this case, caution must be exercised when using metformin.
Metformin
Lactic acidosis
Lactic acidosis is a rare but serious (high mortality unless promptly treated) complication, most often occurring in the setting of acute deterioration of renal function, cardiopulmonary disease or sepsis. Accumulation of metformin against the background of acute deterioration of renal function increases the risk of lactic acidosis.
If dehydration occurs (severe diarrhea or vomiting, fever or decreased fluid intake), you should temporarily stop treatment with metformin and consult a doctor.
Treatment of patients taking metformin with drugs that can acutely worsen renal function (such as antihypertensive drugs, diuretics or NSAIDs) should be initiated with caution.
Other associated risk factors for lactic acidosis should be considered, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure and any other condition associated with severe hypoxia, as well as concomitant use with drugs that can lead to lactic acidosis (see. sections “Contraindications” and “Interaction with other drugs”). This may help reduce the incidence of lactic acidosis.
Patients and/or caregivers should be informed of the risk of lactic acidosis.
Lactic acidosis is characterized by acidotic shortness of breath, abdominal pain, muscle cramps, severe asthenia and hypothermia followed by coma. If suspicious symptoms occur, the patient should stop taking metformin and seek immediate medical attention.
Diagnostic laboratory parameters are a decrease in blood pH (less than 7.35), lactate content in the blood plasma over 5 mmol/l, increased anion gap and lactate/pyruvate ratio.
Doctors should warn patients about the risk of developing and symptoms of lactic acidosis.
Administration of iodinated contrast agents
Intravascular administration of iodinated contrast agents can lead to nephropathy and accumulation of metformin, which increases the risk of developing lactic acidosis. The use of metformin should be stopped 48 hours before such a procedure and resumed no earlier than 48 hours after it, provided that the examination did not reveal renal dysfunction (see section “Interaction with other drugs”).
Surgical operations
The use of metformin should be discontinued 48 hours before elective surgery under general, spinal or epidural anesthesia and can be continued no earlier than 48 hours after surgery, provided that the examination did not reveal impaired renal function.
Kidney function
Since metformin is excreted by the kidneys, it is necessary to determine CC before starting treatment and regularly thereafter:
- at least once a year in patients with normal renal function;
- every 3-6 months in patients with CC 45-59 ml/min and every 3 months with CC 30-44 ml/min.
When CC is less than 30 ml/min, the use of metformin is contraindicated. Treatment with metformin should be suspended in the presence of conditions that may affect renal function.
Particular caution should be exercised in case of possible impairment of renal function in elderly patients (due to the asymptomatic nature), with simultaneous use of antihypertensive drugs, diuretics or NSAIDs.
Heart failure
Patients with heart failure have a higher risk of developing hypoxia and renal failure. Patients with chronic heart failure should have cardiac and renal function monitored regularly while taking metformin.
Taking metformin in heart failure with unstable hemodynamic parameters is contraindicated.
Children and teenagers
The diagnosis of type 2 diabetes mellitus must be confirmed before starting treatment with metformin.
In clinical studies lasting 1 year, metformin was shown to have no effect on growth and puberty. However, due to the lack of long-term data, careful monitoring of the subsequent effects of metformin on these parameters in children, especially during puberty, is recommended. Clinical experience with metformin in children aged 10 to 12 years is limited, so the most careful monitoring is necessary in children in this age group.
Other Precautions
- Patients are advised to continue to follow a diet with even carbohydrate intake throughout the day. Overweight patients are recommended to continue to follow a hypocaloric diet (but not less than 1000 kcal/day).
— Patients should inform the doctor about any treatment being carried out and any infectious diseases.
— It is recommended that routine laboratory tests be performed regularly to monitor diabetes mellitus.
— Metformin in monotherapy does not cause hypoglycemia, however, it is recommended to exercise caution when using it in combination with insulin or other hypoglycemic agents (for example, sulfonylurea derivatives, repaglinide, etc.).
The use of metformin is recommended for the prevention of type 2 diabetes mellitus in persons with prediabetes and additional risk factors for the development of overt type 2 diabetes mellitus, such as:
- age less than 60 years;
- body mass index (BMI) > 30 kg/m2;
- history of gestational diabetes mellitus;
- family history of diabetes in first-degree relatives;
- increased concentration of triglycerides;
- reduced concentration of HDL cholesterol;
- arterial hypertension.
Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, rapid heartbeat, blurred vision, or difficulty concentrating.
Metformin did not affect fertility in male or female rats when administered at doses three times the maximum recommended daily dose for humans.
