Instructions for use Metformin Sandoz film-coated tablets 850 mg blister No. 120
Composition
active ingredient: metformin;
1 tablet contains metformin hydrochloride 500 mg or 850 mg;
excipients: povidone, magnesium stearate;
film coating: hypromellose, titanium dioxide (E 171), macrogol 4000.
Dosage form
Film-coated tablets.
Main physicochemical properties:
500 mg tablets: round, white, biconvex, film-coated tablets, embossed with “M 500” on one side and plain on the other side;
850 mg tablets: oval white film-coated tablets, embossed with “M 850” on one side and a score line on the other side.
Pharmacotherapeutic group
Oral hypoglycemic agents, except insulins. Biguanides. ATC code A10B A02.
Pharmacological properties
Pharmacodynamics
Metformin is a biguanide with antihyperglycemic effect. It reduces both the initial and postprandial glucose levels in the blood plasma. It does not stimulate insulin secretion and does not cause a hypoglycemic effect.
Metformin works in three ways:
– leads to a decrease in glucose production in the liver due to inhibition of gluconeogenesis and glycogenolysis;
– improves insulin sensitivity in muscles by improving peripheral glucose uptake and utilization;
– delays the absorption of glucose in the intestine.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthetase. Increases the transport capacity of all types of membrane glucose transporters (GLUT).
During the use of metformin, the body weight of patients remained stable or moderately decreased. In addition to its effect on glycemia, metformin has a beneficial effect on lipid metabolism. When taking the drug in therapeutic doses, it was noted that metformin reduces the levels of total cholesterol, low-density lipoproteins and triglycerides.
Pharmacokinetics
Absorption. After oral administration, metformin is almost completely absorbed from the gastrointestinal tract, 20-30% is excreted in the feces. The time to reach maximum concentration (Tmax) is 2.5 hours. Absolute bioavailability is approximately 50-60%.
When taken with food, the absorption of metformin is reduced and slightly delayed.
Distribution. Binding to plasma proteins is negligible. Metformin penetrates into erythrocytes. The maximum concentration in the blood is lower than in plasma and is reached after approximately the same time. Erythrocytes most likely represent a second distribution chamber. The mean volume of distribution (Vd) ranges from 63 to 276 l.
Metabolism: Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination: Renal clearance of metformin is > 400 mL/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. After an oral dose, the elimination half-life is approximately 6.5 hours. In cases of impaired renal function, renal clearance decreases in proportion to creatinine clearance and therefore the elimination half-life increases, leading to increased metformin plasma levels.
Indication
Type 2 diabetes mellitus (insulin-dependent) with ineffective diet therapy and exercise regimen, especially in patients with excess body weight;
- as monotherapy or combination therapy in combination with other oral hypoglycemic agents, or in combination with insulin for the treatment of adults.
- as monotherapy or combination therapy with insulin for the treatment of children aged 10 years and older.
To reduce the complications of diabetes in adult patients with type 2 diabetes mellitus and overweight, as a first-line drug after ineffective diet therapy.
Contraindication
– Hypersensitivity to metformin or any other component of the drug;
– diabetic ketoacidosis, diabetic precoma;
– renal failure or impaired renal function (creatinine clearance < 60 ml/min);
– acute conditions with a risk of developing kidney dysfunction, such as:
dehydration, severe infectious diseases, shock;
– acute and chronic diseases that can lead to the development of hypoxia:
heart or respiratory failure, recent myocardial infarction, shock;
– liver failure, acute alcohol poisoning, alcoholism.
Interaction with other medicinal products and other types of interactions
Combinations that are not recommended for use.
Acute alcohol intoxication is associated with an increased risk of lactic acidosis, especially in cases of fasting or low-calorie diet, as well as in liver failure. Alcohol and alcohol-containing medications should be avoided during treatment with metformin.
Iodinated radiopaque agents may cause lactic acidosis in diabetic patients with functional renal insufficiency. The drug should be discontinued prior to the examination and not resumed earlier than 48 hours after the examination using radiopaque agents and assessment of renal function.
Medicinal products with hyperglycaemic effects (systemic and local glucocorticosteroids, sympathomimetics, chlorpromazine). Blood glucose levels should be monitored regularly, especially at the beginning of treatment. During and after discontinuation of such concomitant therapy, the metformin dose should be adjusted under glycemic control.
Diuretics, especially loop diuretics, may increase the risk of lactic acidosis due to possible decreased renal function.
Application features
Lactic acidosis is a rare but serious metabolic complication that may occur as a result of metformin hydrochloride accumulation. Cases of lactic acidosis have been reported in diabetic patients with severe renal impairment. Risk factors for lactic acidosis include poorly controlled diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, hepatic insufficiency, or any condition associated with hypoxia.
Lactic acidosis may manifest as muscle cramps with abdominal pain and severe asthenia. In the future, acidotic dyspnea, abdominal pain, hypothermia and coma may develop. Diagnostic indicators: laboratory decrease in blood pH, increase in serum lactate concentration above 5 mmol/l, increase in anion gap and lactate/pyruvate ratio. If lactic acidosis is suspected, the drug should be discontinued and the patient should be hospitalized immediately.
Renal insufficiency: Since metformin is excreted by the kidneys, serum creatinine levels should be monitored before and during metformin treatment:
– patients with normal kidney function at least once a year;
– patients with impaired kidney function and elderly patients at least 2-4 times a year.
Caution should be exercised in cases where renal function may be impaired, for example, at the beginning of treatment with antihypertensive agents, diuretics and at the beginning of therapy with non-steroidal anti-inflammatory drugs.
Iodinated radiopaque agents. Intravenous administration of radiopaque agents may cause renal failure, resulting in metformin accumulation and lactic acidosis. Therefore, depending on renal function, metformin should be discontinued 48 hours before or during the examination and not resumed until 48 hours after the examination and assessment of renal function.
Surgery: The drug should be discontinued 48 hours before elective surgery performed under general, spinal, or epidural anesthesia and not resumed until 48 hours after surgery and assessment of renal function.
Children and adolescents. Before starting treatment with metformin, a diagnosis of type 2 diabetes mellitus should be confirmed. Clinical studies have not shown any effect of metformin on height and puberty in children. However, there is no data on the effect of metformin on height and puberty with long-term use, so careful monitoring of these parameters is recommended in children aged 10-12 years who are treated with the drug, especially during puberty.
Other precautions: Patients should follow a diet with a balanced intake of carbohydrates throughout the day. Overweight patients should continue to follow a low-calorie diet. Laboratory values should be monitored regularly.
When metformin is used simultaneously with insulin or other oral hypoglycemic agents (e.g. sulfonylurea derivatives or meglitinides), an increase in the hypoglycemic effect is possible.
Use during pregnancy or breastfeeding
Uncontrolled diabetes during pregnancy (gestational or permanent) increases the risk of congenital anomalies and perinatal mortality. There are limited data from the use of metformin in pregnant women, which do not indicate an increased risk of congenital anomalies. Preclinical studies have not revealed any negative effects on pregnancy, embryonic development, childbirth and postnatal development. In case of planning pregnancy, as well as in case of pregnancy, metformin therapy should be discontinued, a doctor should be informed and insulin therapy should be prescribed to maintain blood glucose levels.
Breastfeeding. Metformin is excreted in breast milk. No adverse effects have been observed in newborns/infants. However, due to insufficient data on the safety of the drug, breastfeeding is not recommended during metformin therapy. A decision on whether to discontinue breastfeeding should be made taking into account the need for the drug for the mother and the potential risk to the child.
Fertility: Metformin had no effect on male or female fertility at doses of 600 mg/kg/day, which is almost 3 times the maximum recommended daily human dose based on body surface area.
Ability to influence reaction speed when driving vehicles or other mechanisms
However, caution should be exercised when metformin is used in combination with other hypoglycemic agents (sulfonylureas, insulin, repaglinide, meglitinides) due to the risk of hypoglycemia.
Method of administration and doses
Monotherapy or combination therapy compatible with other oral hypoglycemic agents.
Adults: The usual starting dose is 500 mg or 850 mg 2-3 times daily with or after meals.
After 10-15 days of treatment, the dose should be adjusted according to the results of serum glucose measurements.
Slowly increasing the dose helps reduce side effects from the digestive tract.
The maximum recommended dose is 3000 mg per day, divided into 3 doses.
In case of switching to metformin treatment, it is necessary to stop taking another antidiabetic agent.
Combination therapy is compatible with insulin.
To achieve better blood glucose control, metformin and insulin can be used as combination therapy. The usual starting dose is 500 mg or 850 mg of metformin 2-3 times daily, while the insulin dose should be adjusted according to serum glucose measurements.
Monotherapy or combination therapy compatible with insulin.
Children. Metformin should be used in children aged 10 years and older. The usual starting dose is 500 mg or 850 mg once daily with or after meals. After 10-15 days of treatment, the dose should be adjusted according to serum glucose measurements.
Slowly increasing the dose helps reduce side effects from the digestive tract.
The maximum recommended dose is 2000 mg per day, divided into 2-3 doses.
Elderly patients may have decreased renal function, therefore the dose of metformin should be selected based on assessment of renal function, which should be performed regularly (see section "Special warnings and precautions for use").
Children. The drug can be used to treat children aged 10 years and older.
Overdose
When using the drug in a dose of 85 g, hypoglycemia was not observed. However, in this case, the development of lactic acidosis was observed. In the event of lactic acidosis, treatment with the drug must be discontinued and the patient urgently hospitalized. The most effective measure for removing lactate and metformin from the body is hemodialysis.
Adverse reactions
Frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000) and isolated cases.
Metabolic: very rarely, lactic acidosis (requires discontinuation of treatment). With prolonged use of the drug, absorption of vitamin B12 may decrease, which is accompanied by a decrease in its level in the blood serum. Observed when prescribing metformin to patients with megaloblastic anemia.
Nervous system: common - taste disturbances.
From the digestive tract: very common - nausea, vomiting, diarrhea, flatulence, lack of appetite, abdominal pain. Most often, these side effects occur at the beginning of treatment and, as a rule, disappear spontaneously. To prevent the occurrence of side effects from the digestive tract, it is recommended to slowly increase the dose and use the drug 2-3 times a day during or after meals.
On the part of the hepatobiliary system: very rarely - liver function tests or hepatitis, which completely disappear after metformin withdrawal.
Skin and subcutaneous tissue disorders: very rarely - skin allergic reactions, including rash, erythema, itching, urticaria.
Expiration date
3 years.
Storage conditions
No special storage conditions are required.
Keep out of reach of children.
Packaging
500 mg tablets: 10 tablets in a blister; 3 (10 × 3) or 12 (10 × 12) blisters in a cardboard box.
850 mg tablets: 10 tablets in a blister; 3 (10 × 3) or 12 (10 × 12) blisters in a cardboard box;
12 tablets in a blister; 10 (12 × 10) blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Lek SA, Poland/Lek SA, Poland.
Location of the manufacturer and its business address
95-010 Strykow, Podlipie Str., 16, Poland/16, Podlipie Str., 95-010 Strykow, Poland (full-cycle production);
ul. Domaniewska, 50 C, Warszawa, 02-672, Poland (packaging, batch production).
