Instructions for use Metamin SR prolonged-release tablets 500 mg blister No. 30
Composition
active ingredient: metformin hydrochloride;
1 tablet contains metformin hydrochloride 500 mg;
excipients: microcrystalline cellulose, ethylcellulose, hypromellose, magnesium stearate, colloidal anhydrous silicon dioxide.
Dosage form
Extended-release tablets.
Main physicochemical properties: white, oval-shaped tablets, smooth on both sides.
Pharmacotherapeutic group
Oral hypoglycemic agents, except insulins. Biguanides. ATX 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:
1) inhibits glucose production in the liver by inhibiting gluconeogenesis and glycogenolysis;
2) improves peripheral glucose uptake and utilization in muscles by increasing insulin sensitivity;
3) slows down the absorption of glucose in the intestines.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthetase.
Increases the transport capacity of all types of membrane glucose transporters (GLUT).
Regardless of its effect on glycemia, metformin has a positive effect on lipid metabolism: it reduces total cholesterol, low-density lipoproteins, and triglycerides.
Pharmacokinetics.
Absorption: After oral administration of the extended-release tablet, the time to maximum concentration (Tmax) is 7 hours, while for the immediate-release tablet, it is 2.5 hours.
At steady state, as with immediate-release tablets, the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) increase disproportionately with the administered oral dose. The AUC after a single oral dose of 2000 mg metformin prolonged-release tablets is similar to the AUC observed after 1000 mg metformin immediate-release tablets twice daily.
Variations in Cmax and AUC in some individuals when taking metformin in the form of prolonged-release tablets compared to those when taking metformin in the form of immediate-release tablets.
Although AUC is reduced by 30% when the prolonged-release tablet is taken on an empty stomach, Cmax and Tmax remain unchanged.
The absorption of metformin from prolonged-release tablets is not affected by food. No accumulation is observed with multiple doses of up to 2000 mg of metformin prolonged-release tablets.
Distribution. Plasma protein binding is negligible. Metformin penetrates into erythrocytes. Peak blood concentrations are lower than peak plasma concentrations and are reached in approximately the same time frame. Erythrocytes are likely to represent a second distribution compartment. 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. This indicates 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 renal impairment, renal clearance decreases in proportion to creatinine clearance, resulting in an increase in the elimination half-life, leading to increased metformin plasma levels.
Indication
Type II diabetes mellitus (non-insulin-dependent) in adults (especially in overweight patients) when diet therapy and exercise are ineffective, as monotherapy or in combination with other oral antidiabetic agents, or in combination with insulin.
Contraindication
– Hypersensitivity to metformin or any other component of the drug;
– diabetic ketoacidosis, diabetic precoma;
– moderate (stage IIIb) and severe renal failure or impaired renal function (creatinine clearance < 45 ml/min or GFR < 45 ml/min/1.73 m2);
– acute conditions that occur with a risk of developing kidney dysfunction, such as: dehydration, severe infectious diseases, shock;
– diseases that can lead to the development of hypoxia (especially acute diseases or exacerbation of a chronic disease): decompensated heart failure, 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.
Iodinated radiocontrast agents: Intravenous administration of iodinated radiocontrast agents may lead to renal failure and, as a result, metformin accumulation and an increased risk of lactic acidosis.
In patients with GFR > 60 ml/min/1.73 m2, metformin should be discontinued prior to or at the time of the test and not resumed until 48 hours after the test, only after re-evaluation of renal function and confirmation of no further deterioration of renal function (see section 4.4).
In patients with moderate renal impairment (GFR 45-60 mL/min/1.73 m2), metformin should be discontinued 48 hours prior to the administration of iodinated radiocontrast agents and not resumed until 48 hours after the examination, only after re-evaluation of renal function and confirmation of no further deterioration of renal function.
Combinations that should be used with caution.
Drugs that have a hyperglycemic effect (glucocorticosteroids of systemic and local action, sympathomimetics, chlorpromazine). It is necessary to monitor the blood glucose level more often, especially at the beginning of treatment. During and after discontinuation of such concomitant therapy, it is necessary to adjust the dose of Metamin®SR under the control of the glycemia level.
ACE inhibitors may lower blood glucose levels. If necessary, the dosage of the drug should be adjusted during concomitant therapy.
Diuretics, especially loop diuretics, may increase the risk of lactic acidosis due to possible decreased renal function.
Application features
Lactic acidosis is a very rare but serious metabolic complication (high mortality rate in the absence of urgent treatment) that may occur as a result of metformin accumulation. Cases of lactic acidosis have been reported in diabetic patients with renal failure or acute deterioration of renal function. Caution should be exercised in cases where renal function may be impaired, for example, in cases of dehydration (severe diarrhea or vomiting), or at the beginning of treatment with antihypertensive agents, diuretics and at the beginning of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). In the event of these exacerbations, metformin should be temporarily discontinued.
Other risk factors for lactic acidosis should be considered: poorly controlled diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, hepatic insufficiency or any condition associated with hypoxia (decompensated heart failure, acute myocardial infarction) (see section "Contraindications").
Lactic acidosis may manifest as muscle cramps, indigestion, abdominal pain and severe asthenia. Patients should immediately inform their doctor about the occurrence of such reactions, especially if they have previously tolerated metformin well. In such cases, metformin should be temporarily discontinued until the situation is clarified. Metformin therapy should be resumed after assessing the benefit/risk ratio in individual cases and assessing renal function.
Diagnostics. Lactic acidosis is characterized by acidotic dyspnea, abdominal pain, and hypothermia, and may progress to coma. Diagnostic indicators: laboratory decrease in blood pH, increase in serum lactate concentration above 5 mmol/L, increase in anion gap, and lactate/pyruvate ratio.
In case of lactic acidosis, the patient should be hospitalized immediately (see section "Overdose"). The physician should warn patients about the risk of developing and the symptoms of lactic acidosis.
Renal failure. Since metformin is excreted by the kidneys, creatinine clearance (can be estimated from plasma creatinine levels using the Cockcroft-Gault formula) or GFR should be checked before starting and regularly during treatment with Metamin®SR:
– patients with normal kidney function at least once a year;
– patients with creatinine clearance at the lower limit of normal and elderly patients at least 2-4 times a year.
In case of creatinine clearance < 45 ml/min (GFR < 45 ml/min/1.73 m2), the use of metformin is contraindicated (see section "Contraindications").
Decreased renal function is common in the elderly and is asymptomatic. Caution should be exercised in situations where renal function may be impaired, such as dehydration or at the beginning of treatment with antihypertensive agents, diuretics and at the beginning of therapy with non-steroidal anti-inflammatory drugs (NSAIDs). In such cases, it is also recommended to check renal function before starting treatment with metformin.
Iodinated radiocontrast agents. Intravenous administration of radiocontrast agents for radiological examinations may cause renal failure, and consequently lead to metformin accumulation and an increased risk of lactic acidosis. In patients with a GFR > 60 ml/min/1.73 m2, metformin should be discontinued prior to or at the time of the examination and not resumed until 48 hours after the examination, only after re-evaluation of renal function and confirmation of the absence of further deterioration of renal function (see section 4.5).
In patients with moderate renal impairment (GFR 45-60 ml/min/1.73 m2), metformin should be discontinued 48 hours before the administration of iodinated radiocontrast agents and not resumed earlier than 48 hours after the examination, only after re-evaluation of renal function and confirmation of the absence of further deterioration of renal function (see section 4.5).
Surgical interventions. Metamin®SR should be discontinued 48 hours before elective surgery performed under general, spinal, or epidural anesthesia and not resumed earlier than 48 hours after surgery or resumption of oral nutrition and only if normal renal function has been established.
Other precautions: Patients should follow a diet, maintain a balanced carbohydrate intake throughout the day, and monitor laboratory parameters. Overweight patients should continue to follow a low-calorie diet. Carbohydrate metabolism should be monitored regularly.
Metformin monotherapy does not cause hypoglycemia, but caution should be exercised when metformin is used concomitantly with insulin or other oral hypoglycemic agents (e.g., sulfonylureas or meglitinides).
The presence of inactive ingredients in the form of a soft mass, which may resemble a tablet, in the feces is possible. This is normal and has no clinical significance.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine, as this medicine contains lactose.
Use during pregnancy or breastfeeding
Pregnancy. 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 adverse effects on pregnancy, embryonal or foetal development, labour and postnatal development. In cases of planning pregnancy, as well as in cases of pregnancy, it is recommended to use insulin, not metformin, to treat diabetes to maintain blood glucose levels as close to normal as possible, in order to reduce the risk of foetal malformations.
Breastfeeding. Metformin is excreted in human milk, but no adverse effects have been observed in breastfed 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 benefit of breastfeeding and the potential risk of adverse effects to the child.
Fertility: Metformin had no effect on the fertility of male and female rats at doses of 600 mg/kg/day, which is almost three times the maximum recommended daily dose for humans based on body surface area.
Ability to influence reaction speed when driving vehicles or other mechanisms
Monotherapy with metformin does not affect the speed of reactions when driving or working with other mechanisms, since the drug does not cause hypoglycemia.
However, caution should be exercised when using metformin in combination with other hypoglycemic agents (sulfonylureas, insulin or meglitidines) due to the risk of hypoglycemia.
Method of administration and doses
Monotherapy or combination therapy in combination with other oral hypoglycemic agents.
The recommended starting dose is 500 mg (1 tablet) per day.
After 10-15 days, the dose should be adjusted according to the results of serum glucose measurements. A slow increase in dose helps to reduce gastrointestinal side effects. The maximum recommended dose is 2000 mg (4 tablets) per day.
For patients already treated with metformin, the initial dose of Metamin® SR, prolonged-release tablets should be equivalent to the daily dose of immediate-release tablets. It is not recommended to switch to Metamin® SR, prolonged-release tablets in patients treated with metformin at a dose of more than 2000 mg.
In case of switching from another antidiabetic agent, this agent should be discontinued and metformin should be prescribed as described above.
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 of Metformin® SR is 500 mg (1 tablet) per day with the evening meal, while the insulin dose should be adjusted according to blood glucose measurements.
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").
Patients with renal impairment. Metformin can be used in patients with moderate renal impairment, stage IIIa (creatinine clearance 45-59 ml/min or GFR 45-59 ml/min/1.73 m2) only in the absence of other conditions that may increase the risk of lactic acidosis, with the following dose adjustment: the initial dose is 500 mg metformin hydrochloride 1 time per day. The maximum dose is 1000 mg per day. Careful monitoring of renal function (every 3-6 months) should be carried out.
If creatinine clearance or GFR decreases to < 45 mL/min or 45 mL/min/1.73 m2, respectively, metformin should be discontinued immediately.
Children
The drug should not be used in children, as there are no clinical data regarding this age group of patients.
Overdose
When using the drug in a dose of 85 g, hypoglycemia was not observed. However, in this case, lactic acidosis developed. In the event of lactic acidosis, treatment with Metamin SR should be discontinued and the patient urgently hospitalized. The most effective measure for removing lactate and metformin from the body is hemodialysis.
Adverse reactions
Metabolic and nutritional disorders: lactic acidosis (see section "Special warnings and precautions for use").
With prolonged use of the drug in patients with megaloblastic anemia, the absorption of vitamin B12 may decrease, which is accompanied by a decrease in its level in the blood serum.
It is recommended to consider this possible cause of B12 hypovitaminosis if the patient has megaloblastic anemia.
From the nervous system: taste disturbance.
Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain, loss of appetite. These side effects most often occur at the beginning of treatment and, as a rule, disappear spontaneously. To prevent the occurrence of side effects from the digestive tract, a slow increase in the dose of the drug is recommended.
On the part of the hepatobiliary system: liver function tests or hepatitis, which completely disappear after metformin withdrawal.
Skin and subcutaneous tissue disorders: allergic skin reactions, including rash, erythema, pruritus, urticaria.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
7 tablets in a blister; 4 blisters in a cardboard box.
15 tablets in a blister, 2 or 6 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
"KUSUM FARM" LLC.
Location of the manufacturer and its business address
40020, Ukraine, Sumy region, Sumy city, Skryabina st., 54.
