Metformin, 850 mg 60 pcs

Pharmacotherapeutic group: Hypoglycemic drug of oral biguanide group.

ATX code: A10BA02

Pharmacological properties

.Pharmacodynamics

Metformin reduces hyperglycemia without leading to hypoglycemia. Unlike sulfonylurea derivatives, it does not stimulate insulin secretion and has no hypoglycemic effect in healthy individuals. Increases the sensitivity of peripheral receptors to insulin and glucose utilization by cells. Inhibits gluconeogenesis in the liver, delays carbohydrate absorption in the intestine. Stimulates glycogen synthesis by activating glycogen synthase. Increases the transport capacity of all types of membrane glucose transporters.

In addition, it has favorable effects on lipid metabolism: it reduces the levels of total cholesterol, low-density lipoproteins and triglycerides.

By taking metformin, a patient’s body weight either remains stable or decreases moderately.

Pharmacokinetics

Absorption<

Metformin is rapidly absorbed in the gastrointestinal tract (GIT). Absolute bioavailability is 50-60%. Maximum concentration (C_max) in blood plasma is approximately 2 µg/ml. Time to reach C_max is 2.5 h. Absorption of metformin is decreased and delayed with concomitant food intake.

Distribution

Metformin is rapidly distributed in tissues, almost does not bind to plasma proteins.

Metabolism and excretion

It is metabolized to a very low degree and excreted by the kidneys. Metformin clearance in healthy subjects is 400 ml/min (4 times greater than creatinine clearance), indicating the presence of active tubular secretion. The elimination half-life (T_1/2) is about 6.5 h.

Pharmacokinetics in special groups of patients

In patients with renal impairment the T_1/2 increases, there is a risk of metformin cumulation in the body.

Indications

Type 2 diabetes mellitus, especially in obese patients, when diet therapy and physical activity are ineffective:

Active ingredient

Composition

How to take, the dosage

The drug Metformin is taken orally, during or immediately after a meal, without chewing, with plenty of water.

Adults

Monotherapy and combination therapy in combination with other oral hypoglycemic agents

Interaction

Contraindicated combinations

Iodine-containing radiopaque agents:In a background of functional renal insufficiency in patients with diabetes mellitus, radiological examination with iodine-containing radiopaque contrast agents may cause the development of lactoacidosis. Metformin treatment should be discontinued depending on renal function 48 hours before or at the time of radiological study with iodine-containing radiopaque agents and not resumed until 48 hours after, provided that renal function has been found normal during the examination.

Unrecommended combinations

Alcohol:In acute alcohol intoxication, there is an increased risk of lactoacidosis, especially in cases of malnutrition; compliance with a low-calorie diet; in cases of hepatic insufficiency. Alcohol and medicinal products containing ethanol should be avoided while taking the drug.

Combinations requiring use with caution

Danazole: concomitant administration of danazol is not recommended to avoid the hyperglycemic effects of the latter; if treatment with danazol is necessary and after discontinuation of the latter, correction of the metformin dose under control of blood glucose concentrations is required.

Chlorpromazine when taken in high doses (100 mg/day) increases blood glucose concentration, reducing insulin release. During treatment with neuroleptics and after discontinuation of their use metformin dose adjustment is required with monitoring of blood glucose concentrations.

Glucocorticosteroids (GCS) of systemic and local action decrease glucose tolerance and increase blood glucose concentration, sometimes causing ketosis. During treatment with GCS and after discontinuation of GCS, metformin dose adjustment is required under control of blood glucose concentration.

Diuretics:Concomitant use of “loop” diuretics may lead to lactoacidosis due to possible functional renal failure. Metformin should not be taken if the CK is below 60 mL/min.

Beta2-adrenomimetics administered parenterally increase blood glucose concentration due to beta-adrenoreceptor stimulation. In this case it is necessary to control blood glucose concentration. If necessary insulin administration is recommended.

When concomitant use of the above drugs may require more frequent monitoring of blood glucose, especially at the beginning of treatment. If necessary, the dose of metformin may be adjusted during treatment and after discontinuation.

Angiotensin-converting enzyme (ACE) inhibitors and other hypotensive drugs may decrease blood glucose concentrations. The dose of metformin should be adjusted if necessary.

Concomitant use of metformin with sulfonylurea derivatives, insulin, acarbose, salicylates may cause hypoglycemia.

Nifedipine increases absorption and Cmax of metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) that are secreted in the renal tubules compete with metformin for tubular transport systems and may increase its Cmax.

Special Instructions

Lactoacidosis

Lactoacidosis is a rare but serious (high mortality if not treated urgently) complication that can occur due to metformin cumulation. Cases of lactoacidosis when taking metformin have occurred mainly in patients with diabetes mellitus with severe renal insufficiency.

Synopsis

Contraindications

Side effects

Frequency of side effects is estimated as follows:
very often: > 1/10; often: 1/10 – 1/100; infrequent: 1/100 – 1/1000; rare: 1/1000 – 1/10000; very rare: < 1/10000.
Metabolic and nutritional disorders: very rare – lactoacidosis (see “Special Precautions”).
With long-term use of metformin there may be a decrease in absorption of vitamin B12. If interoblastic anemia is detected, the possibility of this etiology should be considered.
Nervous system disorders: often – taste disorder.
Gastrointestinal disorders: very often – nausea, vomiting, diarrhea, lack of appetite, abdominal pain.
These side effects are most likely in the initial period of metformin administration and in most cases, when continued use, they spontaneously go away. To reduce side effects, it is recommended that the drug be taken with or after meals. Slowly increasing the dose may improve gastrointestinal tolerance.
Disorders of the liver and biliary tract: very rare – liver dysfunction, hepatitis.
After withdrawal of metformin, these adverse events disappear completely.
Disorders of the skin and subcutaneous tissues: very rare – skin reactions such as erythema, itching, rash.
Published post-marketing data and data from controlled clinical trials in a limited pediatric population in the age group of 10-16 years show that side effects in children are similar in nature and severity to those in adult patients.

Overdose

Pregnancy use

Decompensated diabetes mellitus during pregnancy is associated with an increased risk of birth defects and perinatal mortality.
Limited data suggest that metformin use in pregnant women does not increase the risk of birth defects in children. If pregnancy is planned, or if pregnancy occurs while taking metformin, the drug should be withdrawn and insulin therapy should be prescribed. It is necessary to maintain plasma glucose levels as close to normal as possible to reduce the risk of fetal malformations.
Metformin penetrates into breast milk. Side effects in newborns during breastfeeding have not been observed with metformin. However, due to limited data, the use of metformin during breastfeeding is not recommended. The decision to discontinue breastfeeding should be made taking into account the benefits of breastfeeding and the potential risk of side effects in the baby.

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