Metformin Canon, 1000 mg 30 pcs

Pharmgroup:

Hypoglycemic drug of the group of biguanides for oral use.

Pharmic action:

Metformin is an oral hypoglycemic agent of the biguanide group. In patients with diabetes, it decreases the blood glucose concentration by inhibiting gluconeogenesis in the liver, reducing the absorption of glucose from the gastrointestinal tract (GIT) and increasing its utilization in tissues by increasing their sensitivity to insulin (mainly in striated muscles and to a lesser extent in adipose tissue). It stimulates intracellular glycogenesis by activating glycogen synthase.

In contrast to sulfonylurea derivatives it does not stimulate insulin secretion and has no hypoglycemic effect in healthy individuals. It has an effect on lipid metabolism – reduces the concentration of triglycerides, cholesterol and low-density lipoproteins in the blood serum. Stabilizes or reduces body weight. It has a fibrinolytic effect due to inhibition of tissue-type plasminogen activator inhibitor.

Pharmacokinetics:

After oral administration, absorption of metformin from the gastrointestinal tract is 48-52%. Absorption of metformin is decreased and delayed with concomitant food intake. Absolute bioavailability is 50-60 %. Maximal concentration in blood (Cmax) is 2 µg/ml, time to reach maximal concentration (TCmax) is 1.81-2.69 h.

Metformin is rapidly distributed in tissues. It penetrates into erythrocytes. It accumulates in the salivary glands, liver and kidneys. The volume of distribution (for a dose of 850 mg) is 296-1012 l. Binding to plasma proteins is insignificant. It is metabolized to a very small extent.

Extracted by the kidneys, mainly unchanged. Clearance of metformin in healthy persons is 400 ml/min. Half-life (T1/2) is 6.2 h (initial T1/2 – 1.7 to 3 h, terminal – 9 to 17 h). In renal insufficiency it increases, there is a risk of cumulation of the drug.

Indications

– Type 2 diabetes mellitus in adults (especially in patients with obesity) when diet therapy and physical activity are ineffective, as monotherapy or in combination with other oral hypoglycemic agents or insulin.

– Type 2 diabetes mellitus in children from the age of 10 years – both as monotherapy and in combination with insulin.

Active ingredient

Composition

1 tablet:

– metformin hydrochloride 1000 mg;

supplements:

Pregelatinized starch 78 mg,

sodium carboxymethyl starch (primogel) 16 mg,
.

sodium stearyl fumarate 6 mg,

povidone 94 mg, talc 6 mg;

composition of the film coating:

Opadray II white 36 mg, including: polyvinyl alcohol 16.884 mg, macrogol (polyethylene glycol) 8.496 mg, titanium dioxide 4.356 mg, talc 6.264 mg.

How to take, the dosage

The tablets should be taken orally, swallowed whole, without chewing, during or immediately after a meal, with plenty of water.

Adults:

Monotherapy and combination therapy with other oral hypoglycemic agents
The recommended starting dose is 1000-1500 mg/day. The dose should be divided into 2-3 doses in order to decrease gastrointestinal side effects. In 10-15 days in absence of adverse effects of gastrointestinal tract further gradual dose increase depending on blood glucose concentration is possible. Slow increase in dose may improve gastrointestinal tolerance of the drug.

The maintenance daily dose is 1500-2000 mg. The maximum daily dose is 3000 mg divided into 3 doses.

If planning to switch from another oral hypoglycemic drug to Metformin Canon, discontinue the other hypoglycemic drug and start Metformin Canon in the above doses.

Combination therapy with insulin

The recommended starting dose of Metformin Canon 500 mg and 850 mg is 1 tablet 2-3 times daily, Metformin Canon 1000 mg is 1 tablet once daily, the dose of insulin is adjusted on the basis of blood glucose values.

Children over 10 years of age:

Metformin Canon is used in monotherapy and in combination therapy with insulin.

The recommended starting dose of Metformin Canon is 500 mg once daily in the evening with a meal. In 10-15 days the dose of the drug should be adjusted on the basis of blood glucose concentration. The maintenance dose is 1000-1500 mg/day in 2-3 doses. The maximum daily dose is 2000 mg in 3 doses.

Patients of Elderly People

Because of possible decrease of renal function the dose of drug Metformin Canon should be adjusted with regular control of renal function parameters (serum creatinine concentration control at least 2-4 times per year).
Duration of therapy is determined by the physician. It is not recommended to interrupt the drug without a physician’s indication.

Interaction

Contraindicated combinations:

Radiological studies with iodine-containing radiopaque contrast agents may cause development of lactoacidosis in diabetic patients with functional renal insufficiency. Metformin administration should be discontinued 48 hours before and not resumed until 48 hours after radiological examination with contrast agents.

Unrecommended combinations:

The simultaneous use of metformin with alcohol and ethanol-containing drugs, during acute alcohol intoxication, fasting or following a low-fat diet, and hepatic impairment increases the risk of lactoacidosis.

Combinations requiring special caution:

Concomitant use of metformin with danazol may result in hyperglycemic effects. If treatment with danazolol is necessary and after discontinuation of danazolol, metformin dose adjustment is required under control of blood glucose concentrations.

Chlorpromazine at high doses (100 mg/day) decreases insulin release and increases blood glucose concentrations. When concomitant use with neuroleptics and after discontinuation of their use, correction of metformin dose is required under control of blood glucose concentration.

Glucocorticosteroids (GCS) when used parenterally and topically decrease glucose tolerance and increase blood glucose concentration, in some cases causing ketosis. If it is necessary to use such a combination and after discontinuation of GCS, metformin dose should be adjusted under control of blood glucose concentration.
With the simultaneous use of loop diuretics and metformin there is a risk of lactoacidosis due to the possible appearance of functional renal failure.

The use of beta2-adrenomimetics in the form of injections reduces the hypoglycemic effect of metformin due to stimulation of beta2-adrenoreceptors. In this case, blood glucose concentration should be monitored and insulin should be used if necessary.

Angiotensin-converting enzyme inhibitors and other antihypertensive drugs may decrease blood glucose concentration. If necessary, the dose of metformin should be adjusted.

Concomitant use of metformin with sulfonylurea derivatives, insulin, acarbose and salicylates may increase the hypoglycemic effect.

Nifedipine increases absorption and Cmax of metformin, which should be considered when using them concomitantly.
“Loop” diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of reduced renal function. In this case, caution should be exercised when using metformin.

Special Instructions

During treatment with metformin, blood glucose concentrations should be monitored regularly on an empty stomach and after meals.
The patient should be warned to stop taking the drug and seek medical attention if vomiting, abdominal pain, muscle aches, general weakness, and severe malaise occur. These symptoms may be a sign of early lactoacidosis.

Metformin should be discontinued 48 hours before and 48 hours after radiologic investigation (including urography, intravenous angiography) using radiographic contrast agents.

Because metformin is excreted by the kidneys, creatinine concentrations should be determined before initiating treatment and regularly thereafter: once per year in patients with preserved renal function; 2-4 times per year in patients with decreased CK and in elderly patients.

Particular caution should be exercised if renal function is impaired, e.g., during initial therapy with antihypertensive agents, diuretics, NSAIDs.

Patients should be advised to seek medical attention if they have symptoms of bronchopulmonary infection or urinary tract infections.

Alcohol should be withheld while using metformin due to the increased risk of hypoglycemia and disulfiram-like effects.

Hypovitaminosis B12 when taking metformin is due to impaired absorption and is reversible. Signs of hypovitaminosis of B12 quickly disappear when the drug is discontinued.

Impact on ability to drive and operate vehicles:

Metformin monotherapy does not cause hypoglycemia and therefore does not affect the ability to drive or operate machinery.

When using metformin with other hypoglycemic agents (sulfonylurea derivatives, insulin, etc.) hypoglycemic states may develop, in which the ability to drive vehicles and engage in other potentially dangerous activities requiring increased attention and quick psychomotor reactions is impaired.

Contraindications

– Diabetic ketoacidosis, diabetic precoma, coma.
– Renal insufficiency or renal impairment (creatinine clearance (CK) less than 60 ml/min).
– Acute conditions with the risk of renal dysfunction:
– Dehydration (with diarrhea, vomiting), fever, severe infectious diseases,
– Hypoxic conditions (shock, sepsis, kidney infections, bronchopulmonary diseases).
– Clinical manifestations of acute and chronic diseases that may lead to the development of tissue hypoxia (including cardiac or respiratory failure, acute myocardial infarction).
– Extensive surgical operations and injuries when insulin therapy is indicated (see section “Indications”).
– Liver failure, liver dysfunction.
– Chronic alcoholism, acute alcohol poisoning.
– Lactoacidosis, including in anamnesis.
– Administration for at least 48 hours before and 48 hours after radioisotopic and X-ray examinations with iodine contrast agent (see section “Interaction with other medicinal products”).
– The period of at least 48 hours before and 48 hours after surgical interventions under general anesthesia, spinal or peridural anesthesia.
– Hypo-caloric diet (less than 1000 kcal/day).
– Children under 10 years of age.

With caution: In patients over 60 years of age who perform heavy physical work (increased risk of lactoacidosis).

Side effects

Central nervous system: taste disorder (“metallic” taste in the mouth).

Gastrointestinal disorders: nausea, vomiting, diarrhea, abdominal pain and lack of appetite.

The occurrence of these side effects is most likely during the initial period of treatment and in most cases they go away spontaneously. To prevent symptoms, it is recommended that metformin be taken with or after meals. Slowly increasing the dose may improve gastrointestinal tolerance.

Hepatobiliary system side: impaired liver function parameters, hepatitis. After withdrawal of metformin, adverse events usually disappear completely.

Allergic reactions: very rare – erythema, skin itching, rash, urticaria.

Metabolic disorders: very rare – lactoacidosis (requires cancellation of the drug).

Others: very rare – with long-term use hypovitaminosis of B12 (including megaloblastic anemia) and folic acid (malabsorption) develops.

Published data show that in a limited pediatric population aged 10 to 16 years, side effects are similar in nature and severity to those in adult patients.

Overdose

Symptoms: when using metformin at a dose of 85 g, no hypoglycemia was observed, but the development of lactoacidosis was noted. Early symptoms of lactocidosis are nausea, vomiting, diarrhea, decreased body temperature, abdominal pain, muscle pain; further on, rapid breathing, dizziness, impaired consciousness and development of coma may be noted.

Treatment: In case of signs of lactocidosis the drug treatment shall be stopped immediately, the patient shall be urgently hospitalized and after determining the lactate concentration the diagnosis shall be determined. The most effective measure for lactate and metformin elimination from the body is hemodialysis. Symptomatic treatment is also carried out.

Similarities