Glucofage Long, 750 mg 60 pcs

Oral hypoglycemic drug of biguanide group, which reduces both basal and postprandial blood plasma glucose content. It does not stimulate insulin secretion and therefore does not cause hypoglycemia. Increases the sensitivity of peripheral receptors to insulin and glucose utilization by cells. Reduces glucose production by the liver by inhibiting gluconeogenesis and glycogenolysis. Delays absorption of glucose in the intestine.

Metformin stimulates glycogen synthesis by acting on glycogen synthetase. It increases transport capacity of all types of membrane glucose transporters.

With metformin administration, the patient’s body weight either remains stable or decreases moderately.

Metformin has beneficial effects on lipid metabolism: it reduces total cholesterol, LDL, and triglycerides.

Pharmacokinetics

Intake

After oral administration of the drug in the form of sustained release tablet, metformin absorption is slower compared to the metformin normal-release tablet. Time to reach Cmax of metformin when taking Glucofage® Long tablets is 7 hours. At the same time, Tmax for tablets with normal release is 2.5 h.

In the equilibrium state identical to Css of metformin in the form of tablets with a normal release profile, Cmax and AUC do not increase in proportion to the dose. After a single oral dose of 2000 mg of metformin in the form of sustained release tablets, the AUC is similar to that observed after taking 1000 mg of metformin in the form of normally-released tablets 2 times/day.

The Cmax and AUC fluctuations in individual patients when metformin is taken in the form of sustained release tablets are similar to those observed after taking tablets with normal release profile.

The absorption of metformin from sustained release tablets does not vary with food intake.

Distribution

The binding to plasma proteins is insignificant. Cmax in blood is lower than Cmax in plasma and is reached after approximately the same time. The average Vd ranges from 63-276 L.

There is no cumulation when repeatedly taking up to 2000 mg of metformin in the form of sustained release tablets.

Metabolism

No metabolites have been detected in humans.

The T1/2 after oral administration is about 6.5 h. Metformin is excreted unchanged by the kidneys. Renal clearance of metformin is >400 ml/min, indicating that metformin is excreted by glomerular filtration and tubular secretion.

Pharmacokinetics in special clinical cases

In impaired renal function, metformin clearance decreases in proportion to CK and T1/2 is increased, which may lead to increased metformin plasma concentrations.

Indications

Active ingredient

Composition

Excipients:

sodium carmellose – 37.5 mg,

Hypromellose 2208 – 294.24 mg,

Magnesium stearate – 5.3 mg.

How to take, the dosage

The drug is taken orally once a day, with dinner. Tablets are swallowed whole, without chewing, with plenty of liquid.

The dose of Glucofage® Long should be adjusted individually for each patient on the basis of blood glucose measurements.

Glucofage® Long should be taken daily without interruption. In case of discontinuation of treatment the patient should inform the physician.

If another dose is missed, the next dose should be taken at the usual time. Do not double the dose of the drug Glucofage® Long.

Interaction

On the background of functional renal insufficiency in patients with diabetes mellitus, radiological examination with iodine-containing radiopaque contrast agents may cause the development of lactacidosis. Glucofage® Long should be discontinued 48 h before and not resumed until 48 h after radiologic examination with iodine-containing radiopaque agents provided that renal function has been found normal during the examination.

Unrecommended combinations

Ethanol administration increases the risk of lactacidosis during acute alcohol intoxication, especially in cases of malnutrition, low-calorie diet, and hepatic insufficiency. Medications containing ethanol should not be used during treatment.

Combinations requiring caution

Drugs with indirect hyperglycemic effects (e.g., GCS and tetracosactide for systemic and topical use), beta2-adrenomimetics, danazol, chlorpromazine when taken in high doses (100 mg/day) and diuretics: More frequent monitoring of blood glucose concentrations may be required, especially at the beginning of treatment. If necessary, the dose of the drug Glucofage® Long may be adjusted during treatment and after its discontinuation, based on the level of glycemia.

The simultaneous use of “loop” diuretics may lead to the development of lactacidosis due to possible functional renal failure. Glucofage® Long should not be prescribed if IQ is less than 60 ml/min.

Antihypertensive drugs of ACE inhibitor class may decrease blood glucose concentration. If necessary, the dose of metformin should be adjusted.

The concomitant use of Glucofage® Long 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

Lactacidosis is an extremely rare, but serious (high mortality in the absence of emergency treatment) complication that can occur due to metformin cumulation. Cases of lactacidosis in patients treated with metformin occurred mainly in diabetic patients with severe renal insufficiency.

Other associated risk factors, such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol consumption, liver failure, and any condition associated with severe hypoxia should be considered. This may help reduce the incidence of lactacidosis.

The risk of lactacidosis should be considered if nonspecific signs occur, such as muscle cramps accompanied by dyspepsia, abdominal pain, general weakness, and severe malaise.

Lactacidosis is characterized by acidotic dyspnea, vomiting, abdominal pain, muscle cramps and hypothermia followed by coma. Diagnostic laboratory parameters are decreased blood pH (5 mmol/L, elevated anion gap and lactate/pyruvate ratio. If lactacidosis is suspected, discontinue the drug and immediately consult a physician.

Surgical surgeries

The use of metformin should be discontinued 48 hours before elective surgical procedures and may be continued not earlier than 48 hours after, provided that renal function has been found to be normal during examination.

Renal function

Since metformin is excreted by the kidneys, CK should be determined before starting treatment, and regularly thereafter: at least once a year in patients with normal renal function, and 2-4 times a year in elderly patients, and in patients with CK at the lower end of normal.

Particular caution should be exercised if renal function may be impaired in elderly patients, if hypotensive drugs, diuretics or NSAIDs are used concomitantly.

Other precautions

Patients are advised to continue on a diet with an even carbohydrate intake throughout the day.

Patients who are overweight are recommended to continue on a hypocaloric diet (but at least 1000 kcal/day). Patients should also exercise regularly.

Patients should tell their doctor about any treatments they are taking and any infectious diseases, such as respiratory or urinary tract infections.

Standard laboratory tests should be performed regularly to control diabetes.

Metformin does not cause hypoglycemia during monotherapy, but caution is recommended when it is used in combination with insulin or other oral hypoglycemic agents (e.g., sulfonylurea derivatives or repaglinide). Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, palpitations, visual impairment, or impaired concentration.

The patient should be cautioned that inactive components of the drug Glucofage® Long may be excreted unchanged through the intestine, which does not affect the therapeutic activity of the drug.

Impact on driving and operating machinery

Monotherapy with Glucofage® Long does not cause hypoglycemia, and therefore does not affect the ability to drive and operate machinery.

Patients should be cautioned, however, about the risk of hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylurea derivatives, insulin, repaglinide).

Contraindications

The drug should be used with caution in patients aged over 60 years who have severe physical labor due to increased risk of lactacidosis; and during lactation (breast-feeding).

Side effects

Nervous system disorders: common – taste disorders (metallic taste in the mouth).

Digestive system disorders: very often – nausea, vomiting, diarrhea, abdominal pain, lack of appetite. They occur most frequently during the initial period of treatment and in most cases spontaneously disappear. It is recommended that metformin be taken with meals to prevent the symptoms. Slowly increasing the dose may improve gastrointestinal tolerance.

Hepatobiliary system side effects: very rare – impairment of liver function parameters or hepatitis; after withdrawal of metformin the adverse effects disappear completely.

Skin disorders: very rare – erythema, pruritus, urticaria.

Metabolism: very rare – lactacidosis. With prolonged use of metformin, a decrease in absorption of vitamin B12 is possible. If megaloblastic anemia is detected, the possibility of this etiology should be considered.

If any of the side effects listed in the instructions worsen, or other side effects not listed in the instructions are noted, the patient should inform the physician.

Overdose

Treatment: in case of signs of lactacidosis the drug treatment should be stopped immediately, the patient should be urgently hospitalized and, having determined the lactate concentration, the diagnosis should be clarified. The most effective measure for lactate and metformin elimination from the body is hemodialysis. Symptomatic treatment is also carried out.

Pregnancy use

Limited data suggest that metformin use in pregnant women does not increase the risk of birth defects in children.

If pregnancy is planned, and if pregnancy occurs while using metformin, the drug should be withdrawn and insulin therapy should be prescribed. Blood glucose concentrations should be maintained at levels as close to normal as possible to reduce the risk of fetal malformations.

Metformin is excreted with breast milk. Side effects in infants during breastfeeding against the background of metformin administration have not been observed. However, due to the limited data, it is not recommended to use the drug during breastfeeding. 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.

Preventive use in children

The drug is contraindicated in children and adolescents under 18 years of age due to lack of data on its use.

Similarities