Oral hypoglycemic agents, except insulin. Biguanides. PBX code A10V A02.
diabetes mellitus type 2 (insulin-independent) in adults (especially in patients with excess body weight) with poor diet and exercise, as monotherapy or in combination with other oral hypoglycemic drugs or with insulin.
- hypersensitivity to Metformin or to any other component of the drug;
- diabetic ketoacidosis, diabetic coma;
- renal failure or impaired renal function (creatinine clearance
- acute conditions at risk of developing renal impairment, 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.
Method of application and doses
Monotherapy or combination therapy in combination with other oral hypoglycemic agents.
the Recommended initial dose is 1 tablet a day.
after 10-15 days of treatment the dose should be adjusted according to the results of measurements of glucose level in the blood serum. Slowly increasing the dose helps reduce side-effects from the digestive tract. The maximum recommended dose of 4 tablets per day.
Dose take 1 time per day with meals in the evening, increasing by 500 mg every 10-15 days to 2000 mg. If the required level of glycemia can not be achieved when the blood Glucose XR at a maximum dose of 2000 mg, which takes the patient 1 time a day, the dose can be divided into 2 doses (1 time in the morning and 1 time in the evening, during meals). If the required level of glycemia IS not reached, you can use Glucophage, film-coated tablets, in the maximum recommended dose of 3000 mg per day.
for patients who have already been treated with Metformin, the initial dose of Glucophage XR, prolonged release tablets, should be equivalent to the dose of rapid release tablets.
In the case of the transition to the drug Glucophage XR tablet extended release, 500 mg need to stop taking other antidiabetic drugs.
Combination therapy with insulin.
Metformin and insulin can be used as combination therapy to achieve better control of blood glucose levels. Usually the initial dose of Glucophage HR is 1 tablet per day during meals in the evening, then the dose of insulin should be selected in accordance with the results of measuring blood glucose levels.
elderly patientspossible deterioration of renal function, therefore the dose of Metformin should be selected on the basis of an assessment of renal function, which should be performed regularly (see “application Features“). & nbsp;
Frequent adverse reactions, especially at the beginning of treatment are nausea, vomiting, diarrhea, abdominal pain, lack of appetite. These symptoms usually pass on their own.
Side effects by frequency of occurrence are classified into the following categories:
very often, (>1/10), often (>1/100 and<1/10), infrequently (>1/1000 and<1/100), rare (>1/10000 and<1/1000), very rare , including isolated cases (<1/10000).
Metabolic disorders and abuses by power.
Very rarely, lactic acidosis.
prolonged use of the drug in patients with megaloblastic anemia may reduce the absorption of vitamin b12, which is accompanied by a decrease in its level in serum.
from the nervous system.
often taste disturbance.
from the digestive tract.
very often: nausea, vomiting, diarrhea, abdominal pain, lack of appetite. Most often, these side effects occur at the beginning of treatment and, as a rule, spontaneously disappear. To prevent the occurrence of side effects from the digestive tract, a slow increase in the dose of the drug is recommended.
from the digestive system.
Very rarely: impaired liver function or hepatitis that completely disappears after the elimination of Metformin.
on the part of the skin and subcutaneous tissue.
very rare skin allergic reactions including rash, erythema, itching, urticaria.
when using the drug at a dose of 85 g of hypoglycemia was not observed. However, in this case to observe the development of lactic acidosis. In case of development of lactic acidosis treatment Glucophage XR must be stopped and urgently hospitalize the patient. The most effective measure for removal from the body lactate and Metformin is hemodialysis.
Use in pregnancy and lactation
Uncontrolled diabetes during pregnancy (gestational or permanent) increases the risk of congenital abnormalities and perinatal mortality. There are limited data on the use of Metformin in pregnant women, which do not indicate an increased risk of congenital abnormalities. Preclinical studies did not reveal a negative impact on pregnancy, embryonic development, childbirth and postpartum development. In the case of pregnancy planning, as well as in the case of pregnancy, it is necessary to cancel the therapy with Metformin, inform the doctor and prescribe insulin therapy to maintain blood glucose levels.
Lactation.Metformin is excreted in breast milk. No side effects were observed in newborns/infants. However, since there is insufficient data on the safety of the drug, breastfeeding is not recommended during therapy with Glucophage XR. The decision on the termination lactation should take into account the need of the drug for the mother and the potential risk for the baby.
Fertility. Metformin did not affect the fertility of males and females when used at doses of 600 mg/kg/day, which is almost three times higher than the maximum daily dose, which is recommended for use in humans and is calculated based on the surface area of the body.
the Drug is not for use in children as there is no clinical data for this age group of patients.
lactic acidosisis a rare and severe metabolic complication caused by accumulation of Metformin hydrochloride. Reported cases of lactic acidosis in patients with diabetes mellitus and renal insufficiency. Risk factors for lactic acidosis are: poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol consumption, liver failure or any condition associated with hypoxia.
lactic Acidosis can occur in the form of muscle cramps with abdominal pain and severe asthenia. In the future, it is possible to develop acidous shortness of breath, abdominal pain, hypothermia and coma. Diagnostic indicators laboratory reduction of blood pH, increase of serum lactate concentration above 5 mmol/l, increase of anionic interval and lactate/pyruvate ratio. If you suspect lactic acidosis, you should stop using the drug and immediately hospitalize the patient.
Renal failure. Since Metformin is excreted by the kidneys, before and during the treatment of Glucophage XR, it is necessary to check the level of creatinine in the blood serum:
- patients with normal kidney function at least once a year;
- in patients with impaired renal function and in elderly patients aged at least 2-4 times a year.
caution Should be exercised in cases where kidney function may be impaired, for example at the beginning of treatment with antihypertensive drugs, diuretics and at the beginning of NSAIDs therapy.
Iodinated contrast media. Intravenous application of x-ray contrast agents can cause renal failure as a consequence lead to accumulation of Metformin and development of lactic acidosis. Therefore, depending on kidney function, the use of Metformin should be discontinued 48 hours prior to or during the research and not resume earlier than 48 hours after the study and evaluation of kidney function.
Surgical intervention. It is necessary to stop the use of Glucophage XR 48 hours before the planned surgery, which is carried out under General, spinal or peridural anesthesia and not to resume earlier than 48 hours after the operation and evaluation of kidney function.
Other measures. Patients need to follow a diet, even intake of carbohydrates during the day and monitor laboratory parameters. Overweight patients should continue to follow a low-calorie diet. It is necessary to monitor laboratory parameters of glucose level in the blood.
While the use of ХR Glucophage with insulin or other oral hypoglycemic agents (e.g. sulfonylureas or meglitinides) may increase hypoglycemic action.
it is Possible to have fragments of the shell tablets in the faeces. This is a normal phenomenon and has no clinical significance. & nbsp;
Ability to influence the reaction rate when driving motor transport or operating other mechanisms
Glucophage XR does not affect the rate of reaction when driving or operating machinery because monotherapy with the drug does not cause hypoglycemia.
however, Metformin should be used with caution in combination with other hypoglycemic agents (sulfonylurea derivatives, insulin, Repaglinide) due to the risk of hypoglycemia.
Interaction with other medicinal products and other forms of interaction
Combinations that are not recommended.
Acute alcohol intoxicationis associated with an increased risk of lactic acidosis, especially in cases of starvation or low-calorie diet, as well as liver failure. In the treatment of drug Glucophage XR avoid drinking alcohol and medicines containing alcohol.
Iodinated x-ray contrast agentscan lead to the development of lactic acidosis in patients with diabetes mellitus at the background of functional renal failure. The use of xr Glucophage should be discontinued prior to research and should not be resumed earlier than 48 hours after x-ray examination and evaluation of kidney function.
Combinations that should be used with caution.
Medicines, providing gipoglikemisirutee action (corticosteroids systemic and local action, sympathomimetics, chlorpromazine). It is necessary to constantly monitor blood glucose levels, especially at the beginning of treatment. During and after the termination of such joint therapy, it is necessary to adjust the dose of Glucophage XR under the control of glycemic level.
ACE Inhibitorscan reduce the level of glucose in the blood. If necessary, you should adjust the dosage of the drug during joint therapy.
Diuretics, especially loop diuretics,may increase the risk of lactic acidosis.
Metformin – biguanide with antihyperglycemic effect. Reduces blood plasma as the initial level of glucose and glucose levels after meals. It does not stimulate insulin secretion and does not cause hypoglycemic effect.
Metformin acts in three ways:
- leads to a decrease in glucose production in the liver by inhibiting gluconeogenesis and glycogenolysis;
- improves insulin sensitivity in the muscles by improving the capture and utilization of peripheral glucose
- delays the absorption of glucose in the intestine.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen. Increases transport capacity of all types of membrane glucose transporters (GLUT).
Regardless of its effect on blood glucose levels, Metformin has a positive effect on lipid metabolism: it reduces the content of total cholesterol, low density lipoproteins and triglycerides.
.after taking long-release xr Glucophage tablets, the time to reach the maximum plasma concentration (Tmax) is 7:00 (Tmaxfor fast-release tablets is 2.5 hours).
At the equilibrium state, as the use of tablets with quick release, maximum concentration (max) and area under the curve AUC increase disproportionately ingested dose. AUC after a single oral administration of 2000 mg of Metformin in the form of prolonged release tablets similar to AUC, observed after taking 1000 mg of Metformin in the form of rapid release tablets twice a day.
Fluctuations WITHmaxand AUC in individual subjects in the case of taking Metformin tablets with prolonged release compared to the fluctuations observed in the case of taking Metformin tablets with rapid release.
After taking the tablets with extended release on an empty stomach was observed a decrease in AUC by 30% (Cmaxand Tmaxremained unchanged).
the Absorption of Metformin from prolonged release tablets does not change depending on the composition of the food. There is no cumulation with repeated intake of up to 2000 mg of Metformin in the form of tablets with prolonged release.
Distribution.Linking blood plasma proteins is negligible. Metformin penetrates the red blood cells. The maximum concentration in the blood is lower than the maximum concentration in the blood plasma, and is achieved through the same time. Red blood cells most likely represent a secondary compartment of distribution. The average volume of distribution (Vd) ranges from 63-276 l.
Metabolism.Metformin is excreted unchanged in the urine. Metabolites in humans have not been found.
Output.the Renal clearance of Metformin is>400 ml/min, indicating that Metformin is excreted by glomerular filtration and tubular secretion. After dose, the half-life is about 6.5 hours. Renal clearance decreases in proportion to creatinine clearance and therefore the half-life period increases, which leads to an increase in the level of Metformin in blood plasma.
Basic physical and chemical properties
white or almost white, capsule-shaped biconvex with an engraving of “500” on one side.
Store at a temperature not exceeding 25isC. Keep out of reach of children.
15 tablets in a blister. 2 or 4 blisters in a cardboard box.
According to the recipe.
merc Santa S. A. s … France/Merck Sante sas, France.
2 Rue du Pressoir Saint, 45400 Semois, France/2 rue du Pressoir Vert, 45400 Semoy, France.
GLUCOPHAGE XR 500MG TABLET
Glucophage XR 500mg it is used to lower blood sugar levels. Despite the trade mark of the drug as Glucophage XR, in the international classification it is designated as “Metformin”.
- Treatment of diabetes mellitus.
- Monotherapy in combination with insulin.
How to apply
Glucophage XR 500mg drink one tablet in the evening during dinner. After 10-15 days, it is necessary to check the plasma glucose content. With small changes in glucose is recommended to continue the course of the drug without any changes. In the case of increased blood glucose, it is recommended to increase the sewage dose of the drug to two tablets. The maximum dose is 4 tablets. Before use, it is recommended to consult a specialist.
Each package of the drug contains 30 tablets, that is, it is assumed the minimum passage of the course within fifteen days. If you need to extend the course, you should also contact your doctor for advice.
At the beginning of the course, perhaps the lack of appetite, slight stomach aches and nausea. After a few days of taking the drug symptoms disappear.