Active ingredients: Metformin (metformin hydrochloride)
METFORMIN MYLAN 1000 mg film-coated tablets
Why is Metformin used - Generic Drug? What is it for?
What is Metformin Mylan
Metformin Mylan contains metformin, a medicine used to treat diabetes. It belongs to a group of medicines called biguanides.
Insulin is a hormone produced by the pancreas that allows the body to take glucose (sugar) from the blood. The body uses glucose for energy or stores it for future use.
If you have diabetes, your pancreas does not make enough insulin or your body is unable to use the insulin it produces properly. This causes a high level of glucose in the blood. Metformin Mylan helps to lower blood glucose until it reaches as normal as possible.
If you are an overweight adult, taking Metformin Mylan for an extended period of time also helps reduce the risk of complications associated with diabetes.
Metformin Mylan is associated with stable body weight or modest weight loss.
What Metformin Mylan is used for
Metformin Mylan is used to treat patients with type 2 diabetes (also known as non-insulin-dependent diabetes) when diet and exercise alone are not sufficient for adequate control of blood glucose levels. It is particularly used. in overweight patients.
Adults can take Metformin Mylan alone or in combination with other diabetes medicines (medicines taken by mouth or insulin). Children aged 10 years and over and adolescents can take Metformin Mylan alone or in combination with insulin.
Contraindications When Metformin - Generic Drug should not be used
Do not take Metformin Mylan
- If you are allergic (hypersensitive) to metformin or any of the other ingredients of this medicine (see Section 6, "What Metformin Mylan contains")
- if you have kidney or liver problems
- if you have uncontrolled diabetes, such as severe hyperglycaemia or ketoacidosis. Ketoacidosis is a condition characterized by the "accumulation in the blood of substances called 'ketone bodies'. Symptoms include stomach pains, rapid and deep breathing, sleepiness or an abnormal sweet smell of breath.
- if your body has lost too much water (dehydration), such as if you have severe or prolonged diarrhea, or if you have several consecutive episodes of vomiting. Dehydration can cause kidney problems which can put you at risk for lactic acidosis (see next section "Take special care with Metformin Mylan")
- if you have had a "serious infection, such as" an infection affecting the lung or bronchial system or the kidney. A "serious infection can cause kidney problems that can put you at risk for lactic acidosis (see the next section" Take special care with Metformin Mylan ")
- if you are being treated for heart failure or have recently had a heart attack, have severe circulatory problems or breathing difficulties. This can cause tissue oxygen deficiency which can put you at risk for lactic acidosis (see next section "Take special care with Metformin Mylan")
- if you consume a lot of alcohol
- if you are breast-feeding If any of these apply to you, talk to your doctor before starting to take this medicine.
Precautions for use What you need to know before taking Metformin - Generic Drug
Ask your doctor for advice if
- you must undergo x-ray or scanning tests, which involve the injection of iodine-containing contrast media that enter the bloodstream
- if you are due to undergo major surgery
In this case, you must stop taking Metformin Mylan for a certain period of time before and after the examination or surgery. Your doctor will decide if you need any further treatment. It is important that you follow your doctor's instructions exactly.
Take special care with Metformin Mylan
Metformin Mylan can cause a very rare but serious complication called lactic acidosis, particularly if your kidneys are not working properly. Symptoms of lactic acidosis are vomiting, abdominal pain (abdominal pain) associated with muscle cramps, general feeling of being unwell accompanied by severe tiredness, and difficulty breathing. If you experience these symptoms, you may need immediate treatment. Stop immediately. to take Metformin Mylan and tell your doctor straight away.
Metformin Mylan alone does not cause hypoglycaemia (too low a blood glucose level). However, if you take Metformin Mylan with other medicines used to treat diabetes that can cause hypoglycaemia (such as sulphonylureas, insulin, glinides), there is a risk of hypoglycaemia. If you notice symptoms of low blood sugar such as weakness, dizziness, increased sweating, fast heart rate, visual disturbances or difficulty concentrating, it is generally helpful to have a drink or food containing sugar.
Interactions Which drugs or foods can modify the effect of Metformin - Generic Drug
If you are to be given an "injection of iodine-containing contrast media that enter the bloodstream, for example for x-ray or scanning examinations, you should stop taking Metformin Mylan for a certain period of time before and after the examination (see above 'Ask your doctor for advice if ").
Tell your doctor if you are taking Metformin Mylan and any of the following medicines at the same time. You may need more frequent blood glucose tests or your doctor may adjust your dose of Metformin Mylan:
- angiotensin converting enzyme inhibitors (used to treat many conditions affecting the heart and blood vessels, such as high blood pressure or heart failure)
- diuretics (used to remove water from the body by producing more urine)
- beta-2 agonists, such as salbutamol or terbutaline (used to treat asthma)
- corticosteroids (used to treat many conditions, such as severe inflammation of the skin or in asthma). Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Taking Metformin Mylan with food and drink
Do not drink alcohol while taking this medicine. Alcohol can increase the risk of lactic acidosis, particularly if you have liver problems or are undernourished. This also applies to medicines containing alcohol.
Warnings It is important to know that:
Pregnancy and breastfeeding
During pregnancy she will need insulin to treat her diabetes. Tell your doctor if you are pregnant or think you are pregnant, or if you are considering becoming pregnant, so that they can change your care. Do not take this medicine if you are breastfeeding or if you plan to do so.
Driving and using machines
Metformin Mylan, taken on its own, does not cause hypoglycaemia (low blood glucose). This means that it does not affect your ability to drive or use machines.
However, you will need to be especially careful if you take Metformin Mylan together with other diabetes medicines which can cause hypoglycaemia (such as sulphonylureas, insulin, glinides). Symptoms of hypoglycemia include weakness, dizziness, increased sweating, fast heart rate, visual disturbances or difficulty concentrating. Do not drive or use machines if you experience these symptoms.
Dose, Method and Time of Administration How to use Metformin - Generic Drug: Posology
Always take Metformin Mylan exactly as your doctor has told you. If in doubt, you should consult your doctor or pharmacist.
Metformin Mylan cannot replace the benefits of a healthy lifestyle. Continue to follow all of your doctor's recommendations regarding your diet and exercise regularly.
Usual dose:
Children aged 10 years and over and adolescents usually start with 500 mg or 850 mg of metformin hydrochloride once a day. The maximum daily dose is 2000 mg taken in 2 or 3 divided doses. Treatment of children aged 10 to 12 years is only recommended on specific medical advice, as experience in this age group is limited.
Adult patients usually start with 500 mg or 850 mg of metformin hydrochloride two or three times a day. The maximum daily dose is 3000 mg taken in 3 divided doses.
If you are also taking insulin, your doctor will tell you how to start with Metformin Mylan.
Monitoring
- Your doctor will adjust the dose of Metformin Mylan to your blood glucose levels. Remember to consult with your doctor regularly. This is especially important for children and adolescents or if you are an elderly person.
- Your doctor will also check your kidney function at least once a year. You may need more frequent checks if you are elderly or if your kidneys are not working normally.
How to take Metformin Mylan
Take the tablets with or after a meal. In this way it will avoid unwanted effects on digestion.
You must not crush or chew the tablets. The tablets should be swallowed with a glass of water.
- If you take one dose a day, take it in the morning (with breakfast)
- If you take two divided doses a day, take them in the morning (for breakfast) and in the evening (for dinner)
- If you take three divided doses a day, take them in the morning (for breakfast), at noon (for lunch) and in the evening (for dinner).
If after some time you feel that the effect of Metformin Mylan is too strong or too weak, talk to your doctor or pharmacist.
Overdose What to do if you have taken too much Metformin - Generic Drug
If you take more Metformin Mylan than you should
If you have taken more Metformin Mylan than you should, you may get lactic acidosis. Symptoms of lactic acidosis are vomiting, stomach pain (abdominal pain) associated with muscle cramps, general feeling of being unwell accompanied by severe tiredness and difficulty in breathing. Contact your doctor or pharmacist immediately.
If you forget to take Metformin Mylan
Do not take a double dose to make up for a forgotten dose. Take the next dose as usual.
If you have any further questions on the use of Metformin Mylan, ask your doctor or pharmacist.
Side Effects What are the side effects of Metformin - Generic Drug
Like all medicines, Metformin Mylan can cause side effects, although not everybody gets them.
The following side effects may occur:
Very common side effects (affects more than 1 in 10 patients)
- digestive problems, such as feeling sick (nausea), vomiting, diarrhea, stomach pain (abdominal pain) and loss of appetite. These side effects occur more often at the start of treatment with Metformin Mylan. It may help to divide the doses over the day and take the tablets with or immediately after a meal. If symptoms persist, stop taking Metformin Mylan. and contact your doctor.
Common side effects (in less than 1 in 10 patients)
- changes in taste.
Very rare side effects (in less than 1 out of 10,000 patients)
- Lactic acidosis. This is a very rare but serious complication, particularly if your kidneys are not working properly. If this complication occurs, you may need immediate treatment. Symptoms of lactic acidosis are vomiting, stomach pain (abdominal pain) associated with muscle cramps, general feeling of being unwell accompanied by severe tiredness, and difficulty breathing. experience these symptoms, stop taking Metformin Mylan immediately and tell your doctor straight away.
- Skin reactions such as redness of the skin (erythema), itching or hives.
- Low levels of vitamin B12 in the blood.
The frequency of the following side effects is unknown:
- Abnormal liver function tests or hepatitis (inflammation of the liver; this can cause tiredness, loss of appetite, weight loss, with or without yellowing of the skin or whites of the eyes). If this happens, stop taking this medicine.
Children and adolescents
Limited data in children and adolescents have shown that adverse events are similar in nature and severity to that reported in adults.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep Metformin Mylan out of the reach and sight of children. When treating a child with Metformin Mylan, parents and carers should be advised to read the package leaflet of this medicinal product carefully.
This medicinal product does not require any special storage conditions.
Do not use Metformin Mylan after the expiry date which is stated on the carton or blister after "EXP". The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Metformin Mylan contains
- The active ingredient is metformin hydrochloride. One Metformin Mylan 1000 mg film-coated tablet contains 1000 mg of metformin hydrochloride corresponding to 780 mg of metformin base.
- The other ingredients are povidone K 30, magnesium stearate, hypromellose, macrogol 400 and macrogol 8000.
What Metformin Mylan looks like and contents of the pack
Metformin Mylan 1000 mg film-coated tablets are white, oval and biconvex with a scored line on both sides and with the number "1000" debossed on one side.
The tablet can be divided into equal halves. The tablets are supplied in blisters of: 20, 30, 50, 60, 90, 100, 120, 180, 600 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
METFORMIN MYLAN 1000 MG
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 1000 mg metformin hydrochloride corresponding to 780 mg of metformin base.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
White, oval, biconvex film-coated tablets with a score line on both sides and "1000" engraved on one side. The tablet can be divided into equal halves.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of Type II diabetes mellitus, particularly in overweight patients, when diet and exercise alone are insufficient for adequate glycemic control.
In adults, Metformin Mylan 1000 mg film-coated tablets can be used alone or in combination with other oral antidiabetics or with insulin.
In children over 10 years of age and adolescents, Metformin Mylan 1000 mg film-coated tablets can be used alone or in combination with insulin.
A reduction in diabetes complications has been demonstrated in overweight type 2 diabetic adult patients treated with metformin hydrochloride as first-line therapy after dietary control failure (see section 5.1).
04.2 Posology and method of administration
Adults:
Monotherapy and combination with other oral antidiabetic drugs:
The usual starting dose is 500 mg or 850 mg of metformin hydrochloride 2 or 3 times a day taken with or after meals.
After 10-15 days the dose should be adjusted on the basis of the blood glucose level. A gradual increase in dosage can improve gastrointestinal tolerability.
In patients taking a high dose of metformin hydrochloride (2 to 3 grams per day), two metformin hydrochloride 500 mg film-coated tablets can be replaced with one metformin 1000 mg film-coated tablet.
The maximum recommended dose of metformin hydrochloride is 3 g per day, to be taken in 3 divided doses.
In case of switching from another oral antidiabetic drug: discontinue the previous drug and start with metformin hydrochloride at the dose indicated above.
Combination with insulin:
Metformin hydrochloride and insulin can be used in combination to improve blood glucose control. Metformin hydrochloride is administered at the normal starting dose of 500 mg or 850 mg, 2 or 3 times a day, while the insulin dose is adjusted on the basis of blood glucose.
Senior citizens:
Due to the potential for decreased renal function in elderly subjects, metformin hydrochloride dosage should be adjusted based on renal function. Regular evaluation of renal function is therefore necessary (see section 4.4).
Children and adolescents:
Monotherapy and combination with insulin
Metformin Mylan 1000 mg film-coated tablets can be used in children over 10 years of age and adolescents.
The usual starting dose is 500 mg or 850 mg of metformin hydrochloride once a day, taken with or after a meal.
After 10-15 days the dose should be adjusted on the basis of the blood glucose level. A slow increase in dosage can improve gastrointestinal tolerability. The maximum recommended dosage of metformin hydrochloride is 2 g per day, taken in 2 or 3 divided doses.
04.3 Contraindications
Hypersensitivity to metformin hydrochloride or to any of the excipients.
Diabetic ketoacidosis, diabetic pre-coma.
Renal failure or renal dysfunction (creatinine clearance
Acute conditions with the possibility of impaired renal function such as: dehydration, severe infection, shock, intravascular administration of iodinated contrast agents (see section 4.4).
Acute or chronic diseases that can cause tissue hypoxia such as: heart or respiratory failure, recent myocardial infarction, shock.
Liver failure, acute alcohol intoxication, alcoholism
Feeding time.
04.4 Special warnings and appropriate precautions for use
Lactic acidosis:
Lactic acidosis is a rare but serious (high mortality rate in the absence of rapid treatment) metabolic complication, which may arise following accumulation of metformin hydrochloride. Reported cases of lactic acidosis in patients treated with metformin hydrochloride have occurred particularly in diabetic patients with severe renal insufficiency. The incidence of lactic acidosis can and should be reduced by evaluating other associated risk factors, such as uncontrolled diabetes, ketosis, prolonged fasting, excessive alcohol intake, liver failure and any other conditions associated with hypoxia.
Diagnosis:
The risk of lactic acidosis should be considered if there are nonspecific signs such as muscle cramps combined with digestive system disorders such as abdominal pain and severe asthenia.
Lactic acidosis is characterized by dyspnoea with acidosis, abdominal pain and hypothermia followed by coma. Diagnostic laboratory tests show a decrease in blood pH, plasma lactate levels above 5 mmol / l, and an increase in the anion gap. and lactate / pyruvate ratio If metabolic acidosis is suspected, discontinue metformin hydrochloride and admit the patient immediately (see section 4.9).
Kidney function:
Metformin hydrochloride is excreted by the kidneys, so serum creatinine levels should be determined before starting treatment and regularly thereafter:
at least annually in patients with normal renal function;
at least two to four times a year in patients with serum creatinine levels at the upper limit of normal and in elderly subjects.
Decreased renal function in the elderly is frequent and asymptomatic. Special attention should be paid to situations in which renal function may be compromised, for example when antihypertensive therapy or diuretic therapy is initiated and when therapy with a non-steroidal anti-inflammatory drug is initiated.
Administration of iodinated contrast agents:
Since intravascular administration of iodinated contrast media in radiological studies can lead to renal insufficiency, administration of metformin hydrochloride should be discontinued before or at the time of examination and not resumed until 48 hours after examination, and only after checking whether renal function has returned to normal (see section 4.5).
Surgery:
Administration of metformin hydrochloride should be discontinued 48 hours prior to scheduled surgery under general, spinal or epidural anesthesia. Treatment can be resumed no earlier than 48 hours after surgery or after resuming oral feeding, and only if normal renal function has been ascertained.
Children and adolescents:
The diagnosis of type 2 diabetes mellitus must be confirmed before starting treatment with metformin hydrochloride.
No effects of metformin hydrochloride on growth and puberty have been found in controlled clinical trials lasting one year, but no long-term data are available on these specific points. Therefore, careful follow-up of the effect of metformin hydrochloride on these parameters in children treated with metformin hydrochloride, especially in prepubertia, is recommended.
Children aged 10-12:
Only 15 subjects aged 10 to 12 years were included in the controlled clinical trials conducted in children and adolescents. Although the efficacy and safety of metformin hydrochloride in these children did not differ from those reported for older children and adolescents, special care is recommended when prescribing metformin hydrochloride to children aged 10 to 12 years. .
Other precautions:
Patients should continue their diet by distributing carbohydrates regularly throughout the day. Overweight patients will have to continue the low-calorie diet.
The laboratory tests normally required in cases of diabetes will need to be performed regularly.
Metformin hydrochloride alone does not cause hypoglycaemia, but caution is advised when used in combination with insulin or sulfonylureas.
04.5 Interactions with other medicinal products and other forms of interaction
Combinations not recommended:
Alcohol:
Increased risk of lactic acidosis in acute alcohol poisoning, especially in cases of:
fasting or malnutrition, liver failure.
Avoid consumption of alcohol and alcohol-containing medications.
Iodine contrast agents (see section 4.4):
Intravascular administration of iodinated contrast agents may cause renal failure, resulting in the accumulation of metformin hydrochloride and an increased risk of lactic acidosis.
Administration of metformin hydrochloride should be discontinued before or at the time of the examination and should not be resumed earlier than 48 hours after the examination, and only after checking whether renal function has returned to normal.
Associations requiring precaution:
Glucocorticoids (systemically and locally), beta-2-agonists, and diuretics have intrinsic hyperglycemic activity. Inform the patient and carry out more frequent blood glucose checks, especially at the start of treatment. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and when it is stopped.
ACE inhibitors can reduce blood sugar. Therefore, a dose adjustment of metformin hydrochloride is required during and after the addition or discontinuation of these medicinal products.
04.6 Pregnancy and lactation
No relevant epidemiological data are available so far. Animal studies do not indicate harmful effects on pregnancy, embryonic or fetal development, parturition or postnatal development (see section 5.3).
When the patient plans to become pregnant and during pregnancy itself, diabetes should not be treated with metformin hydrochloride but insulin should be used to keep blood sugar as close to normal as possible, in order to reduce the risk of fetal malformation associated with abnormal blood sugar levels.
In lactating mice, metformin hydrochloride is excreted in milk. For humans, similar data are not available and a decision must therefore be made whether to discontinue breastfeeding or to discontinue metformin hydrochloride, considering the importance that the compound has for the mother.
04.7 Effects on ability to drive and use machines
Metformin hydrochloride alone does not cause hypoglycaemia, therefore it has no effect on the ability to drive or use machines.
However, patients should be advised of the risk of hypoglycaemia when metformin hydrochloride is used in combination with other antidiabetic drugs (sulfonylureas, insulin, repaglinide).
04.8 Undesirable effects
The following side effects may occur during treatment with metformin hydrochloride. Their frequency is defined as follows: very common: ≥ 1/10; common ≥1 / 100,
Within each frequency class, undesirable effects are reported in descending order of severity.
Nervous system disorders:
Common: changes in taste
Gastrointestinal disorders:
Very common: changes in the gastrointestinal tract such as nausea, vomiting, diarrhea, abdominal pain and loss of appetite. These side effects occur more frequently during the initiation of therapy and resolve spontaneously in most cases. To prevent them, it is recommended that metformin hydrochloride be taken in 2 or 3 daily doses during or after meals. A slow increase in dosage is also recommended. can improve gastrointestinal tolerability.
Skin and subcutaneous tissue disorders:
Very rare: skin reactions such as erythema, itching, hives
Metabolism and nutrition disorders:
Very rare:
lactic acidosis (see section 4.4).
Decreased absorption of vitamin B12 with decreased serum levels during long-term use of metformin hydrochloride. It is recommended that this etiology be considered in patients with megaloblastic anemia.
Hepatobiliary disorders:
Not known: changes in liver function tests or hepatitis which resolved following discontinuation of metformin hydrochloride.
In published and post-marketing data, and in controlled clinical trials in a limited pediatric population aged 10 to 16 years treated for one year, adverse event reports were similar in severity and nature to those reported for adults.
04.9 Overdose
No forms of hypoglycaemia have been observed with metformin hydrochloride dosages up to 85 g, although lactic acidosis has developed under such circumstances. Heavy metformin hydrochloride overdoses or concomitant risks may lead to lactic acidosis. Lactic acidosis is an emergency medical case and should be treated in a hospital. The most effective method of eliminating lactate and metformin hydrochloride is hemodialysis.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: drugs that lower blood glucose. Biguanide; ATC code: A10BA02
Metformin hydrochloride is a biguanide with antiperglycemic effects, which reduces basal and postprandial blood glucose. It does not stimulate insulin secretion and therefore does not cause hypoglycemia.
Metformin hydrochloride can act through 3 mechanisms:
reduction of hepatic glucose production through inhibition of gluconeogenesis and glycogenolysis;
in the muscles, increasing insulin sensitivity, improving the absorption and use of peripheral glucose;
delaying intestinal absorption of glucose.
Metformin hydrochloride stimulates intracellular glycogenosynthesis by acting on glycogen synthetase.
Metformin hydrochloride increases the transport capacity of all types of glucose membrane transporters (GLUTs) known to date.
In humans, regardless of its action on glycaemia, metformin hydrochloride has favorable effects on lipid metabolism. This phenomenon has been demonstrated in controlled medium- and long-term clinical studies at therapeutic doses: metformin hydrochloride reduces the levels of total cholesterol, LDL cholesterol and triglycerides.
Clinical efficacy:
The prospective randomized study (UKPDS) demonstrated the long-term benefit of intensive blood glucose control in adult patients with type 2 diabetes.
Analyzes of outcomes on overweight patients treated with metformin hydrochloride after dietary failure alone demonstrated the following.
A significant reduction in the absolute risk of diabetes-related complications in the metformin hydrochloride group (29.8 events per 1000 patients per year) compared to the diet alone (43.3 events per 1000 patients per year), p = 0.0023 , and compared to the insulin and sulfonylurea monotherapy groups (40.1 events per 1000 patients per year), p = 0.0034.
A significant reduction in diabetes-related mortality: metformin hydrochloride 7.5 events per 1000 patients per year, diet alone 12.7 events per 1000 patients per year, p = 0.017;
A significant reduction in the absolute risk of overall mortality: metformin hydrochloride 13.5 events per 1000 patient per year versus diet alone 20.6 events per 1000 patient per year (p = 0.011), and versus insulin monotherapy groups and sulfonylureas 18.9 events per 1000 patients per year (p = 0.021);
A significant reduction in the absolute risk of myocardial infarction: metformin hydrochloride 11 events per 1000 patients per year, diet alone 18 events per 1000 patients per year (p = 0.01).
There was no clinical benefit found for metformin hydrochloride used as second-line therapy in combination with a sulfonylurea.
In cases of type 1 diabetes, the combination of metformin hydrochloride and insulin has been used on selected patients but the clinical benefit of this combination has not been formally determined.
Controlled clinical trials in a limited pediatric population between 10 and 16 years treated for one year have shown a response in terms of glycemic control similar to that of adults.
05.2 "Pharmacokinetic properties
Absorption:
After an oral dose of metformin hydrochloride, T is reached in 2.5 hours. The absolute bioavailability of a 500 mg or 850 mg metformin hydrochloride tablet is approximately 50-60% in healthy subjects. After an oral dose the unabsorbed fraction found in faeces was 20-30%.
After oral administration, the absorption of metformin hydrochloride is saturable and incomplete. The absorption pharmacokinetics of metformin hydrochloride are assumed to be non-linear.
At metformin hydrochloride dosages and recommended dosing schedules, equilibrium plasma concentrations are achieved within 24 to 48 hours and are generally less than 1 mcg / mL. In controlled clinical trials, maximum plasma metformin hydrochloride levels (Cmax) did not exceed 4 mcg / mL, even at maximum doses.
Feeding reduces and slightly delays the absorption of metformin hydrochloride. Following administration of a dose of 850 mg, a 40% lower peak plasma concentration, a 25% decrease in AUC (area under the curve) and a 35 minute prolongation of the time to arrive were observed. at peak plasma concentration The clinical relevance of these findings is unknown.
Distribution:
Plasma protein binding is negligible. Metformin hydrochloride distributes into erythrocytes. The peak in blood is less than the peak in plasma and appears around the same time. The erythrocytes most likely represent a secondary compartment of distribution. The mean value of Volume of distribution (Vd) is between 63 and 276 l.
Metabolism:
Metformin hydrochloride is secreted unchanged in the urine. No metabolites have been identified in humans.
Elimination:
The renal clearance index of metformin hydrochloride is> 400 ml / min: this indicates that metformin hydrochloride is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6, 5 hours.
When renal function is impaired, renal clearance decreases in proportion to that of creatinine, resulting in prolonged elimination half-life and increased plasma metformin hydrochloride levels.
Children and adolescents:
Single dose study: After single doses of 500 mg metformin hydrochloride, pediatric patients demonstrated a similar pharmacokinetic profile to that seen in healthy adults.
Repeated dose studies: Data are limited to one study. After repeated doses of 500 mg twice daily for 7 days in pediatric patients, peak plasma concentration (Cmax) and systemic exposure (AUC0-t) were reduced by approximately 33% and 40%, respectively, in comparison. to diabetic adults treated with repeated doses of 500 mg twice daily for 14 days Since the dose is individually titrated based on glycemic control, this fact is of limited clinical relevance.
05.3 Preclinical safety data
Pre-clinical data reveal no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet:
povidone 30 K, magnesium stearate.
Coating:
hypromellose, macrogol 400, macrogol 8000.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
20, 30, 50, 60, 90, 100, 120, 180, 600 tablets in blisters (PVC-aluminum).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
MYLAN S.p.A.
Via Vittor Pisani 24
20124- Milan
08.0 MARKETING AUTHORIZATION NUMBER
20 film-coated tablets AIC n 035408018 / M
30 film-coated tablets AIC n 035408020 / M
50 film-coated tablets AIC n 035408032 / M
60 film-coated tablets AIC n 035408044 / M
90 film-coated tablets AIC n 035408057 / M
100 film-coated tablets AIC n 035408069 / M
120 film-coated tablets AIC n 035408071 / M
180 film-coated tablets AIC n 035408083 / M
600 film-coated tablets AIC n 035408095 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
January 15, 2002 / February 2006
10.0 DATE OF REVISION OF THE TEXT
October 2010
