Active ingredients: Metformin
SLOWMET 500 mg, 750 mg and 1000 mg prolonged-release tablets
Indications Why is Slowmet used? What is it for?
Metformin belongs to a group of active substances called biguanides which are used to treat diabetes by regulating blood sugar levels. SLOWMET is used for patients with Type 2 diabetes who are intolerant to effective doses of immediate-release metformin due to the onset of severe gastrointestinal side effects and in patients in whom the onset of these effects prevents the achievement of the optimal dose of metformin SLOWMET can be used alone or in combination with other oral antidiabetics or with insulin.
If you need more information, ask your doctor or pharmacist.
Contraindications When Slowmet should not be used
Do not use SLOWMET
- If you are allergic (hypersensitive) to metformin or any of the other ingredients of SLOWMET listed below in section 6.
- If you have diabetic ketoacidosis (a complication of diabetes which may be associated with frequent urination, nausea and vomiting, abdominal (stomach) pain, lethargy and sleepiness) or diabetic precoma (altered mental status due to an imbalance in blood sugar).
- If you have kidney or liver problems.
- If you are dehydrated.
- If you have a severe infection.
- If you are about to receive certain types of injectable marker x-rays (see section "Taking SLOWMET with other medicines").
- If you have recently experienced heart failure.
- If you have recently had a heart attack or have circulatory problems or breathing difficulties. If you are a heavy drinker (whether you drink occasionally or every day).
- If you are breastfeeding.
Precautions for use What you need to know before taking Slowmet
Take special care with SLOWMET
- Metformin treatment can rarely cause a serious condition called lactic acidosis that requires immediate hospitalization to prevent coma. Other illnesses, prolonged fasting or poor blood sugar control, or alcohol intake can all increase. the risk of developing lactic acidosis. You should be aware of the warning symptoms which include muscle cramps, abdominal pain, breathlessness and a feeling of extreme weakness and malaise. If you develop such symptoms, you should notify your doctor immediately.
- Your doctor will check your kidney function at least once a year or more often if necessary.
- If you are about to have anesthesia, x-rays or scans, please tell your doctor that you are taking metformin. It is recommended to stop taking SLOWMET 48 hours before and after the procedure.
- Continue to follow your doctor's directions for your diet and exercise regularly while taking this drug.
- Take care if you are taking SLOWMET with insulin or other antidiabetic medicines as the combination may increase the risk of hypoglycaemia ("hypo" means excessively low blood sugar levels).
Interactions Which drugs or foods can modify the effect of Slowmet
- SLOWMET should not be used concomitantly with injectable contrast media used for certain radiographic or tomographic techniques, as there is a risk of renal failure. If you need to undergo such procedures, you should tell your doctor that you are taking metformin. It is recommended to stop taking SLOWMET 48 hours before and after the procedure.
- Glucocorticoids (eg budesonide, beclomethasone or hydrocortisone, which are sometimes used to suppress inflammation caused by allergic reactions and asthma), beta-2-agonists (eg salbutamol generally used in the treatment of asthma) and diuretics (tablets that increase production urine and can be used to treat hypertension) can all raise blood sugar levels. If you are taking SLOWMET with any of these medicines you should check your blood sugar levels more frequently.
- ACE (Angiotensin Converting Enzyme) inhibitors (eg quinapril, captopril which are used to treat heart problems) can reduce blood sugar levels. Tell your doctor if you start treatment with an ACE inhibitor.
- Use particular caution and tell your doctor if you start treatment for hypertension or treatment with a diuretic (tablets that increase urine production) or NSAIDs (non-steroidal anti-inflammatory drugs, eg ibuprofen). As you may be more prone to risk of kidney disorders.
- Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Taking SLOWMET with food and drink
- SLOWMET should be taken with the evening meal. Taking the tablets with food can reduce unwanted side effects.
- Alcohol consumption or alcohol-containing medications should be avoided during treatment with metformin, as there may be a higher risk of developing lactic acidosis, a serious complication recognizable by muscle cramps, abdominal pain, wheezing, and a feeling of of extreme weakness and malaise.
Warnings It is important to know that:
Pregnancy and breastfeeding
- Tell your doctor if you are, think you may be or plan to become pregnant. During pregnancy, diabetes must be treated with insulin. If during treatment with SLOWMET you discover that you are pregnant, consult your doctor so that he can modify your treatment.
- You should not take SLOWMET if you are breast-feeding or planning to breast-feed your baby.
- Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
- Taking SLOWMET does not affect the ability to drive and use machines. However, there is an increased risk of low blood sugar levels if SLOWMET is taken with other diabetes medicines (sulphonylureas, insulin, repaglinide). This can cause dizziness and fainting Do not drive or use machines unless you are sure you do not experience these symptoms.
Dose, Method and Time of Administration How to use Slowmet: Posology
Always take SLOWMET exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
The tablets should be swallowed with a glass of water in a single dose with the evening meal. If your blood glucose is not controlled, you may be prescribed two daily doses with meals. Follow your doctor's instructions carefully. The usual doses are listed below:
The usual starting dose is one SLOWMET 500 mg tablet once a day.
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. The maximum recommended dose is 4 SLOWMET 500 mg tablets per day.
Dose increases should be 500 mg every 10-15 days, up to a maximum of 2000 mg per day with the evening meal. If glycemic control is not achieved with SLOWMET 2000 mg in a single daily dose, treatment with SLOWMET 1000 mg, twice daily, taken with food should be considered. If glycemic control is still not achieved, patients should be switched to treatment with standard metformin tablets, up to the maximum dose of 3000 mg per day.
In patients already being treated with metformin tablets, the starting dose of SLOWMET should be equivalent to the daily dose of immediate-release metformin. Switching to SLOWMET is not recommended in patients already being treated with metformin at doses above 2000 mg per day.
In case of switching from another antidiabetic drug: discontinue the previous drug and start with SLOWMET at the dose indicated above.
SLOWMET 750 mg and SLOWMET 1000 mg should be used in patients already treated with metformin tablets (prolonged or immediate release).
The dose of SLOWMET 750 mg or SLOWMET 1000 mg should be equivalent to the daily dose of metformin tablets (prolonged or immediate release) up to a maximum dose of 1500 mg or 2000 mg respectively, taken with the evening meal.
Combination with insulin
Metformin hydrochloride and insulin can be used in combination to improve blood glucose control. Metformin hydrochloride is given at the normal starting dose of SLOWMET 500 mg tablets once a day, while the insulin dose is adjusted based on the glycemia.
Senior citizens:
Due to the potential for decreased renal function in elderly subjects, metformin hydrochloride dosage should be adjusted based on renal function. A periodic evaluation of renal function is therefore necessary.
Continue to take these tablets for as long as your doctor has told you. This medicine is not recommended for children.
If you forget to take SLOWMET
If you forget to take a tablet, you can take it as soon as you remember, unless the next dose is due soon. Do not take a double dose to make up for a forgotten dose. opportune moment.
If you stop using SLOWMET
If you stop taking SLOWMET without consulting your doctor, you should be aware that an uncontrolled rise in blood sugar may occur. Late symptoms of diabetes such as eye, kidney and vascular damage may occur.
If you go to another doctor or hospital, tell your doctor or hospital staff what medicines you are taking. If you have any further questions on the use of this product, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Slowmet
If you (or someone else) swallow several tablets all at once, or if you think a child has swallowed the tablets, contact the nearest hospital emergency department or doctor immediately.
Side Effects What are the side effects of Slowmet
Like all medicines, SLOWMET can cause side effects, although not everybody gets them.
If you notice any of the effects listed below, contact the nearest hospital emergency department or your doctor immediately:
- If you experience symptoms including muscle cramps, stomach pain, shortness of breath and an extreme feeling of weakness and malaise: these symptoms may indicate lactic acidosis, a serious but very rare side effect of metformin.
The following side effects have been observed at the approximate frequencies indicated:
Very common (affects more than 1 in 10 people):
- Nausea (feeling sick).
- He retched.
- Diarrhea.
- Abdominal pain (stomach pain).
- Lack of appetite.
Common (affects less than 1 in 10 people but more than 1 in 100 people):
- Disturbances in the sense of taste.
Very rare (affects less than 1 in 10,000 people):
- Decreased levels of vitamin B12 in the blood. Over time this can lead to anemia, ulceration of the mouth or tongue, weakness or tremor of the legs.
- Redness and itching of the skin, hives.
- There have also been isolated reports of liver problems, including hepatitis.
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 out of the reach and sight of children.
Do not use this medicine after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of the month indicated.
No particular storage conditions.
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.
Deadline "> Other information
What SLOWMET contains
The active ingredient is metformin hydrochloride.
- 500 mg: Each prolonged-release tablet contains 500 mg metformin hydrochloride corresponding to 390 mg of metformin base.
- 750 mg: Each prolonged-release tablet contains 750 mg metformin hydrochloride corresponding to 585 mg of metformin base.
- 1000 mg: Each prolonged-release tablet contains 1000 mg metformin hydrochloride corresponding to 780 mg of metformin base.
List of excipients
- 500 mg: Carmellose sodium, Hypromellose 100.000cP, Hypromellose 5cP, Microcrystalline cellulose, Magnesium stearate, Purified water
- 750 mg: Carmellose sodium, Hypromellose 100.000cP, Magnesium stearate, Purified water
- 1000 mg: Carmellose sodium, Hypromellose 100.000cP, Magnesium stearate, Purified water
Description of SLOWMET appearance and contents of the package
SLOWMET is produced in the form of tablets in three different concentrations which can be identified by the inscription:
- 500 mg: white to off-white, capsule-shaped tablets with "500" engraved on one face
- 750 mg: White, capsule-shaped, biconvex tablets, engraved with "750" on one face
- 1000 mg: White to off-white, capsule-shaped tablets with "1000" engraved on one face.
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 -
SLOWMET LONG-RELEASE TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
500 mg: Each prolonged-release tablet contains 500 mg metformin hydrochloride corresponding to 390 mg of metformin base.
750 mg: Each prolonged-release tablet contains 750 mg metformin hydrochloride corresponding to 585 mg of metformin base.
1000 mg: Each prolonged-release tablet contains 1000 mg metformin hydrochloride corresponding to 780 mg of metformin base.
For the full list of excipients, see section 6.1 "List of excipients".
03.0 PHARMACEUTICAL FORM -
Prolonged-release tablets.
500 mg: White to off-white, capsule-shaped tablets with "500" engraved on one face.
750 mg: White, capsule-shaped, biconvex tablets, engraved with "750" on one face.
1000 mg: White to off-white, capsule-shaped tablets with "1000" engraved on one face.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Treatment of Type 2 diabetes mellitus in patients intolerant to effective doses of immediate-release metformin due to the occurrence of severe gastrointestinal side effects and in patients in whom the onset of these effects prevents the achievement of the optimal dose of metformin. SLOWMET may be used alone or in combination with other oral antidiabetics or with insulin.
04.2 Posology and method of administration -
Monotherapy and combination with other oral antidiabetic drugs
The usual starting dose is one SLOWMET 500 mg tablet once a day.
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. The maximum recommended dose is 4 SLOWMET 500 mg tablets per day.
Dose increases should be 500 mg every 10-15 days, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved with SLOWMET 2000 mg in a single daily dose, treatment with SLOWMET 1000 mg, twice daily, taken with food should be considered. If glycemic control is still not achieved, patients should be switched to treatment with standard metformin tablets, up to the maximum dose of 3000 mg per day.
In patients already being treated with metformin tablets, the starting dose of SLOWMET should be equivalent to the daily dose of immediate-release metformin. Switching to SLOWMET is not recommended in patients already being treated with metformin at doses above 2000 mg per day.
In the case of patients who intend to switch from another antidiabetic agent to SLOWMET: stop taking the other agent and start taking SLOWMET at the doses indicated above.
SLOWMET 750 mg and 1000 mg should be used in patients already being treated with metformin (prolonged or immediate release).
The dose of SLOWMET 750 mg or 1000 mg should correspond to the daily dose of metformin (prolonged or immediate release), up to a maximum dose of 1500 mg or 2000 mg respectively, taken with the evening meal.
Combination with insulin
Metformin and insulin can be used in combination to improve blood glucose control. Metformin is given at the normal starting dose of SLOWMET 500 mg tablets once a day, while the insulin dose is adjusted based on blood glucose.
In patients already being treated with metformin and combined insulin, the dose of SLOWMET 750 mg or 1000 mg should be equivalent to the daily dose of metformin tablets up to a maximum dose of 1500 mg or 2000 mg, respectively, taken with the evening meal, while the insulin dose is adjusted based on blood glucose.
Senior citizens
Due to the potential for decreased renal function in elderly subjects, metformin dosage should be adjusted based on renal function. Periodic monitoring of renal function is necessary (see section 4.4)
Children
In the absence of available data SLOWMET should not be used in children.
04.3 Contraindications -
• Hypersensitivity to metformin or to any of the excipients.
• Diabetic ketoacidosis, diabetic pre-coma.
• Renal failure or renal dysfunction (creatinine clearance
• Acute conditions potentially capable of altering renal function such as:
o dehydration,
o severe infection,
or shock,
or intravascular administration of iodinated contrast agents (see section 4.4 "Special warnings and precautions for" use ").
• Acute or chronic diseases that can cause tissue hypoxia such as:
o heart or respiratory failure,
o recent myocardial infarction,
or shock.
• Liver failure, acute alcohol intoxication, alcoholism.
• Breastfeeding (see section 4.6)
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. Reported cases of lactic acidosis in patients treated with metformin have occurred in particular 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 in the event of non-specific signs, such as muscle cramps associated with digestive disturbances, 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 and admit the patient immediately (see section 4.9).
Physicians should warn patients about the risk and symptoms of lactic acidosis.
Kidney function Since metformin is excreted by the kidneys, creatinine clearance (which can be estimated from serum creatinine levels using the Cockcroft-Gault formula) 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. Particular attention should be paid to situations in which renal function may be compromised, for example when initiating antihypertensive therapy or therapy with diuretics and when initiating therapy with a non-steroidal anti-inflammatory drug (NSAID).
Administration of iodinated contrast agents
Intravascular administration of iodinated contrast media in radiological studies can lead to renal failure. This can lead to accumulation of metformin and increase the risk of lactic acidosis. administration not earlier than 48 hours after examination and only after checking whether renal function has returned to normal (see section 4.5).
Surgery
Metformin administration should be discontinued 48 hours prior to scheduled surgery under general, spinal or epidural anesthesia. Therapy should be resumed no earlier than 48 hours after surgery or before the patient has resumed oral feeding and only if renal function has been determined.
Other precautions
• All patients should continue their diet with regular distribution of carbohydrate intake throughout the day. Overweight patients should continue the low calorie diet.
• The laboratory tests normally required in cases of diabetes should be performed regularly.
• Taking metformin alone never causes hypoglycaemia, although caution is advised when used in combination with insulin or other oral antidiabetics (eg sulfonylureas or meglitinides).
• Parts of the tablet may be found in the faeces. It is recommended that patients be advised that this is normal.
04.5 Interactions with other medicinal products and other forms of interaction -
Concomitant use not recommended
Alcohol:
• Acute alcohol intoxication is associated with an increased risk of lactic acidosis, especially in cases of: fasting or malnutrition,
• liver failure.
Avoid the consumption of alcohol and drugs containing alcohol.
Iodized contrast agents
Intravascular administration of iodinated contrast agents may cause renal failure, resulting in accumulation of metformin and an increased risk of lactic acidosis.
Metformin should therefore be discontinued before or at the time of the examination, resuming administration no earlier than 48 hours after the examination and only after checking whether renal function has returned to normal. (see section 4.4).
Associations requiring precaution
Medicinal products with intrinsic hyperglycemic activity such as glucocorticoids (administered systemically and locally) and sympathomimetics. More frequent blood glucose checks may be necessary, especially at the start of treatment. If necessary, adjust the metformin dosage during therapy with the other drug.
ACE inhibitors, beta blockers and beta 2 agonists can reduce blood sugar. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and when it is stopped.
Diuretics, especially loop diuretics, may increase the risk of lactic acidosis due to their ability to reduce kidney function.
04.6 Pregnancy and breastfeeding -
Pregnancy:
Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with an increased risk of congenital anomalies and perinatal mortality.
A limited amount of data on the use of metformin in pregnant women did not indicate an increased risk of congenital abnormalities. Animal studies do not indicate harmful effects on pregnancy, embryonic or fetal development, parturition or postnatal development (see section 5.3 "Preclinical data. safety").
When the patient plans to become pregnant and during pregnancy itself, it is recommended not to treat diabetes with metformin but to use insulin to keep blood glucose as close to normal as possible in order to reduce the risk of fetal malformation.
Feeding time:
In lactating mice, metformin is excreted in milk. For the human species similar data are not available and it is therefore necessary to decide whether to discontinue breastfeeding or to discontinue metformin, considering the importance that the compound has for the mother.
Fertility
In rats, male or female fertility was not affected by metformin when administered at doses up to 600 mg / kg per day; this dose is approximately three times the maximum recommended daily dose in humans, calculated on the basis of the body surface area.
04.7 Effects on ability to drive and use machines -
Metformin alone does not cause hypoglycaemia, so it has no effect on the ability to drive or use machines. However, patients should be advised of the risk of hypoglycaemia when metformin is used in combination with other antidiabetic drugs (sulfonylureas, insulin or meglitinides).
04.8 Undesirable effects -
In post-marketing and clinical trial data, adverse reactions to SLOWMET were similar in nature and severity to those seen with immediate-release metformin.
The following side effects can occur during treatment with metformin.
Their frequency is defined as follows: very common: ≥1 / 10; common ≥1 / 100,
Nervous system disorders:
Common:
§ Changes in taste.
Gastrointestinal disorders:
§ Very common: gastrointestinal disturbances such as nausea, vomiting, diarrhea, abdominal pain and loss of appetite. These side effects occur more frequently during initiation of therapy and resolve spontaneously in most cases.
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. It is recommended that this etiology be considered in patients with megaloblastic anemia.
Hepatobiliary disorders: Very rare:
§ Isolated cases of liver function test abnormalities or hepatitis that have resolved following discontinuation of metformin treatment.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "Italian Medicines Agency Website: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
Hypoglycaemia has not been observed with metformin doses up to 85 g, although lactic acidosis has developed in such circumstances. Heavy metformin overdoses or concomitant risks may lead to lactic acidosis. Lactic acidosis is a medical emergency and must be treated in a hospital. The most effective method of eliminating lactate and metformin is hemodialysis.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: oral antidiabetics.
ATC code: A10BA02.
Metformin 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 can act through 3 mechanisms:
1. reduction of hepatic glucose production through inhibition of gluconeogenesis and glycogenolysis
2. in the muscles, increasing the sensitivity to insulin, improving the absorption and use of peripheral glucose
3. and delaying intestinal absorption of glucose.
Metformin stimulates intracellular glycogenosynthesis by acting on glycogen synthetase.
Metformin increases the transport capacity of all types of membrane glucose transporters (GLUT).
In humans, regardless of its action on glycaemia, metformin has favorable effects on lipid metabolism. This phenomenon has been demonstrated in controlled medium- and long-term clinical studies at therapeutic doses: metformin 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 in overweight patients treated with metformin after dietary failure alone demonstrated the following:
A significant reduction in the absolute risk of diabetes-related complications in the metformin group (29.8 events / 1000 patient years) compared to the diet alone (43.3 events / 1000 patient years), p = 0.0023, and compared to the monotherapy groups with insulin and sulfonylureas (40.1 events / 1000 patient years), p = 0.0034.
A significant reduction in the absolute risk of diabetes-related mortality: metformin 7.5 events / 1000 patient years, diet alone 12.7 events / 1000 patient years, p = 0.017;
A significant reduction in the absolute risk of overall mortality: metformin 13.5 events / 1000 patient-years versus diet alone 20.6 events / 1000 patient-years (p = 0.011), and versus insulin and sulfonylurea monotherapy groups 18.9 events / 1000 years patient (p = 0.021);
A significant reduction in the absolute risk of myocardial infarction: metformin 11 events / 1000 patient years, diet alone 18 events / 1000 patient years (p = 0.01).
For metformin used as second-line therapy in combination with a sulphonylurea, no benefit was seen in the clinical outcome.
In cases of type 1 diabetes, the combination of metformin and insulin has been used on selected patients but the clinical benefit of this combination has not been formally determined.
05.2 "Pharmacokinetic properties -
Absorption
After an oral dose of prolonged-release tablets, the absorption of metformin is significantly delayed, compared with immediate-release tablets, with a Tmax at 7 hours (the Tmax for immediate-release tablets is reached in 2.5 hours).
In steady state, similar to the immediate release formulations, C max and AUC not increased in proportion to the administered dose, the AUC after a single administration of 2000 mg prolonged-release metformin tablets is similar to that observed after administration of 1000 mg. of immediate-release metformin twice daily.
Subjective variability of C max and AUC of prolonged-release metformin is comparable to that observed for immediate-release tablets.
When the prolonged-release tablets are administered in the fasted state, the AUC is decreased by 30% (C max and T max both remain unchanged)
The absorption of prolonged-release metformin is hardly affected by the composition of the meal.
No accumulation was observed after repeated administration of up to 2000 mg of metformin prolonged-release tablets
After a single oral administration of 1500 mg of SLOWMET 750 mg, the mean peak plasma concentration of 1214 ng / ml is achieved at a mean of 5 hours (range 4 to 10 hours)
SLOWMET 1000 mg is bioequivalent to SLOWMET 500 mg at the dose of 1000 mg, relative to C max and AUC in fasting and post-eating healthy subjects.
When 1000 mg prolonged-release tablets are administered after eating, the AUC increases by 77% (C max is increased by 26% and T max is slightly prolonged to 1 hour)
Distribution
Plasma protein binding is negligible. Metformin 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 volume of distribution (Vd) is between 63 and 276 L.
Metabolism
Metformin is secreted unchanged in the urine. No metabolites have been identified in humans.
Elimination
The renal clearance index of metformin is> 400 mL / min: this indicates that metformin 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 a prolonged elimination half-life and increased plasma metformin levels.
05.3 Preclinical safety data -
On the basis of conventional studies concerning pharmacology, safety, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproductive function, preclinical data show no particular hazard for humans.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
500 mg: sodium carmellose, hypromellose 100,000cp, hypromellose 5cP, microcrystalline cellulose, magnesium stearate, purified water.
750 mg: sodium carmellose, hypromellose 100,000cP, magnesium stearate, purified water.
1000 mg: sodium carmellose, hypromellose 100,000cP, magnesium stearate, purified water.
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 -
500 mg: PVC / PVDC Aluminum blister.
750 mg. PVC / PVDC Aluminum blister.
1000 mg: PVC / PVDC Aluminum blister.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
No special instructions.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
I.B.N. SAVIO S.r.l. - Via del Mare, 36 - 00071 Pomezia (RM)
Dealer for sale :
Itapharma S.r.l. - Via Ponte a Piglieri, 8 - 56121 Pisa
08.0 MARKETING AUTHORIZATION NUMBER -
"500 mg prolonged-release tablets" 30 tablets AIC 040629014
"500 mg prolonged release tablets" 60 tablets AIC 040629026
"750 mg prolonged-release tablets" 30 tablets AIC 040629038
"750 mg prolonged release tablets" 60 tablets AIC 040629040
"1000 mg prolonged release tablets" 30 tablets AIC 040629053
"1000 mg prolonged release tablets" 60 tablets AIC 040629065
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
19/10/2012
10.0 DATE OF REVISION OF THE TEXT -
June 2016
