natgillin/translations-raw huggingface dataset:
ιανίε αναρπόκ ατσ ιατάτκανα υοπ α σάλκ ονέ ηφορροπα η οτ α ότσ οτ
If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation.
,
4.6.
20- 30%.
Pregnancy and lactation
όπα ςησόδ ησηγήροχ όπα αρετσΎ α οτά ήιγυ ατσ
To date, no relevant epidemiological data are available.
υοπίρεπ ιανίε
Metformin is excreted into milk in lactating rats.
ροφτε υοίκσιδ ησηγήροχ όπα αρετσύ ςηνί ροφτε ςητ ατητό ισεθαιδοιβ ητυλόπα Η ςερώ ιανίε ςησηφόρροπα ςονόρχ ςοτσιγέ ο α ότσ οτ όπα ςηνί ροφτε ςησόδ ησηγήροχ όπα αρετσΎ,
Similar data is not available in humans and a decision should be made whether to discontinue nursing or to discontinue metformin, taking into account the importance of the compound to the mother.
2, 5
4.7.
ησηφόρροπΑ:
Effects on ability to drive and to use machines
ίεθυεθηλαπε α ησίπε ιεχέ νεδ ύο σαυδνυσ υοτ ύοτυα ςοδρέκ όκινιλκ οτ άλλα ςίενεθσα
GLUCOPHAGE monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.
ςετητόιδι ςέκιτηνικοκα ραΦ
However, patients should be alerted to the risk of hypoglycaemia when metformin is used in combination with other antidiabetic agents (sulfonylureas, insulin, repaglinide).
5. 2.
4.8.
ςυονέ γελιπε εσ ίεθηιοπο ισηρχ ιεχέ ςηνίλυοσνι ιακ ςηνί ροφτε ςό σαυδνυσ ο ίεθυεθηλαπε ιεχέ νεδ α σελέτοπα όκινιλκ οτ ε άκιτεχσ ςοδρέκ.
- Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of
υοπύτ ητήβαιδ οτΣ οτ αίρυολυνοφλυοσ
appetite (> 10%) are very common: these occur most frequently during initiation of therapy and resolve spontaneously in most cases.
ε ό σαυδνυσ εσ αίεπαρεθ ασυούερετυεδ ςω ιατίειοπο ισηρχ υοπ ηνί ροφτε ητ αιΓ ονόρχ ςίενεθσα
A slow increase of the dose may also improve gastrointestinal tolerability.
ατνάβ υσ -
- Metallic taste (3%) is common
ονό ατιαίδ ονόρχ ςίενεθσα / 1000
- Mild erythema has been reported in some hypersensitive individuals.
ατνάβ υσ
The incidence of such
18
effects is regarded as very rare (< 0.01%) CPMP/4082/00
-
7/16
/ 1000
EMEA 2001
ηνί ροφτε υοίδρακου υοτ ςοτα γάρφ ε υονύδνικ υοτυλόπα υοτ ησωίε ήκιτνα ησ
- A decrease of vitamin B12 absorption with decrease of serum levels has been observed in patients
:
treated long -term with metformin and appears generally to be without clinical significance (< 0.01%).
ονόρχ ςίενεθσα
- Lactic acidosis (0.03 cases/1000 patient-years) is very rare (see 4.4.
ατνάβ υσ
Warnings and special
(p=0, 021); ηνίλυοσνι
precautions for use).
/ 1000
4.9.
18, 9
Overdose
ε ςαίεπαρεθονο ιακ ς ςαίρυολυνοφλυοσ ςηνέ σαυδνυσ νωδά ο νωτ ιτνανέ ιακ
Hypoglycaemia has not been seen with metformin doses of up to 85 g, although lactic acidosis has occurred in such circumstances.
(p=0, 011),
5.
ονόρχ ςίενεθσα
PHARMACOLOGICAL PROPERTIES
ατνάβ υσ / 1000
Pharmacodynamic properties
ονό ςατιαίδ ιτνανέ ονόρχ ςίενεθσα
It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
ατνάβ υσ
Metformin may act via 3 mechanisms:
13, 5
This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: metformin reduces total cholesterol, LDL cholesterol and triglyceride levels.
/ 1000
Clinical efficacy:
ηνί ροφτε ςατητό ισηνθ ςήκινεγ υονύδνικ υοτυλόπα υοτ ησωίε ήκιτνα ησ
- a significant reduction of the absolute risk of any diabetes-related complication in the metformin
ςίενεθσα
group (29.8 events/ 1000 patient -ye ars) versus diet alone (43.3 events/ 1000 patient-years), p=0.0023, and versus the combined sulfonylurea and insulin monotherapy groups (40.1 events/ 1000 patient-years), p=0.0034.
ονό ατιαίδ ονόρχ ςίενεθσα
- a significant reduction of the absolute risk of diabetes-related mortality: metformin
ονόρχ ςίενεθσα
7.5 events/1000 patient -ye ars, diet alone 12.7 events/ 1000 patient-years, p=0.017;
ατνάβ υσ
- a significant reduction of the absolute risk of overall mortality: metformin 13.5 events/
ονό ςατιαίδ ιτνανέ ονόρχ ςίενεθσα
1000 patient -ye ars versus diet alone 20.6 events/ 1000 patient-years (p=0.011), and versus the combined sulfonylurea and insulin monotherapy groups 18.9 events/ 1000 patient-years (p=0.021);
ςηνί ροφτε αδά ο νητσ -
- a significant reduction in the absolute risk of myocardial infarction: metformin 11 events/
ητήβαιδ αρετσύ
1000 patient-years, diet alone 18 events/ 1000 patient-years (p=0.01) For metformin used as second-line therapy, in combination with a sulfonylurea, benefit regarding clinical outcome has not been shown.
οτ ε ησέχσ ιεχέ υοπ ςήκολπιπε ετοπήδσαιο υονύδνικ υοτυλόπα υοτ ησωίε ήκιτνα ησ ιεξίεδ νυοχέ ονό ατιαίδ ε αίχυτοπα όπα ηνί ροφτε ε νακηθύεπαρεθ υοπ ςίενεθσα ςυοκρασύχαπ εσ νωτά σελετοπα νωτ ησυλάνα Η υοπύτ ητήβαιδ οτσ ςοτα ία υοτ ςηζόκυλγ ςητ υοχγέλε ύοκιτατνε 2.
Pharmacokinetic properties
:
8/16
,
EMEA 2001
-
Absorption:
υοτ ςολεφό ο σεθόρπορκα οτ ιεξίεδοπα ιεχέ ητέλε ηνέ ηιοποιαχυτ ήκιτυενχινα Η
Absolute bioavailability of a 500 mg or 850 mg metformin tablet is approximately 50-60% in healthy subjects.
νωίδιρεκυλγιρτ αδεπίπε ατ ιακ
After an oral dose, the non- absorbed fraction recovered in faeces was 20-30%.
ατητόκιτα σελετοπα ήκινιλΚ
After oral administration, metformin absorption is saturable and incomplete.
ηνίρετσηλοχ ητ ιακ ηνίρετσηλοχ ήκιλονυσ LDL
It is assumed that the pharmacokinetics of metformin absorption is non-linear.
ητ ιενώιε ηνί ροφτε η ςετέλε ςέκινιλκ ςε σεθόρπορκα ή ςε σεθσόρποσε ςενε όχγελε:
At the usual metformin doses and dosing schedules, steady state plasma concentrations are reached within 24 to 48 hours and are generally less than 1 µg/ml.
7
In controlled clinical trials, maximum metformin plasma levels (Cmax) did not exceed 4 µg/ml, even at maximum doses.
ΥΟΝΕΜΙΕΚ ΥΟΤ ΣΗΣΗΡ ΕΘΑΝΑ ΑΙΝΗΜΟΡΕΜΗ
Food decreases the extent and slightly delays the absorption of metformin.
10.
Distribution:
ΣΑΙΕ∆Α ΣΗΤ ΣΗΣ ΕΝΑΝΑ ΣΗΣΙΡΚΓΕ ΣΗΤ ΡΠ ΑΙΝΗΜΟΡΕΜΗ
Metformin partitions into erythrocytes.
ΣΑΙΡΟΦΟΛΚΥΚ ΣΑΙΕ∆Α ΙΟ ΣΟΜΘΙΡΑ
The blood peak is lower than the plasma peak and appears at approximately the same time.
ΣΑΙΡΟΦΟΛΚΥΚ ΣΑΙΕ∆Α ΣΗΤ ΣΟΧΟΤΑΚ
The red blood cells most likely represent a secondary compartment of distribution.
ησητίαπα ηρετίαιδι αί αΚ.
The mean Vd ranged between 63-276 L
7.
Metabolism:
ιατεζάιερχ νοσό φε ςηψιρρόπα ιακ ύο σιριεχ ςωεσήρχ ςείγηδΟ
No metabolites have been identified in humans.
’ (ητκέιρεπ υοτ άκιτατσυσ ιακ ησύΦ
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.
6. 5.
5.3.
. ηξαλύφ ητ άτακ ηξαλύφορπ ηρετίαιδι αί αΚ
Preclinical safety data
ςοτνόϊορπ υοτ ηξαλύφ νητ άτακ ςιεξάλυφορπ ςερετίαιδΙ
Preclinical data reveal no special hazard for humans based on conventional studies on safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity reproduction.
6. 4.
6.
αινόρχ 6. 3. νε∆
PHARMACEUTICAL PARTICULARS
5
6.1.
ςετητόταβ υσΑ
List of excipients
6. 2.
Tablet core:
οισήνγα όκιταετΣ ηνόδιβοΠ K 30 υοίκσιδ ςανήρυΠ:
Povidone K 30 magnesium stearate
νωχόδκε ςογολάταΚ
Hypromellose
6. 1.
6.2.
ΣΕΙΡΟΦΟΡΗΛΠ ΣΕΚΙΤΥΕΚΑΜΡΑΦ
Not applicable
6.
6.3.
5. 3.
Shelf-life
6. 5
5 years CPMP/4082/00 6.4.
ηνί ροφτε η ιτό ςατνονχίεδ
Special precautions for storage
> 400 ml/ mn,
9/16
ήλοβοπΑ
EMEA 2001
άιδιαπ εσ ιατίεγηροχ
No special precautions for storage.
4. 4).
6.5.
α οτά ανέ ωικιλΗ:
Nature and contents of the container
2- 3
6.6.
ατητόκιτκενα ήκιρετνεορτσαγ
Instructions for use, handling and disposal
όπα αρετσΎ
No special requirements
10
7.
ςετνογάραπ
MARKETING AUTHORISATION HOLDER
).
8.
οφαργάραπ επέλβ
MARKETING AUTHORISATION NUMBER(S)
,,
9.
ςιεξίεδνε ςέκιτυεπαρεΘ
DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION
4. 1.
10.
. οίκσιδ ονέ
DATE OF REVISION OF THE TEXT
υλακιπΕ 3.
CPMP/4082/00 1.
επέλβ αχοδκέ,
NAME OF THE MEDICINAL PRODUCT
αιΓ
10/16
662, 9 mg
EMEA 2001
850 mg
GLUCOPHAGE/GLUCOPHAGE FORTE/DIANBEN/RISIDON 850 mg film-coated tablet.
. οίκσιδ ονέ
QUALITATIVE AND QUANTITATIVE COMPOSITION
GLUCOPHAGE/ GLUCOPHAGE FORTE/ DIANBEN/ RISIDON 850 mg ΣΟΤΝΟΪΟΡΠ ΥΟΚΙΤΥΕΚΑΜΡΑΦ ΥΟΤ ΑΙΣΑΜΟΝΟ
Each film-coated tablet contains metformin hydrochloride 850 mg corresponding to metformin base 662,9 mg
ονό ιατεγάσιεναπε αν ιακ ςή ικοδ ςητ
For excipients, see 6.1.
υοτ
PHARMACEUTICAL FORM
αίγρυοτιελ ήκιρφεΝ:
Film-coated tablet
ςό σαληΘ
CLINICAL PARTICULARS
•
4.1.
, αίξηλπατακ
Therapeutic indications
υοίδρακου υοτ α γαρφ έ οταφσόρπ
Treatment of type 2 diabetes mellitus in adults, particularly in overweight patients, when dietary management and exercise alone does not result in adequate glycemic control.
ςωπό νώτσι νωτ αίξοπυ ιεσέλακορπ αν ίεροπ αίοπο η αιενέθσα αινόρχ ή αίεξΟ
GLUCOPH AGE/GLUCOPHAGE FORTE/DIANBEN/RISIDON may be used as monotherapy or in combination with other oral antidiabetic agents, or with insulin.
ησήρχ ητ άτακ ςιεξάλυφορπ ςερετίαιδι ιακ ςιεσήιοποδιεορπ).
Pharmacodynamic properties).
•
4.2.
ςέκιδιΕ
Posology and method of administration
α ή τ επέλβ νωσέ νώκιφαργαικσ νωχύοιδωι ησηγήροχ 4. 4 (
Monotherapy and combination with other oral antidiabetic agents
αίξηλπατακ ηξω ίολ αίε ιρδ ησωτάδυφα
- The usual starting dose is one tablet 2 or 3 times daily given during or after meals.
10
After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements.
ςιεξίεδνετνΑ
A slow increase of dose may improve gastrointestinal tolerability.
4. 3.
The maximum recommended dose of metformin is 3 g daily.
αρέτη ητ αιγ ςαίσυο ςητ αίσα ησ η ηψόπυ ιατενάβ αλ αν ιεπέρπ αθ. ςηνί ροφτε ςητ ήποκαιδ η ή ύο σαληθ υοτ ήποκαιδ η ιατεζίσαφοπα νατό ςώπενυσ ςυοπώρθνα ςυοτ,, αιγ ιατνεθίταιδ εδ αίεχιοτσ αιο όραΠ νωίαρυορα νωτνόζαληθ αλάγ οτσ ιατενίρκκεπα ηνί ροφτεΜ Η.
- If transfer from another oral antidiabetic agent is intended: discontinue the other agent and initiate
ςηζόκυλγ αδεπίπε
metformin at the dose indicated above.
άκιγολοισυφ η ε ιατνοέδνυσ υοπ νώισαλπσυδ νώκϊυρβ ε ςονυδνίκ ο ιατενώιε αν υονέ ιεκορπ αδεπίπε αρετόκιγολοισυφ νότανυδ οτ οσό εσ ςοτα ία υοτ ςηζόκυλγ νωδέπιπε νωτ ησηρήταιδ,
Combination with insulin Metformin and insulin may be used in combination therapy to achieve better blood glucose control.
ητ αιγ ιατίειοπο ισηρχ αν ιεπέρπ αθ ηνίλυοσνι η ςω ό ηνί ροφτε ε ιατεύεπαρεθ αν ιεπέρπ
Metformin is given at the usual starting dose of one tablet 2-3 times daily, while insulin dosage is adjusted on the basis of blood glucose measurements.
ητ ή ότεκοτ νοτ υούρβ ε υοτ ηξυτπάνα νητ ηνύσο υκγε νητ ε ησέχσ εσ ςιεσάρδιπε ςίεβαλβιπε
Elderly: due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function.
ύο σαληθ ιακ ςηνύσο
Regular assessment of renal function is necessary (see section 4.4).
υκγε αιεκράιδ ητ άτακ ησηγήροΧ υοτ ήποκαιδ ητ άτακ
In the absence of data, GLUCOPHAGE / GLUCOPHAGE FORTE / DIANBEN / RISIDON should not be used in children.
4. 6.
4.3.
ιακ οκα ράφ ολλά ε αίεπαρεθ ητ άτακ υοκά ραφ ύοκιτηβαιδιτνα υοτ αίγολοσοδ νητ ετσό ρασορπ ίετσαιερχ νΑ ςοτα ία υοτ ςηζόκυλγ αδεπίπε ατ νυοσήξυα αν ίεροπ
Contraindications • Hypersensitivity to metformin hydrochloride or to any of the excipients. • Diabetic ketoacidosis, diabetic pre-coma.
ΑΕΜ)
CPMP/4082/00
ACE (.
11/16
ιακ
EMEA 2001
άτακ υοκά ραφ ύοκιτηβαιδιτνα υοτ αίγολοσοδ
• Renal failure or renal dysfunction (e.g., serum creatinine levels > 135 µmol/L in males and > 110 µmol/L in females). • Acute conditions with the potential to alter renal function such as:
νητ ετσό ρασορπ
- - - -
ίετσαιερχ νΑ ςαίεπαρεθ ςητ ήχρα νητσ αρετίαιδι ςοτα ία υοτ ςηζόκυλγ ςητ ησηθύολοκαραπ
Dehydration, severe infection, shock, intravascular administration of iodinated contrast agents (see 4.4 Warnings and special precautions for use).
νυοχέ
Acute - - -
άκιτηρυοιδ ατ ιακ ςίελοτσανα τήβ ιο ίοδο ίοκιποτ ιακ 2
or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure, recent myocardial infarction, shock
ίοκιτα ητσυσ ήδιεοκιτροκοκυλγ αΤ),
• Hepatic insufficiency, acute alcohol intoxication, alcoholism • Lactation.
(
4.4.
ςησήρχ ςιεξάλυφορπ νύοτιαπα υοπ ίο σαυδνυΣ
Special warnings and special precautions for use
ήκιγολοισυφ
Lactic acidosis.
ίεθερβ ιακ αίγρυοτιελ ήκιρφεν η ίεθη ιτκεναπε ύοφα
Lactic acidosis is a rare, but serious (high mortality in the absence of prompt treatment), metabolic complication that can occur due to metformin accumulation.
ονό ιακ ησατέξε νητ άτε ςερώ ονό
Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic patients with significant renal failure.
ιατεγάσιεναπε αν ιακ ςησατέξε ςητ αιεκράιδ νητ άτακ ή νιρπ ιατετπόκαιδ αν ιεπέρπ αθ ηνί ροφτε Η ςησωέξο ςήκιτκαλαγ ονυδνίκ ιακ ςηνί ροφτε ησυερώσσυσ εσ ίεγηδο αίοπο η αιεκράπενα
The incidence of lactic acidosis can and should be reduced by assessing also other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.
.
Diagnosis:
ςαιεκράπενα ςήκιταπη
Lactic acidosis is characterised by acidotic dyspnea, abdominal pain and hypothermia followed by coma.
ύο σιτισοπυ ή ςαίετσην ησωτπίρεπ
Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/L, and an increased anion gap and lactate/pyruvate ratio.
εσ ςωίδι α υενπόνιο ε ησαίρητηληδ αίεξο νητ άτακ ςησωέξο ςήκιτκαλαγ ςονυδνίκ ςονέ ηξυΑ, α υενπόνιΟ ίο σαυδνυσ ιονε ώτσινυσ ηΜ
If metabolic acidosis is suspected, metformin should be discontinued and the patient should be hospitalised immediately (see section 4.9).
ςησαρδίπεληλλα ςέφρο ςελλά
Renal function:
ιακ ατνόϊορπ άκιτυεκα ραφ αλλά ε ςιεσάρδιπεληλλΑ ςεδί αφλυοσ ή ηνίλυοσνι ε ό σαυδνυσ εσ ιατίειοπο ισηρχ.
As metformin is excreted by the kidney, serum creatinine levels should be determined before initiating 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.
νατό ησενύσ ιατάτσινυσ ιτόνολο αί ιακυλγοπυ έτοπ ίελακορπ νεδ ςητ ηνό ηνί ροφτε Η
Decreased renal function in elderly subjects is frequent and asymptomatic.
αν ιεπέρπ αθ ητήβαιδ υοτ ησηθύολοκαραπ αιγ ςέ ικοδ ςέκαιρητσαγρε ςενέ σιθηνυσ ιΟ ςαιεγρένε ύο σιροιρεπ ατιαίδ νητ
Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with an NSAID.
ςιεξάλυφορπ ςελλΆ ήκιγρυοριεΧ
Administration of iodinated contrast agent As the intravascular administration of iodinated contrast materials in radiologic studies can lead to renal failure, metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
νωέροφατε νώκιναρβ ε νωπύτ νωτ νωλό ςάροφατε ατητόνακι νητ ιενάξυα ηνί ροφτε Η
Surgery Metformin hydrochloride should be discontinued 48 hours before elective surgery with general anaesthesia and should not be usually resumed earlier than 48 hours afterwards.
υονόγοκυλγ
O ther precautions:
ςησάθνυσ ςητ ίπε ςατνώγρενε υονόγοκυλγ υοτ ησεθνύσ ήκιραττυκοδνε νητ ιερίεγειδ ηνί ροφτε Η
- All patients should continue their diet with a regular distribution of carbohydrate intake during
ςηζόκυλγ
the day.
ςηζόκυλγ ησήρχ ιακ ηψήλ ήκιρεφιρεπ
Overweight patients should continue their energy-restricted diet.
νητ ςατνονώιτλεβ ηνίλυοσνι νητσ αίσηθσιαυε νητ ςατνονάξυα ςυ ςυοτσ
- The usual laboratory tests for diabetes monitoring should be performed regularly.
ησυλόνεγο
CPMP/4082/00
(2)
12/16
(1)
EMEA 2001
αί ιακυλγοπυ ιεγάραπ νεδ αιεπένυσ
- Metformin alone never causes hypoglycaemia, although caution is advised when it is used in
ςό σιλοβατε ιακ ςόδο ήκιρετνεορτσαΓ
combination with insulin or sulfonylureas.
(A10BA02:
4.5.
ΑΚΙΤΗΒΑΙ∆ΙΤΝΑ ΑΝΕΜΟΝΑΒΜΑΛ ΣΟΤΑΜΟΤΣ ΥΟΤ ΟΠΑ
Interaction with other medicinal products and other forms of interaction Inadvisable combinations
ςετητόιδι ςέκι ανυδοκα ραΦ
Alcohol Increased risk of lactic acidosis in acute alcohol intoxication, particularly in case of:
ΣΕΤΗΤΟΙ∆Ι ΣΕΚΙΓΟΛΟΚΑΜΡΑΦ
- fasting or malnutrition,
5.
- hepatic insufficiency.
ήκιτκαλαγ ίεβ υσ ιεχέ ιακ να
Avoid consumption of alcohol and alcohol-containing medications.
ιρχέ ςηνί ροφτε ςιεσόδ ε αί ιακυλγοπυ ίεθηρηταραπ ιεχέ νε∆ 85 g,
Iodinated contrast agents Intravascular administration of iodinated contrast agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis.
ησήρχ
Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
ητ άτακ ςιεξάλυφορπ ςερετίαιδι ιακ ςιεσήιοποδιεορπ ςέκιδιΕ).
Associations requiring precautions for use Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity.
ςαίγολοσοδ ςητ ησαβρέπΥ
Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment.
4. 4. επέλβ αινάπσ ύλοπ ιανίε ονόρχ ςίενεθσα
If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation.
ησωέξο ήκιτκαλαγ Η
ACE-inhibitors may decrease the blood glucose levels.
νωιοτέτ ατητόνχυσ Η α οτά ατηθσίαυερεπυ ανέ σιρο εσ α ηθύρε οιπή ίεθρεφανα ιεχΈ
If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation
.
4.6.
ησύεγ ήκιλλατε Η
Pregnancy and lactation
ατητόκιτκενα ήκιρετνεορτσαγ
To date, no relevant epidemiological data are available.
ητ ιεσώιτλεβ αν ίεροπ ςησόδ ςητ ησηξύα ήγρα αιΜ α ύεγ οτ άτε ή ςοτα ύεγ υοτ αιεκράιδ ητ άτακ. αρέ η νητ ςιεσόδ ή εσ ιατενάβ αλ αν ηνί ροφτε η ιατάτσινυσ ατα ώτπ υσ άκιρετνεορτσαγ ατ
Animal studies do not indicate harmful effects with respect to pregnancy, embryonal or foetal development, parturition or postnatal development (see also section 5.3) When the patient plans to become pregnant and during pregnancy, diabetes should not be treated with metformin but insulin should be used to maintain blood glucose levels as close to normal as possible in order to lower the risk of foetal malformations associated with abnormal blood glucose levels.
ςηξερό ςητ:
Metformin is excreted into milk in lactating rats.
4. 8.
4.7.
οιδίνιλγαπερ ηνίλυοσνι
Effects on ability to drive and to use machines
, ςεδί αφλυοσ ςετνογάραπ ςύοκιτηβαιδιτνα ςυολλά ε ό σαυδνυσ εσ ιατίειοπο ισηρχ ηνί ροφτε (
GLUCOPHAGE / GLUCOPHAGE FORTE / DIANBEN / RISIDON monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.
η νατό ςαί ιακυλγοπυ ονυδνίκ νοτσ νώνεθσα νωτ ήχοσορπ η ιατάτσιφε αν ιεπέρπ αθ οσότσ νώναχη ησήρχ ητ ή νωτά ηχο ςησηγήδο ατητόνακι νητ ιεζάερηπε νεδ αιεπένυσ άτακ ιακ αί ιακυλγοπυ
However, patients should be alerted to the risk of hypoglycaemia when metformin is used in combination with other antidiabetic agents (sulfonylureas, insulin, repaglinide).
,
4.8.
ίελακορπ νεδ
Undesirable effects
GLUCOPHAGE/ GLUCOPHAGE FORTE/ DIANBEN/ RISIDON
- Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of
νώναχη ύο σιριεχ ιακ ςησηγήδο ατητόνακι νητσ ςιεσάρδιπΕ 12
appetite (> 10%) are very common: these occur most frequently during initiation of therapy and resolve spontaneously in most cases.
νοτσ ίετσιρωνγανα ιεχέ νεδ ςητίλοβατε ςανέναΚ αρύο ατσ ητωίολλανα ιατενίρκκεπα ηνί ροφτε Η
To prevent these gastrointestinal symptoms, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals.
ύξατε ιατενία υκ
A slow increase of the dose may also improve gastrointestinal tolerability.
οσέ οΤ ςή οναιδ ορώχ
- Metallic taste (3%) is common.
63- 276 L.
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ή οναι∆
EMEA 2001
υονόρχ ησατάραπ ιακ ηλύπ ακ νητ όπα ωτάκ ήχοιρεπ)
- Mild erythema has been reported in some hypersensitive individuals.
άτακ
The incidence of such
ησωίε α σάλπ
effects is regarded as very rare (< 0.01%)
οτσ ςησωρτνέκγυσ ςή ιτ ςητσιγέ ςητ
- A decrease of vitamin B12 absorption with decrease of serum levels has been observed in patients
όπα αρετσΎ ςηνί ροφτε ησηφόρροπα νητ ςώρφαλε ίερετσυθακ ιακ ό θαβ οτ ιενώιε ήφορτ Η. ςιεσόδ ςετσιγέ εσ ιακ α όκα
treated long-term with metformin and appears generally to be without clinical significance (< 0.01%).
ατ νασηβέρεπυ νεδ
- Lactic acidosis (0.03 cases/1000 patient-years) is very rare (see 4.4.
α σάλπ
Warnings and special
4 mcg/ ml,
precautions for use).
(Cmax)
4.9.
1 µg/ mL.
Overdose
ςέρεθατσ ιο ςαίγολοσοδ ατα άργορπ ανέ σιθηνυσ ατ ιακ ςηνί ροφτε ςιεσόδ ςενέ σιθηνυσ ςιτΣ, ήκι αργ η ιανίε ςηνί ροφτε ςησηφόρροπα ςητ ήκιτηνικοκα ραφ η ιτό ιατίερωεΘ. ςήλετα ιακ ήτσεροκ ιανίε ςηνί ροφτε ησηφόρροπα η α ότσ οτ όπα ςησόδ ησηγήροχ όπα αρετσΎ
Hypoglycaemia has not been seen with metformin doses of up to 85 g, although lactic acidosis has occurred in such circumstances.
αναρπόκ ατσ ιατάτκανα υοπ α σάλκ ονέ ηφορροπα η οτ α ότσ οτ 20- 30%.
High overdose or concomitant risks of metformin may lead to lactic acidosis.
όπα ςησόδ ησηγήροχ όπα αρετσΎ α οτά ήιγυ ατσ
Lactic acidosis is a medical emergency and must be treated in hospital.
υοπίρεπ ιανίε
The most effective method to remove lactate and metformin is haemodialysis.
νωτ ή νωτ
PHARMACOLOGICAL PROPERTIES
500 mg
5.1.
ςηνί
Pharmacodynamic properties
ησηφόρροπΑ:
ORAL ANTI-DIABETICS (A10BA02:
ίεθυεθηλαπε α ησίπε ιεχέ νεδ ύο σαυδνυσ υοτ ύοτυα ςοδρέκ όκινιλκ οτ άλλα ςίενεθσα
Gastrointestinal tract and metabolism) Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose.
ςετητόιδι ςέκιτηνικοκα ραΦ
It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
.
Metformin may act via 3 mechanisms:
ςυονέ γελιπε εσ ίεθηιοπο ισηρχ ιεχέ ςηνίλυοσνι ιακ ςηνί ροφτε ςό σαυδνυσ ο ίεθυεθηλαπε ιεχένεδ α σελέτοπα όκινιλκ οτ ε άκιτεχσ ςοδρέκ.
(1) reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis (2) in muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and utilisation (3) and delay of intestinal glucose absorption.
υοπύτ ητήβαιδ οτΣ οτ αίρυολυνοφλυοσ
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.
ε ό σαυδνυσ εσ αίεπαρεθ ασυούερετυεδ ςω ιατίειοπο ισηρχ υοπ ηνί ροφτε ητ αιΓ ονόρχ ςίενεθσα
Metformin increases the transport capacity of all types of membrane glucose transporters (GLUT).
ονό ατιαίδ ονόρχ ςίενεθσα / 1000
In humans, independently of its action on glycaemia, metformin has favorable effects on lipid metabolism.
ατνάβ υσ
Clinical efficacy:
ηνί ροφτε υοίδρακου υοτ ςοτα γάρφ ε υονύδνικ υοτυλόπα υοτ ησωίε ήκιτνα ησ
The prospective randomised (UKPDS) study has established the long -term benefit of intensive blood glucose control in type 2 di abetes.
ονόρχ ςίενεθσα
- a significant reduction of the absolute risk of any diabetes-related complication in the metformin
ηνίλυοσνι ε ςαίεπαρεθονο ιακ ςαίρυολυνοφλυοσ ςηνέ σαυδνυσ νωδά ο νωτ ιτνανέ ιακ ονόρχ ςίενεθσα
group (29.8 events/ 1000 patient-years) versus diet alone (43.3 events/ 1000 patient-years), p=0.0023, and versus the combined sulfonylurea and insulin monotherapy groups (40.1 events/ 1000 patient-years), p=0.0034.
ονό ςατιαίδ ιτνανέ ονόρχ ςίενεθσα
- a significant reduction of the absolute risk of diabetes-related mortality: metformin
1000
7.5 events/ 1000 patient-years, diet alone12.7 events/ 1000 patient-years, p=0.017;
/ 13, 5 ηνί ροφτε ςατητό ισηνθ ςήκινεγ υονύδνικ υοτυλόπα υοτ ησωίε ήκιτνα ησ
- a significant reduction of the absolute risk of overall mortality: metform in 13.5 events/
ςίενεθσα
1000 patient-years versus diet alone 20.6 events/ 1000 patient-years (p=0.011), and versus the combined sulfonylurea and insulin monotherapy groups 18.9 events/ 1000 patient-years, (p=0.021);
ητήβαιδ οτ ε ησέχσ ιεχέ υοπ ςατητό ισηνθ υονύδνικ υοτυλόπα υοτ ησωίε ήκιτνα ησ - ςίενεθσα
- a significant reduction in the absolute risk of myocardial infarction: metformin 11 events/
οτ ε ησέχσ ιεχέ υοπ ςήκολπιπε ετοπήδσαιο υονύδνικ υοτυλόπα υοτ ησωίε ήκιτνα ησ ιεξίεδ νυοχέ ονό ατιαίδ ε αίχυτοπα όπα ηνί ροφτε ε νακηθύεπαρεθ υοπ ςίενεθσα ςυοκρασύχαπ εσ νωτά σελετοπα νωτ ησυλάνα Η υοπύτ ητήβαιδ οτσ ςοτα ία υοτ ςηζόκυλγ ςητ υοχγέλε ύοκιτατνε 2.
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