METFONORM 500 mg Tabletki Powlekane

Publication in Official Gazette Part II No. 15 of 05.02.2013, in force from 06.02.2013
METFONORM 1000 mg film-coated tablets
METFONORM 850 mg film-coated tablets
METFONORM 500 mg film-coated tablets
Metformin hydrochloride
Pharmacotherapeutic category
Oral hypoglycemic agents.

Therapeutic indications
Treatment of type 2 diabetes mellitus, particularly in overweight patients, when diet and exercise alone are not sufficient
to achieve adequate glycemic control.
o In adults, METFONORM in dosages of 500 mg, 850 mg and 1000 mg can
be used as monotherapy or in combination with other oral antidiabetic drugs or with insulin.
o In children over 10 years of age and adolescents, METFONORM in
dosages of 500 mg, 850 mg and 1000 mg can be used as monotherapy or in
combination with insulin.
A reduction in diabetes complications has been demonstrated in overweight adult patients with type 2 diabetes treated with metformin as
first-line therapy after dietary regimen failure.

Contraindications

• Hypersensitivity to metformin hydrochloride or to any of the excipients.
• Diabetic ketoacidosis, pre-coma diabeticum.
• Renal insufficiency or renal dysfunction (creatinine clearance < 60 mL/min).
• Acute conditions with the possibility of altered renal function such as:
• dehydration,
• severe infection,
• shock,
• intravenous or intra-arterial administration of iodinated contrast agents.
• Acute or chronic diseases that may cause tissue hypoxia such as:
• heart or respiratory failure,
• recent myocardial infarction,
• shock.
• Hepatic insufficiency, acute alcohol intoxication, alcoholism.
• Breastfeeding.

Publication in Official Gazette Part II No. 15 of 05.02.2013, in force from 06.02.2013
Appropriate precautions for use

Lactic acidosis
Lactic acidosis is a rare but serious metabolic complication (high mortality rate in the absence of rapid treatment) that can occur following an
accumulation of metformin. Cases of lactic acidosis in patients treated with
metformin have been reported particularly in diabetic patients with
severe renal insufficiency. The incidence of lactic acidosis can and must be
reduced by evaluating other risk factors as well, such as uncontrolled diabetes, ketosis, prolonged fasting, excessive alcohol consumption,
hepatic insufficiency and any other conditions associated with hypoxia.
Diagnosis: Lactic acidosis is characterized by dyspnea with acidosis, abdominal pain and hypothermia followed by coma. Laboratory diagnostic tests
show a decrease in blood pH, plasma lactate levels
greater than 5 mmol/L, and an increase in the anion gap and the lactate/pyruvate ratio. In case of suspected metabolic acidosis, discontinue
metformin and hospitalize the patient immediately.

Renal function:
Metformin is excreted by the kidneys, therefore it is appropriate to determine serum creatinine levels before starting treatment and subsequently, at regular
intervals:

• at least once a year in patients with normal renal function,
• at least two-four times a year in patients with serum creatinine levels at the upper limit of normal and in the elderly. A decrease in renal function in the elderly is frequent and asymptomatic. Special attention should be paid to situations where renal function may be compromised, for example when starting antihypertensive therapy or diuretic therapy and when starting therapy with NSAIDs.

Administration of iodinated contrast agents
Intravascular administration of iodinated contrast agents in radiological studies can lead to renal insufficiency; it is therefore necessary to
interrupt metformin before or at the time of the examination, resuming
administration no earlier than 48 hours after the examination and only after verifying that renal function has returned to normal.

Surgery
The administration of metformin hydrochloride must be discontinued 48 hours
before scheduled surgery under general anesthesia and should normally
be resumed no earlier than 48 hours after the operation.
Children and adolescents:

Publication in Official Gazette Part II No. 15 of 05.02.2013, in force from 06.02.2013
The diagnosis of type 2 diabetes mellitus must be confirmed before
starting treatment with metformin.
No effects of metformin on growth and puberty have been found during controlled clinical trials lasting one year, but there is no long-term data on these
specific points. It is therefore recommended to carefully monitor the effect of metformin on these parameters in children treated
with metformin, especially in prepubertal children.
Children aged between 10 and 12 years:
Only 15 subjects aged between 10 and 12 years were included in the controlled clinical trials conducted in children and adolescents. Although the efficacy and
safety in children under 12 years of age did not differ from those reported for
older children, particular attention is recommended when
prescribing metformin to children aged between 10 and 12 years.

Other precautions:

• Patients should continue their diet, distributing carbohydrate intake regularly throughout the day. Overweight patients should continue a hypocaloric diet.
• Laboratory tests normally prescribed for diabetes should be performed regularly.
• Metformin alone never causes hypoglycemia, although caution is advised when used in combination with insulin or sulfonylureas.

Interactions

Combinations not recommended

Alcohol
Increased risk of lactic acidosis in acute alcohol intoxication,
especially in cases of:

• fasting or malnutrition,
• hepatic insufficiency. Avoid consumption of alcohol and drugs containing alcohol.

Iodinated contrast agents
Intravascular administration of iodinated contrast agents can cause
renal insufficiency, with consequent accumulation of metformin and risk of
lactic acidosis.
Metformin should therefore be discontinued before or at the time of the analysis,
resuming administration no earlier than 48 hours after the examination and only after
verifying that renal function has returned to normal.

Associations requiring caution

Glucocorticoids (systemic and local), beta-2-agonists and diureticshave
intrinsic hyperglycemic activity. Inform the patient and perform more frequent
blood glucose checks, especially at the beginning of treatment. If necessary,

Publication in Official Gazette Part II No. 15 of 05.02.2013, in force from 06.02.2013
adjust the dosage of the antidiabetic drug during therapy with the other
drug and upon discontinuation of the latter.
ACE inhibitorscan reduce blood glucose. If necessary, adjust the
dosage of the antidiabetic drug during therapy with the other drug and
upon discontinuation of the latter.
Inform your doctor or pharmacist if you have recently taken any other
medicines, even those without a prescription.

Special warnings

Pregnancy and breastfeeding
Currently, no relevant epidemiological data are available. Animal studies
do not indicate harmful effects regarding pregnancy, embryonic or fetal development, delivery or postnatal development.
When a patient is planning a pregnancy and during pregnancy
itself, diabetes should not be treated with metformin but insulin should be used to keep blood glucose as close to normal as possible, in order to
reduce the risk of fetal malformations associated with abnormal blood glucose levels.
In the lactating mouse, metformin is excreted in milk. No analogous data are available for
humans and therefore it is necessary to decide whether to discontinue breastfeeding or discontinue metformin, considering
the importance of the compound for the mother.
Ask your doctor or pharmacist for advice before taking any
medicines.

Ability to drive and operate machinery
METFONORM in monotherapy does not cause hypoglycemia, therefore it has no effects
on the ability to drive or operate machinery.
Patients should nevertheless be informed of the risk of hypoglycemia when
metformin is used in combination with other antidiabetic drugs
(sulfonylureas, insulin, repaglinide).

Dosage, method and time of administration

Adults:

Monotherapy and combination with other oral antidiabetic drugs

• Normally the initial dose is one METFONORM 500 mg or 850 mg tablet 2 or 3 times a day taken during or after meals.
• After 10-15 days the dose should be adjusted based on blood glucose levels. A gradual increase in dosage may improve gastrointestinal tolerability.

Publication in Official Gazette Part II No. 15 of 05.02.2013, in force from 06.02.2013
In patients taking a high dose of metformin (from 2 to 3 grams
per day), two METFONORM 500 mg tablets can be replaced
with one METFONORM 1000 mg tablet.
The maximum recommended dose of metformin is 3 g per day.

• In case of switching from another oral antidiabetic drug to metformin: discontinue the previous drug and start with metformin at the above dose.

Combination with insulin
Metformin and insulin can be used in combination to improve
blood glucose control. Metformin is administered
at the initial normal dose of one METFONORM 500 mg or 850 mg
tablet 2-3 times a day, while the dose of insulin is adjusted based on
blood glucose levels.

Elderly:due to the potential reduction in renal function in the elderly, the dosage of metformin must be adjusted based on
renal function. Therefore, regular assessment of renal function is necessary.

Children and adolescents:
Monotherapy and combination with insulin:
o METFONORM can be used in children over 10 years of age
and adolescents.
o Normally the initial dose is one 500 mg or 850 mg tablet
once a day, taken during or after meals.
o After 10-15 days the dose should be adjusted based on blood glucose
levels. A slow increase in dosage may improve gastrointestinal
tolerability. The maximum recommended dose of metformin is 2
g per day, taken in 2 or 3 separate doses.

Overdose
No cases of hypoglycemia have been observed with metformin dosages up to
85 g, although lactic acidosis has occurred in such circumstances. High overdoses
of metformin or concomitant risks of metformin can lead to lactic
acidosis. Lactic acidosis is a medical emergency and must be treated
in hospital. The most effective method for eliminating lactate and metformin is
hemodialysis.
In case of accidental ingestion of an excessive dose of METFONORM
immediately notify your doctor or go to the nearest hospital.

Undesirable effects
Like all medicines, METFONORM can cause side effects, although
not everyone gets them.

Publication in Official Gazette Part II No. 15 of 05.02.2013, in force from 06.02.2013
Some patients report the following side effects during therapy with
metformin:
More than 1 in 10 patients reports gastrointestinal disorders
such as:

• nausea,
• vomiting,
• diarrhea,
• abdominal pain,
• loss of appetite. These side effects occur more frequently during the start of therapy and resolve spontaneously in most cases. To prevent them, it is recommended to take metformin in 2 or 3 daily doses during or after meals. A slow increase in dosage can also improve gastrointestinal tolerability.

From 1 in 10 to 1 in 100 patients report:

• taste alterations.

Less than 1 in 10,000 patients report:

• skin reactions such as erythema, pruritus, urticaria,
• decreased absorption of vitamin B12 with decreased serum levels during long-term use of metformin,
• alterations in liver function tests or hepatitis that resolved after discontinuation of metformin treatment.

Less than 1 in 10,000 patients treated with metformin have
experienced a condition called lactic acidosis (excess of lactic acid
in the blood), particularly those with impaired kidney function. Symptoms include: feeling cold or unwell, severe nausea or vomiting, abdominal pain, unexplained weight loss or rapid breathing
(panting). If you experience any of these symptoms, stop taking
METFONORM and consult a doctor immediately.
undesirable effects.
If any of these side effects worsen, or if you notice any
inform your doctor or pharmacist.

Shelf life and storage.
Check the expiration date indicated on the packaging.
The expiration date refers to the product in intact packaging,
stored correctly.

Caution:do not use the medicine after this date.

Publication in the Official Gazette Part II No. 15 of 05.02.2013, effective from 06.02.2013
Medicines should not be disposed of via wastewater or household waste.
Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

Composition
Metfonorm 1000 mg film-coated tablets
One tablet contains:

Active ingredient
Metformin hydrochloride mg 1000.

Excipients
Hypromellose, povidone, magnesium stearate. Coating: hypromellose, macrogol
6000, titanium dioxide.

Metfonorm 850 mg film-coated tablets
One tablet contains:

Active ingredient
Metformin hydrochloride mg 850.

Excipients
Hypromellose, povidone, magnesium stearate. Coating: hypromellose,
macrogol 6000, titanium dioxide.

Metfonorm 500 mg film-coated tablets
One tablet contains:

Active ingredient
Metformin hydrochloride mg 500.

Excipients
Hypromellose, povidone, magnesium stearate. Coating: hypromellose, macrogol
6000, titanium dioxide.

Pharmaceutical form and content
METFONORM 1000 mg:film-coated tablets divisible in packs of
60 tablets .

METFONORM 850 mg:film-coated tablets in packs of 40
tablets .

METFONORM 500 mg:film-coated tablets in packs of 30
tablets .

Publication in the Official Gazette Part II No. 15 of 05.02.2013, effective from 06.02.2013
Marketing Authorisation Holder
ABIOGEN PHARMA S.p.A.
Via Meucci 36
Ospedaletto - PISA.

Manufacturer responsible for batch release
ABIOGEN PHARMA S.p.A.
Via Meucci, 36
Ospedaletto – Pisa

KEEP THE MEDICINE OUT OF THE REACH AND SIGHT OF
CHILDREN
February 2013