Mefonorm

Italy
Brand name Mefonorm
Form tablets, film-coated
Active substance / Dosage
METFORMIN HYDROCHLORIDE
Prescription type Prescription only
ATC code
A10BA02
Registration number 035215
Manufacturer ABIOGEN PHARMA S.P.A.

Publication in Official Gazette Part II No. 15 of 05.02.2013, effective 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 hypoglycaemic agents.
Therapeutic indications
Treatment of type 2 diabetes mellitus, particularly in overweight patients, when diet and physical exercise alone are insufficient to achieve adequate glycaemic control.

  • In adults, METFONORM in doses of 500 mg, 850 mg and 1000 mg may be used as monotherapy or in combination with other oral antidiabetic drugs or with insulin.
  • In children over 10 years of age and adolescents, METFONORM in doses of 500 mg, 850 mg and 1000 mg may be used as monotherapy or in combination with insulin.
    A reduction in diabetes-related complications has been demonstrated in overweight adult patients with type 2 diabetes treated with metformin as first-line therapy following failure of dietary management.
    Contraindications
  • Hypersensitivity to metformin hydrochloride or to any of the excipients.
  • Diabetic ketoacidosis, diabetic pre-coma.
  • Renal insufficiency or renal dysfunction (creatinine clearance < 60 mL/min).
  • Acute conditions with potential for 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:
  • cardiac or respiratory failure,
  • recent myocardial infarction,
  • shock.
  • Hepatic insufficiency, acute alcohol intoxication, alcoholism.
  • Breast-feeding.

Publication in Official Gazette Part II No. 15 of 05.02.2013, effective from 06.02.2013
Appropriate precautions for use
Lactic acidosis
Lactic acidosis is a rare but serious metabolic complication (high mortality rate if not promptly treated) that may occur due to accumulation of metformin. Reported cases of lactic acidosis in patients treated with metformin have occurred particularly in diabetic patients with severe renal insufficiency. The incidence of lactic acidosis can and must be reduced by assessing other associated risk factors such as uncontrolled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic insufficiency and any other conditions associated with hypoxia.
Diagnosis: Lactic acidosis is characterized by dyspnoea with acidosis, abdominal pain and hypothermia, followed by coma. Diagnostic laboratory tests show decreased blood pH, plasma lactate levels above 5 mmol/L, and increased anion gap and lactate/pyruvate ratio. In case of suspected metabolic acidosis, discontinue metformin and admit the patient immediately.
Renal function:
Metformin is excreted by the kidneys; therefore, serum creatinine levels should be determined before starting treatment and subsequently at regular intervals:

  • at least once a year 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. Decline in renal function in the elderly is common and asymptomatic. Special attention should be paid to situations that may impair renal function, for example when initiating antihypertensive therapy or treatment with diuretics, or when starting therapy with NSAIDs.

Administration of iodinated contrast agents
Intravascular administration of iodinated contrast agents in radiological procedures may lead to renal impairment; therefore, metformin must be discontinued before or at the time of the procedure, and treatment should not be resumed earlier than 48 hours after the procedure and only after confirming that renal function has returned to normal.
Surgery
Administration of metformin hydrochloride must be discontinued 48 hours before elective surgery under general anaesthesia and normally should not be restarted earlier than 48 hours after surgery.
Children and adolescents:
Publication in Official Gazette Part II No. 15 of 05.02.2013, effective from 06.02.2013
The diagnosis of type 2 diabetes mellitus must be confirmed before initiating treatment with metformin.
No effects of metformin on growth and puberty were observed during controlled clinical trials lasting one year, but long-term data on these specific aspects are not available. Therefore, careful follow-up of the effect of metformin on these parameters is recommended 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 controlled clinical trials conducted in children and adolescents. Although efficacy and safety in children under 12 years did not differ from those reported in older children, particular caution is recommended when prescribing metformin to children aged between 10 and 12 years.
Other precautions:

  • Patients should continue their prescribed diet, distributing carbohydrate intake evenly throughout the day. Overweight patients should continue a low-calorie diet.
  • Routine laboratory tests normally required in diabetes cases should be performed regularly.
  • Metformin alone never causes hypoglycaemia, 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 medications containing alcohol.

Iodinated contrast agents
Intravascular administration of iodinated contrast agents may cause renal impairment, resulting in metformin accumulation and risk of lactic acidosis.
Therefore, metformin should be discontinued before or at the time of the procedure, and treatment should not be resumed earlier than 48 hours after the procedure and only after confirming that renal function has returned to normal.
Associations requiring caution
Glucocorticoids (systemic and local), beta-2-agonists and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary,
Publication in Official Gazette Part II No. 15 of 05.02.2013, effective from 06.02.2013
adjust the dosage of the antidiabetic drug during concomitant therapy and upon discontinuation of the other drug.
ACE inhibitors may reduce blood glucose. If necessary, adjust the dosage of the antidiabetic drug during concomitant therapy and upon discontinuation of the other drug.
Inform your doctor or pharmacist if you have recently taken any other medicine, including those without a prescription.
Special warnings
Pregnancy and breast-feeding
Currently, no relevant epidemiological data are available. Animal studies do not indicate harmful effects regarding pregnancy, embryonic or foetal development, parturition or postnatal development.
When a patient plans pregnancy or during pregnancy itself, diabetes should not be treated with metformin; insulin should be used instead to maintain blood glucose as close to normal as possible, thereby reducing the risk of fetal malformations associated with abnormal glucose levels.
In lactating mice, metformin is excreted in milk. For humans, no similar data are available, and therefore a decision must be made whether to discontinue breast-feeding or discontinue metformin, taking into account the importance of the drug to the mother.
Consult your doctor or pharmacist before taking any medicine.
Ability to drive and use machines
METFONORM as monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or use machinery.
However, patients should be informed of the risk of hypoglycaemia when metformin is used in combination with other antidiabetic drugs (sulfonylureas, insulin, repaglinide).
Dosage, method and timing of administration
Adults:
Monotherapy and combination with other oral antidiabetic drugs

  • The usual initial dose is one tablet of METFONORM 500 mg or 850 mg two or three times daily, taken during or after meals.
  • After 10-15 days, the dose should be adjusted based on blood glucose levels. Gradual dose escalation may improve gastrointestinal tolerability.

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

  • When switching from another oral antidiabetic drug to metformin: discontinue the previous drug and start metformin at the dose indicated above.

Combination with insulin
Metformin and insulin may be used together to improve blood glucose control. Metformin is administered at the usual initial dose of one tablet of METFONORM 500 mg or 850 mg two to three times daily, while the insulin dose is adjusted based on blood glucose levels.
Elderly: due to the potential reduction in renal function in elderly subjects, the dosage of metformin should be adjusted according to renal function. Regular assessment of renal function is therefore required.
Children and adolescents:
Monotherapy and combination with insulin:

  • METFONORM may be used in children over 10 years of age and adolescents.
  • The usual initial dose is one tablet of 500 mg or 850 mg once daily, taken during or after meals.
  • After 10-15 days, the dose should be adjusted based on blood glucose levels. Slow dose escalation may improve gastrointestinal tolerability. The maximum recommended dose of metformin is 2 g per day, taken in two or three divided doses.
    Overdose
    Hypoglycaemia has not been observed with metformin doses up to 85 g, although lactic acidosis has occurred under such circumstances. Large overdoses of metformin or concomitant risk factors may lead to lactic acidosis. Lactic acidosis represents a medical emergency and requires hospital treatment. The most effective method for removing lactate and metformin is haemodialysis.
    In case of accidental ingestion of an excessive dose of METFONORM, contact a doctor immediately or go to the nearest hospital.
    Undesirable effects
    Like all medicines, METFONORM can cause undesirable effects, although not everyone experiences them.
    Publication in Official Gazette Part II No. 15 of 05.02.2013, effective from 06.02.2013
    Some patients report the following undesirable effects during treatment with metformin:
    More than 1 in 10 patients report gastrointestinal disorders such as:
  • nausea,
  • vomiting,
  • diarrhoea,
  • abdominal pain,
  • loss of appetite. These undesirable effects occur more frequently at the beginning of therapy and resolve spontaneously in most cases. To prevent them, it is recommended to take metformin in two or three divided daily doses during or after meals. Slow dose escalation may also improve gastrointestinal tolerability.

Between 1 in 10 and 1 in 100 patients report:

  • taste disturbances.

Less than 1 in 10,000 patients report:

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

Less than 1 in 10,000 patients treated with metformin have experienced a condition called lactic acidosis (excess lactic acid in the blood), particularly those with impaired renal function. Symptoms include: feeling cold or unwell, severe nausea or vomiting, abdominal pain, unexplained weight loss or rapid breathing (panting). If any of these symptoms occur, stop taking METFONORM and consult a doctor immediately.
Following the instructions in this leaflet reduces the risk of undesirable effects.
If any of the undesirable effects worsen, or if you notice any undesirable effects not listed in this leaflet, inform your doctor or pharmacist.
Expiry date and storage
Check the expiry date stated on the packaging.
The expiry date refers to the product in intact packaging, correctly stored.
Caution: do not use the medicine after this date.
Publication in 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 no longer used. This will help protect the environment.
Composition
Metfonorm 1000 mg film-coated tablets
One tablet contains:
Active substance
Metformin hydrochloride 1000 mg.
Excipients
Hypromellose, povidone, magnesium stearate. Coating: hypromellose, macrogol 6000, titanium dioxide.
Metfonorm 850 mg film-coated tablets
One tablet contains:
Active substance
Metformin hydrochloride 850 mg.
Excipients
Hypromellose, povidone, magnesium stearate. Coating: hypromellose, macrogol 6000, titanium dioxide.
Metfonorm 500 mg film-coated tablets
One tablet contains:
Active substance
Metformin hydrochloride 500 mg.
Excipients
Hypromellose, povidone, magnesium stearate. Coating: hypromellose, macrogol 6000, titanium dioxide.
Pharmaceutical form and contents
METFONORM 1000 mg: film-coated tablets, divisible, pack size of 60 tablets.
METFONORM 850 mg: film-coated tablets, pack size of 40 tablets.
METFONORM 500 mg: film-coated tablets, pack size of 30 tablets.
Publication in Official Gazette Part II No. 15 of 05.02.2013, effective from 06.02.2013
Marketing Authorization Holder
ABIOGEN PHARMA S.p.A.
Via Meucci 36
Ospedaletto - PISA.
Responsible person for batch release
ABIOGEN PHARMA S.p.A.
Via Meucci, 36
Ospedaletto – Pisa
KEEP THIS MEDICINE OUT OF THE SIGHT AND REACH OF CHILDREN
February 2013