Gliconorm

Patient Information Leaflet

GLICONORM 5mg + 500mg Film-coated Tablets

GLIBENCLAMIDE + METFORMIN HYDROCHLORIDE
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What GLICONORM is and what it is used for
2. What you need to know before taking GLICONORM
3. How to take GLICONORM
4. Possible side effects
5. How to store GLICONORM
6. Contents of the pack and other information

1. What GLICONORM is and what it is used for

GLICONORM is an oral antihyperglycaemic medicinal product (lowers blood glucose levels) containing two active substances:

• metformin hydrochloride (belonging to the class of biguanides)
• glibenclamide (belonging to the class of sulphonylureas).

GLICONORM is indicated in adults for the treatment of non-insulin-dependent diabetes mellitus
(also known as type 2 diabetes), non-ketoacidotic (i.e. not associated with increased levels of substances
called "ketone bodies" in urine or blood), when glucose levels are not controlled by diet alone or by
combination therapy with diet and sulphonylureas (medicinal products used to treat diabetes).

2. What you should know before taking GLICONORM

Do not take GLICONORM

• if you are allergic to metformin, glibenclamide, or any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to other medicines containing substances similar to metformin;
• if you have latent diabetes (not yet manifested) or suspect you may have diabetes;
• if you have gestational diabetes (diabetes occurring during pregnancy);
• if you have insulin-dependent diabetes (type requiring insulin administration);
• if you have uncontrolled diabetes associated, for example, with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see below “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called “ketone bodies” accumulate in the blood and may lead to diabetic pre-coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, and breath with an unusually fruity odour;
• if you suffer from loss of consciousness or a sensation of losing consciousness due to diabetes (diabetic coma or pre-coma);
• if you have severe liver problems (hepatic insufficiency);
• if you have severely reduced kidney function;
• if you are taking diuretic medicines (to increase urine production) or antihypertensive medicines (to lower blood pressure) that could affect your kidney function;
• if you are scheduled for a test to evaluate kidney function (intravenous urography);
• if you have diseases that may alter how your kidneys work (e.g. if you have lost a lot of fluids, if you have a severe ongoing infection, or if you suffer from reduced blood flow to all organs (shock));
• if you have severe heart problems (heart failure, recent heart attack, shock);
• if you have severe respiratory problems (respiratory failure);
• if you have an adrenal gland disease (glands located above the kidneys);
• if you abuse alcohol or have recently abused it (see section “GLICONORM with food and alcohol”);
• if you eat very little (very low-calorie diets) or especially if you are fasting (see section “GLICONORM with food and alcohol”);
• if you have severe neuromuscular diseases (dystrophic);
• if you have severe acute bleeding;
• if you have reduced blood flow to all organs (shock);
• if you have localized tissue-destructive processes leading to tissue death (gangrene);
• if you have undergone or are scheduled to undergo surgery, do not take GLICONORM within two days before or after the procedure;
• if you are pregnant;
• if you are breastfeeding;
• if you are scheduled to undergo imaging tests involving injection of iodine-containing contrast agents (see section “Other medicines and GLICONORM”).

Warnings and precautions
Talk to your doctor or pharmacist before taking GLICONORM.
Taking GLICONORM may expose you to an increased risk of life-threatening heart and blood vessel diseases (cardiovascular mortality), especially if you also have heart artery disorders (coronary diseases), compared to treatment with other diabetes medicines such as metformin or gliclazide.
Patients aged 65 years or older are particularly sensitive to the hypoglycaemic effect of glibenclamide and are therefore at higher risk of hypoglycaemia. In elderly patients, low blood sugar levels may be somewhat difficult to recognize. The initial and maintenance doses of glibenclamide must be carefully determined by your treating physician to avoid hypoglycaemic reactions.

Risk of lactic acidosis
GLICONORM may cause a very rare but very serious side effect called lactic acidosis, particularly if the kidneys are not functioning properly. The risk of developing lactic acidosis is higher in the presence of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see below for further information), liver problems, or any other medical condition characterized by reduced oxygen supply to part of the body (such as severe heart disease).
If you have any of the medical conditions listed above, consult your doctor for further instructions. Your doctor will frequently monitor your health through tests to assess whether you have factors that may favour the onset of lactic acidosis, especially:

• if you are over 60 years old
• if you have severe kidney disease
• if you have ketone bodies in your blood, a condition also known as acetone (ketosis)
• if you suffer from a disease causing oxygen deficiency in the body
• if you have liver disease
• if you have heart or lung disease
• if you abuse alcohol
• if you are fasting for prolonged periods
• if you are being treated with diuretic medicines (used to increase urine production)
• if you have stomach or intestinal problems

Temporarily stop taking GLICONORM if you develop a medical condition that may be associated with dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, heat exposure, or if you are drinking less fluid than normal. Consult your doctor for further instructions.

If you experience any of the symptoms of lactic acidosis, stop taking GLICONORM and contact your doctor or the nearest hospital immediately, because lactic acidosis can lead to coma.
Symptoms of lactic acidosis include:

• vomiting
• stomach ache (abdominal pain)
• muscle cramps
• a general feeling of discomfort associated with severe fatigue
• difficulty breathing
• reduced body temperature and slower heartbeat

Lactic acidosis is a medical emergency and must be treated in hospital.
Contact your doctor immediately for further instructions if:

• you know you have a hereditary genetic disease affecting mitochondria (cellular components that produce energy), such as MELAS syndrome (Mitochondrial Encephalopathy, myopathy, Lactic Acidosis and Stroke-like episodes, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) or Maternally Inherited Diabetes and Deafness (MIDD);
• you experience any of the following symptoms after starting metformin: seizures, reduced cognitive abilities, difficulty with body movements, symptoms indicating nerve damage (e.g. pain or numbness), headache, or hearing loss.

If you are scheduled for major surgery, you must stop taking GLICONORM during and for a certain period after the procedure. Your doctor will decide when to stop and when to restart treatment with GLICONORM.

During treatment with GLICONORM, your doctor will monitor your kidney function at least once a year, or more frequently if you are elderly and/or if kidney function worsens.
Also inform your doctor:

• if you experience symptoms of hypoglycaemia (low blood sugar levels) such as headache, irritability, difficulty concentrating, sleep disturbances, tremors, nausea, excessive sweating, or hunger. If you experience these symptoms, take carbohydrates (sugars) and INFORM YOUR DOCTOR IMMEDIATELY: you may need blood tests, temporary discontinuation of therapy, or hospitalization to bring your blood glucose back under control.

Symptoms of hypoglycaemia may occur, although rarely, especially:

• if you are weakened
• if you are elderly
• if you perform unusual physical exertion
• if you have irregular eating habits
• if you consume alcoholic beverages
• if you have kidney or liver problems

Inform your doctor also in case of trauma, surgical procedures, infectious or febrile illnesses. Your doctor might temporarily prescribe insulin therapy for better control of blood sugar levels.

Also inform your doctor:

• if you have a deficiency of an enzyme called glucose-6-phosphate dehydrogenase (G6PD). In this case, your doctor will administer this medicine cautiously or recommend another medicine to avoid the risk of haemolytic anaemia (a disease of red blood cells, a type of blood cell);
• if you have a blood disorder called megaloblastic anaemia, caused by reduced absorption of vitamin B (see section 4. “Possible side effects”).

Continue following the diet prescribed by your doctor and undergo regular blood tests even during treatment with GLICONORM.

Children and adolescents
Do not give GLICONORM to children or adolescents, as it is not indicated for them.

Other medicines and GLICONORM
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
If you are scheduled to receive an injection of iodinated contrast medium into the bloodstream, for example for an X-ray, you must stop taking GLICONORM before or during the injection. Your doctor will decide when to stop and when to restart treatment with GLICONORM.
In any case, inform your doctor if you are taking, have recently taken, or might take any other medicines. You may need to check your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of GLICONORM. It is particularly important to mention the following:

• the following medicines that may increase the effect of GLICONORM:

  • dicoumarol and derivatives (medicines to make blood less likely to clot)
  • monoamine oxidase inhibitors (medicines for treating depression)
  • antibiotics (medicines for treating infections, such as sulfonamides, quinolones (especially fluoroquinolones such as gatifloxacin, ciprofloxacin, etc.) and chloramphenicol)
  • phenylbutazone and derivatives (medicines for treating inflammation and pain)
  • cyclophosphamide (medicine for treating tumours)
  • probenecid (medicine for treating gout, a disease causing joint inflammation and pain)
  • fibrates (medicines for lowering cholesterol)
  • pheniramidol (medicine for treating pain)
  • salicylates (medicines for treating inflammation)
  • oral miconazole (medicine used to treat fungal infections)
  • sulfinpyrazone (medicine to prevent heart attacks)
  • perhexiline (medicine for treating heart diseases)
  • medicines containing alcohol (see section “GLICONORM with food and alcohol”)

• the following medicines that may decrease the effect of GLICONORM:

  • adrenaline (medicine used to treat severe allergic reactions)
  • corticosteroids (medicines used to treat inflammation)
  • oral contraceptives (the pill)
  • thiazide diuretics (medicines used to increase urine production)
  • diazoxide (medicine used to lower blood pressure)
  • phenothiazine derivatives (tranquillizing medicines)
  • phenytoin and barbiturates (medicines used to treat epilepsy)
  • H₂-receptor antagonists (medicines used in the treatment of ulcers, stomach perforations)
  • ß-blockers (medicines used to treat high blood pressure)
  • clonidine (medicine used to lower blood pressure)
  • guanethidine or reserpine (medicines used to lower blood pressure or treat mental disorders)
  • iodine-containing contrast agents

Also inform your doctor if you are taking the following medicines, as their use with GLICONORM requires caution:

• glucocorticoids (e.g. as cream, tablets, or by injection) (medicines used to treat inflammation)
• sympathomimetics (medicines acting on the nervous system, stimulating the heart and increasing blood pressure)
• medicines that increase urine production (diuretics)
• medicines such as ranolazine (used to treat angina pectoris, a condition characterized by chest pain or discomfort, often triggered by physical exertion or excessive activity) or cimetidine (used to treat ulcers). Your doctor may ask you to monitor your blood sugar levels frequently and may adjust the dose of GLICONORM or other diabetes medicines accordingly.
• medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• some medicines for treating high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)

GLICONORM with food and alcohol
Take this medicine with meals and do not take it if you eat very little or are fasting.
Avoid excessive alcohol consumption during treatment with GLICONORM, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”), enhance its hypoglycaemic effect (lowering blood sugar levels), and cause palpitations, headache, and vomiting (antabuse-like reactions) (see section 2. “Do not take GLICONORM”), especially if you have liver disease (hepatic insufficiency).

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take GLICONORM if you are pregnant or breastfeeding (see section 2. “Do not take GLICONORM”).

Driving and using machines
Do not drive or operate machinery if you experience reduced reflex responsiveness or have difficulty concentrating. This may be due to an episode of low blood sugar (hypoglycaemia).

3. How to take GLICONORM

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Each treatment course (initial treatment or switch from another medicine) must be prescribed by your doctor.
Your doctor will determine the most appropriate dose for you based on your condition.
Always strictly follow your doctor's recommendations regarding dosage, method of
administration, diet, and physical activity.
The recommended dose in adults is 1–3 tablets per day, divided among the main meals.
If you have reduced kidney function, your doctor may prescribe a lower dose.
The break line on the tablet is intended to facilitate breaking the tablet to make swallowing easier, and not for dividing it into equal doses.

If you take more GLICONORM than you should
If you have taken/ingested an excessive dose of GLICONORM, contact your doctor immediately or go to the nearest hospital.
In case of overdose, you may experience:

• hypoglycaemia, which may lead to behavioural disturbances or loss of consciousness (coma). In such cases, take carbohydrates orally (sugars) or go to hospital, where, if necessary, sugars will be administered intravenously or appropriate treatment given.
• lactic acidosis (difficulty breathing, stomach pain, lowered body temperature, and loss of consciousness – see section 2. “Warnings and precautions”). In this case, go to hospital immediately where you will receive appropriate treatment (e.g. haemodialysis, a blood filtration system).

If you forget to take GLICONORM
Do not take a double dose to make up for the forgotten tablet.

If you stop taking GLICONORM
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
GLICONORM may cause a very rare (may occur in up to 1 in 10,000 people) but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking GLICONORM and must immediately contact your doctor or go to the nearest hospital, because lactic acidosis can lead to coma.
The possible side effects are listed below according to the following frequency:
Very common (may affect more than 1 in 10 people)

• nausea
• loss of appetite (anorexia)
• vomiting
• diarrhoea
• abdominal pain
  To prevent these side effects, take GLICONORM in 1–3 divided daily doses with or after meals.

Common (may affect up to 1 in 10 people)

• headache
• taste disturbances

Very rare (may affect up to 1 in 10,000 people)

• skin redness (erythema)
• itching (pruritus)
• skin redness accompanied by itching (urticaria)
• severe skin reaction (erythema multiforme)
• inflammation of blood vessels due to allergy (allergic vasculitis)
• low blood sugar levels (hypoglycaemia) (see section “Warnings and precautions”)
• lactic acidosis (build-up of lactic acid in the body) (see section “Warnings and precautions”)
• low or reduced levels of vitamin B__ in the blood (symptoms may include extreme tiredness (fatigue), red and sore tongue (glossitis), tingling sensations (paraesthesiae), or pale or yellowish skin). Your doctor may prescribe certain tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health conditions. Reduced absorption and reduced levels of vitamin B__ in the blood may occur during long-term use of GLICONORM. Inform your doctor if you have a blood disorder (megaloblastic anaemia). (See section “Warnings and precautions”)
• reduced number of white blood cells in the blood (leucopenia)
• reduced number of platelets in the blood (thrombocytopenia)
• reduced number of granulocytes in the blood, a type of white blood cell (agranulocytosis)
• disease caused by the destruction of certain blood cells, the red blood cells (haemolytic anaemia)
• reduced function of the bone marrow, the tissue that produces blood cells (aplastic anaemia)
• reduced number of all types of blood cells (pancytopenia)
• abnormalities in liver function tests
• impairment of bile flow (a substance important for digestion) (cholestasis)
• inflammation of the liver (hepatitis)
• allergic reactions

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store GLICONORM

This medicine does not require any special storage conditions.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "EXP". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What GLICONORM contains

• The active substances are glibenclamide 5 mg and metformin hydrochloride 500 mg.
• The other components are: maize starch, anhydrous colloidal silica, microcrystalline cellulose, gelatin, glycerol 85 percent, talc, magnesium stearate, hypromellose, titanium dioxide, macrogol 400.

Description of the appearance of GLICONORM and package contents
GLICONORM is available as film-coated tablets, which are divisible.
It is supplied in a carton containing 36 film-coated tablets.
Marketing Authorization Holder and Manufacturer
ABIOGEN PHARMA S.p.A.
Via Meucci, 36 – Ospedaletto - Pisa