Diaglimet

Italy
Brand name Diaglimet
Form tablets, film-coated
Active substance / Dosage
GLIBENCLAMIDE
METFORMIN HYDROCHLORIDE
Prescription type Prescription only
ATC code
A10BD02
Registration number 034693
Manufacturer ABIOGEN PHARMA S.P.A.

Table of Contents

Package leaflet: Information for the patient

DIAGLIMET 5mg + 500mg film-coated tablets

GLIBENCLAMIDE + METFORMIN HYDROCHLORIDE
Please read this leaflet carefully before you take 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 other people, even if their symptoms are the same as yours, because it could be harmful.
  • If you experience any side effect, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

What is in this leaflet:

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

1. What DIAGLIMET is and what it is used for

DIAGLIMET is an oral antihyperglycaemic medicine (lowers blood glucose levels)
containing two active substances:

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

DIAGLIMET is indicated in adults for the treatment of non-insulin-dependent
diabetes mellitus (also called 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 combined treatment with diet and sulphonylureas (medicines used to treat diabetes).

2. What you should know before taking DIAGLIMET

Do not take DIAGLIMET

  • 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 (such as glibenclamide and sulfonamides);
  • if you have latent diabetes (not yet manifested) or suspect you have diabetes;
  • if you have gestational diabetes (diabetes occurring during pregnancy);
  • if you have a form of diabetes requiring insulin treatment (insulin-dependent);
  • 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 have loss of consciousness or feeling of loss of 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 alter 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);
  • if you have severe heart or blood vessel problems (heart failure, cardiac insufficiency, recent heart attack, cardiogenic or toxi-infectious shock, peripheral arterial circulation disorders);
  • 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 “DIAGLIMET with food and alcohol”);
  • if you eat very little (very low-calorie diets) or especially if you are fasting (see section “DIAGLIMET with food and alcohol”);
  • if you have severe nerve and muscle 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 DIAGLIMET 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 DIAGLIMET”).

Warnings and precautions
Talk to your doctor or pharmacist before taking DIAGLIMET.
Taking DIAGLIMET may increase your risk of fatal heart and blood vessel diseases (cardiovascular mortality), especially if you also have heart artery disorders (coronary heart disease), compared to treatment with other diabetes medicines such as metformin or gliclazide.
Patients aged 65 years or older are particularly sensitive to the hypoglycaemic action 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
DIAGLIMET may cause a very rare but very serious adverse effect called lactic acidosis, particularly if your 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.
Temporarily stop taking DIAGLIMET if you develop a medical condition that may be associated with dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, exposure to heat, or if you are drinking less fluid than usual. Consult your doctor for further instructions.
If you experience any of the symptoms of lactic acidosis, stop taking DIAGLIMET 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, Maternal Inherited Diabetes and Deafness);
  • you experience any of the following symptoms after starting metformin: seizures, reduced cognitive abilities, movement difficulties, symptoms indicating nerve damage (e.g. pain or numbness), headache, and deafness.

During treatment with DIAGLIMET, your doctor will check your kidney function at least once a year, or more frequently:

  • if you are elderly and/or if kidney function worsens
  • if you are taking diuretic or antihypertensive medicines (to increase urine production or lower blood pressure) or non-steroidal anti-inflammatory drugs (NSAIDs) (to treat inflammation) that could alter your kidney function
  • if you experience symptoms of hypoglycaemia (low blood sugar levels) such as headache, irritability, difficulty concentrating, sleep disturbances, tremors, nausea, excessive sweating, feeling of hunger.

If you experience these symptoms, take carbohydrates (sugars) and INFORM YOUR DOCTOR IMMEDIATELY: you may need blood tests, temporary discontinuation of treatment, or hospitalization to bring your blood glucose back under control.
Hypoglycaemia symptoms may occur, although rarely, especially:

  • if you are debilitated
  • 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 may temporarily prescribe insulin therapy for better control of blood sugar levels.
Also inform your doctor:

  • if you are scheduled for major surgery. In this case, you will need to stop taking DIAGLIMET during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to resume treatment with DIAGLIMET.
  • 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 have regular blood tests even during treatment with DIAGLIMET.
Children and adolescents
Do not give DIAGLIMET to children or adolescents, as it is not indicated for them.
Other medicines and DIAGLIMET
If you are scheduled to receive an injection of an iodinated contrast agent into the bloodstream, for example for an X-ray, you must stop taking DIAGLIMET before or during the injection. Your doctor will decide when to stop and when to resume treatment with DIAGLIMET.
Inform your doctor if you are taking, have recently taken, or might take any other medicine. You may need to monitor your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of DIAGLIMET.
It is particularly important to mention the following:

  • the following medicines that may increase the effect of DIAGLIMET:
    • dicoumarol and derivatives (medicines to make blood more fluid)
    • monoamine oxidase inhibitors (medicines for treating depression)
    • antibiotics (medicines for treating infections, such as sulfonamides, quinolones (mainly fluoroquinolones such as gatifloxacin, ciprofloxacin, etc.) and chloramphenicol)
    • phenylbutazone and derivatives (medicines for treating inflammation and pain)
    • cyclophosphamide (medicine for treating cancer)
    • 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 for preventing heart attacks)
    • perhexiline (medicine for treating heart disease)
    • medicines containing alcohol (see section “DIAGLIMET with food and alcohol”)
  • the following medicines that may decrease the effect of DIAGLIMET:
    • 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)
    • H-antagonists (medicines used in the treatment of ulcers, stomach perforations)
    • ß-blockers (medicines used for treating 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. Additionally, inform your doctor if you are taking the following medicines, as their use with DIAGLIMET requires caution:
  • glucocorticoids (e.g. in 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 (medicine used to treat angina pectoris, a disorder characterized by chest pain or discomfort, often triggered by physical exertion or excessive activity) or cimetidine (medicine used to treat ulcers). Your doctor may

ask you to monitor your blood sugar levels frequently and adjust
the dosage of DIAGLIMET or other diabetes medicines you are
taking 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)

DIAGLIMET with food and alcohol
Take this medicine with meals and do not take it if you eat very little or if you are fasting.
Avoid excessive alcohol consumption during treatment with DIAGLIMET, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”), may enhance the hypoglycaemic effect (lowering blood sugar levels), and may cause awareness of your heartbeat (palpitations), headache, and vomiting (antabuse-like reactions) (see section 2. “Do not take DIAGLIMET”), especially if you have liver disease (hepatic insufficiency).
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Do not take DIAGLIMET if you are pregnant or breastfeeding (see section 2. “Do not take DIAGLIMET”).
Driving and using machines
Do not drive or operate machinery if you experience reduced reflexes or have difficulty concentrating. This may be due to an episode of low blood sugar (hypoglycaemia).

3. How to take DIAGLIMET

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Every treatment (initial treatment or switch from other medicines) must be prescribed
by your doctor. Your doctor will determine the most appropriate dose for you based on your condition.
Always carefully follow your doctor's recommendations regarding dosage, method of administration, diet, and physical activity.
The recommended dose in adults is 1–3 tablets daily, divided with main meals.
The score line on the tablet is intended to facilitate swallowing by making it easier to break the tablet and does not serve to divide it into equal doses.
If you have reduced kidney function, your doctor may prescribe you a lower dose.
If you take more DIAGLIMET than you should
If you ingest/absorb an excessive dose of DIAGLIMET, 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 this case, take carbohydrates orally (sugars) or go to hospital, where, if necessary, sugars or appropriate treatment will be administered intravenously.
  • stomach disturbances
  • lactic acidosis (difficulty breathing, abdominal pain, decreased body temperature, and loss of consciousness – see section 2. “Warnings and precautions”). In this case, go to hospital immediately for appropriate treatment (e.g. haemodialysis, a blood filtration system).

If you forget to take DIAGLIMET
Do not take a double dose to make up for the missed tablet.
If you stop taking DIAGLIMET
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
DIAGLIMET 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 DIAGLIMET and must immediately contact your doctor or go to the nearest hospital, because lactic acidosis can lead to coma.
If you experience symptoms of lactic acidosis during treatment (loss of appetite, nausea, fever, vomiting, muscle cramps, increased depth and rate of breathing, malaise, abdominal pain, diarrhoea, or possible numbness or loss of consciousness), STOP treatment immediately and go to the nearest hospital.

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 DIAGLIMET in 1–3 divided daily doses during or after meals.

Common (may affect up to 1 in 10 people)

  • headache
  • altered taste

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 (accumulation of lactic acid in the body) (see section “Warnings and precautions”)
    low or reduced levels of vitamin B({12}) in the blood (symptoms may include extreme tiredness (fatigue), red and sore tongue (glossitis), tingling sensations (paraesthesias), or pale or yellowish skin). Your doctor may carry out certain tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health problems. Reduced absorption and reduced levels of vitamin B({12}) in the blood may occur during long-term use of GLICONORM. Inform your doctor if you suffer from 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 destruction of certain blood cells, the red blood cells (haemolytic anaemia)
  • reduced function of the bone marrow, the tissue that produces blood cells (bone marrow aplasia)
  • reduced number of all types of blood cells (pancytopenia)
  • abnormalities in liver function tests
  • impairment of bile flow (a substance useful for digestion) (cholestasis)
  • inflammation of the liver (hepatitis)
  • allergic reactions

Reporting of side effects
If you experience any side effect, 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 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 DIAGLIMET

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 which is stated on the carton 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 no longer required. This will help protect the environment.

6. Package contents and other information

What DIAGLIMET 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 DIAGLIMET and package contents
DIAGLIMET is available as film-coated tablets.
It is supplied in a carton containing 36 tablets.
Marketing Authorization Holder and Manufacturer
ABIOGEN PHARMA S.p.A.
Via Meucci, 36 – Ospedaletto – Pisa