DIAGLIMET 5 mg/500 mg Film-Coated Tablets

Зміст інструкції

1. DIAGLIMET 5mg + 500mg film-coated tablets
   1. What is DIAGLIMET and what is it used for
   2. What you need to know before taking DIAGLIMET
   3. How to take DIAGLIMET
   4. Possible Undesirable Effects
   5. How to store DIAGLIMET
   6. Contents of the pack and other information

DIAGLIMET 5mg + 500mg film-coated tablets

GLIBENCLAMIDE + METFORMIN HYDROCHLORIDE

Read this leaflet carefully before taking this medicine as 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 pass it on to others, even if they have the same symptoms as you, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What DIAGLIMET is and what it is used for
• 2. What you need to know before you take 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 is DIAGLIMET and what is it used for

DIAGLIMET is an antidiabetic medicine (lowers blood glucose levels) for oral use,
which contains two active ingredients:

• metformin hydrochloride (belonging to the biguanide class)
• glibenclamide (belonging to the sulfonylurea class).

DIAGLIMET is indicated in adultsin the treatment of non-insulin-
dependent diabetes mellitus (also called type 2), non-ketoacidotic (i.e. that does not involve an increase
in the levels of substances called “ketone bodies” in the urine or blood) when glucose levels are not controllable with diet alone or combined treatment with diet and
sulfonylureas (medicines used to treat diabetes).

2. What you need to 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 suffer from “latent” diabetes (which has not yet manifested) or suspect you have diabetes;
• if you suffer from a form of diabetes that occurs during pregnancy (gestational);
• if you suffer from a form of diabetes for which insulin administration is necessary (insulin-dependent);
• if you suffer from diabetes that is not controlled, associated, for example, with severe hyperglycemia (high blood glucose levels), nausea, vomiting, diarrhea, 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 can lead to diabetic precoma. Symptoms include stomach pain, rapid and deep breathing, drowsiness and breath with an unusually fruity odor;
• if you suffer from loss of consciousness or a feeling of loss of consciousness due to diabetes (coma or diabetic precoma);
• if you suffer from 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 may alter your kidney function;
• if you are going to undergo an examination to evaluate kidney function (intravenous urography);
• if you suffer from diseases that can alter the way your kidneys work (e.g. if you have lost a lot of fluids, if you have a serious infection in progress or suffer from a decreased blood flow to all organs);
• if you suffer from severe heart or blood vessel problems (heart failure, recent heart attack, cardiogenic or infectious shock, peripheral arterial circulation disorders);
• if you suffer from severe respiratory problems (respiratory failure);
• if you suffer from a disease of the adrenal glands (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 (severely hypocaloric diets) or especially if you are fasting (see section “DIAGLIMET with food and alcohol”);
• if you suffer from severe nerve and muscle diseases (dystrophic);
• if you suffer from acute severe bleeding;
• if you suffer from decreased blood flow to all organs (shock);
• if you suffer from localized destructive processes in some tissues, which undergo death (gangrene);
• if you have undergone or will undergo surgery, do not take DIAGLIMET for the two days before or after the surgery;
• if you are pregnant;
• if you are breastfeeding;
• if you are to undergo examinations that involve the 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 expose you to a greater risk of life-threatening heart and blood vessel diseases (cardiovascular mortality), especially if you also suffer from heart artery disorders (coronary heart disease), compared to treatment with other medicines for diabetes such as metformin or gliclazide.
Patients aged 65 years or older are particularly sensitive to the hypoglycemic action of glibenclamide and are therefore at greater risk of hypoglycemia. In the elderly, low blood sugar levels can be somewhat difficult to recognize. The initial dose of glibenclamide and the maintenance dose must be carefully established by the attending physician to avoid hypoglycemic reactions.

Risk of lactic acidosis
DIAGLIMET can cause a very rare but very serious side effect called lactic acidosis, especially if the kidneys do not work properly. The risk of developing lactic acidosis is greater in the presence of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see below for more information), liver problems and any other medical condition characterized by reduced oxygen supply to a part of the body (such as in the case of severe heart disease).
If you have any of the medical conditions described above, consult your doctor for further instructions.

Stop taking DIAGLIMET for a short period of time if you have a medical condition that may be associated with dehydration(significant loss of body fluids) such as severe vomiting, diarrhea, fever, exposure to heat or if you drink less fluids than usual. Consult your doctor for further instructions.

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

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• a generalized feeling of unwellness associated with severe fatigue
• difficulty breathing
• reduced body temperature and slower heart rate

Lactic acidosis is a medical emergency and must be treated in hospital.

Contact your doctor immediately for further instructions if:

• you know you have an inherited genetic disease that affects the mitochondria (the components that produce energy inside cells), 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 these symptoms after starting metformin: seizures, decreased cognitive abilities, difficulty with body movements, symptoms indicating nerve damage (e.g. pain or numbness), migraine and hearing loss.

During treatment with DIAGLIMET, the doctor will check the functioning of your kidneys 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 to lower blood pressure) or non-steroidal anti-inflammatory drugs (NSAIDs) (to treat inflammation) that may alter kidney function
• if you experience symptoms of hypoglycemia (low blood sugar) such as headache, irritability, difficulty concentrating, sleep disturbances, tremors, nausea, excessive sweating, feeling of hunger.

If you experience these symptoms, take carbohydrates (sugars) and IMMEDIATELY INFORM YOUR DOCTOR: you may need to undergo blood tests, suspend therapy or be hospitalized to bring blood sugar levels back under control.
Symptoms of hypoglycemia can occur, albeit rarely, especially:

• if you are debilitated
• if you are elderly
• if you perform unusual physical exertion
• if you have an irregular diet
• if you drink alcohol
• if you have kidney or liver problems

Also inform the doctor in case of trauma, surgery, infectious diseases and fever. The doctor may temporarily prescribe insulin therapy for better control of blood sugar levels.

Also inform the doctor:

• if you are to undergo major surgery. In this case, you will have to stop taking DIAGLIMET during the surgery and for a certain period of time thereafter. The doctor will decide when to stop and when to resume treatment with DIAGLIMET.
• if you suffer from a deficiency of an enzyme called glucose-6-phosphate dehydrogenase (G6PD). In this case, your doctor will administer this medicine with caution or advise you to take another medicine to avoid the risk of hemolytic anemia (red blood cell disease, a type of blood cell);
• if you suffer from a blood disease called megaloblastic anemia, caused by reduced absorption of vitamin B (see section 4. “Possible side effects”).

Continue the diet prescribed by your doctor and undergo 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 to be injected with an iodine-containing contrast agent into the bloodstream, for example to take an X-ray, you must stop taking DIAGLIMET before or during the injection. The doctor will decide when to stop and when to resume treatment with DIAGLIMET.
Tell your doctor if you are taking, have recently taken or may take any other medicine. You may need to have your blood sugar and kidney function checked more often, or your doctor may decide to adjust the dosage of DIAGLIMET.
It is particularly important to mention the following:

• the following drugs that can increase the action of DIAGLIMET:
• dicoumarol and derivatives (medicines to make the blood more fluid)
• monoamine oxidase inhibitors (medicines to treat depression)
• antibiotics (medicines to treat infections, such as sulfonamides, quinolones (mainly fluoroquinolones such as gatifloxacin, ciprofloxacin, etc.) and chloramphenicol)
• phenylbutazone and derivatives (medicines to treat inflammation and pain)
• cyclophosphamide (medicine to treat tumors)
• probenecid (medicine to treat gout, a disease that causes inflammation and pain in the joints)
• fibrates (medicines to lower cholesterol)
• pheniramidol (medicine to treat pain)
• salicylates (medicines to treat inflammation)
• oral miconazole (medicine used to treat fungal infections)
• sulfinpyrazone (medicine to prevent heart attacks)
• perexiline (medicine to treat heart disease)
• medicines containing alcohol (see section “DIAGLIMET with food and alcohol”)
• the following drugs that can decrease the action 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 (medicines with a tranquilizing action)
• phenytoin and barbiturates (medicines used to treat epilepsy)
• H-antagonist drugs (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, tell 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 that act 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 that manifests with pain or discomfort in the chest) or cimetidine (medicine used to treat ulcers). The doctor may

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

• medicines used for the treatment of pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• some medicines for the treatment of 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 increase the hypoglycemic action (which lowers blood sugar levels), and cause a feeling of perceiving your heartbeat (palpitations), headache and vomiting (disulfiram-like reactions) (see section 2. “Do not take DIAGLIMET”), especially if you suffer from a liver disease (hepatic insufficiency).

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.

Do nottake DIAGLIMET if you are pregnant or breastfeeding (see section 2. “Do not take DIAGLIMET”).

Driving and operating machinery
Donot drive and do not operate machinery if you experience a reduction in alertness or if you have
difficulty concentrating. This may be a consequence of an episode of low blood sugar levels
(hypoglycemia).

3. How to take DIAGLIMET

Take this medicine following exactly the instructions of your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Each treatment (first treatment or switch from other medicines) must be prescribed by your
doctor. Your doctor will establish the best dose for you based on your condition.
Always carefully respect the doctor's recommendations regarding the dosage, the method of
administration, diet and physical activity.
The recommended dose in adults is 1-3 tablets per day, divided at main meals.
The score line on the tablet is to facilitate breaking it in order to swallow the tablet more
easily and not to divide it into equal doses.
If you have reduced kidney function, your doctor may prescribe a lower dose.

If you take more DIAGLIMET than you should
In case of ingestion/taking of an excessive dose of DIAGLIMET, immediately inform your
doctor or go to the nearest hospital.
In case of excessive dosage, you may experience:

• hypoglycemia, which can lead to behavioral disturbances or loss of consciousness (coma). In this case, take carbohydrates orally (sugars) or go to the hospital where, if necessary, they will administer sugars through a vein or suitable therapy.
• stomach disorders
• lactic acidosis(difficulty breathing, abdominal pain, lowering of body temperature andloss of consciousness -see paragraph 2. “Warnings and precautions”). In this case, go to the hospital where you will undergo appropriate treatments (e.g. hemodialysis, 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 doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible Undesirable Effects

Like all medicines, this medicine can cause undesirable effects, although not everyone will experience them.
DIAGLIMET may cause a very rare (may affect up to 1 in

• 10,000) but very serious undesirable effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking DIAGLIMET and immediately contact yourdoctor or the nearest hospital,because lactic acidosis can lead to coma.

If you experience symptoms of lactic acidosis(loss of appetite, nausea, fever,
vomiting, muscle cramps, increased breathing rate and depth, malaise, abdominal pain,
diarrhea, possible numbness or loss of consciousness) during treatment, STOPtreatment
and go to the nearest hospital.
Possible undesirable 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
• diarrhea
• abdominal pain To prevent these undesirable effects, take DIAGLIMET in 1-3 daily doses during or after meals.

common (may affect up to 1 in 10 people)

• headache
• taste alteration

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

• skin redness (erythema)
• itching
• skin rashes accompanied by itching (urticaria)
• severe skin reaction (erythema multiforme)
• inflammation of blood vessels due to an allergy (allergic vasculitis)
• low blood sugar levels (hypoglycemia) (see section “Warnings and precautions”)
• lactic acidosis (build-up of lactic acid in the body) (see section “Warnings and precautions”) reduced or low levels of vitamin B in the blood (symptoms may include extreme fatigue, sore and red tongue (glossitis), tingling (paresthesia) or pale or yellowish skin). Your doctor may prescribe some tests to find the cause of the symptoms because some of these may also be caused by diabetes or other health problems not related to it, decreased absorption and levels of vitamin B in the blood during long-term use of GLICONORM. Tell your doctor if you suffer from a blood disease (megaloblastic anemia). (see section “Warnings and precautions”)
• reduced number of white blood cells (leukopenia)
• reduced number of platelets in the blood (thrombocytopenia)
• reduced number of granulocytes in the blood, a type of white blood cells (agranulocytosis)
• disease due to the destruction of some blood cells, red blood cells (hemolytic anemia)
• reduced bone marrow function, the tissue that produces blood cells (bone marrow aplasia)
• reduced number of all types of cells present in the blood (pancytopenia)
• alterations in liver function tests
• impaired bile flow (substance useful for digestion) (cholestasis)
• liver inflammation (hepatitis)
• allergic reactions

Reporting of undesirable effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through 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 pack after SCAD. The expiry
date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What DIAGLIMET contains

• The active ingredients are glibenclamide 5 mg and metformin hydrochloride 500 mg.
• The other ingredients are: corn 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 contents of the pack
DIAGLIMET is presented as film-coated tablets.
It is available in a pack of 36 tablets.

Marketing authorisation holder and manufacturer
ABIOGEN PHARMA S.p.A.
Via Meucci, 36 – Ospedaletto – Pisa