Diamicron - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Gliclazide

Diamicron 30 mg modified release tablets

Diamicron package inserts are available for pack sizes:
  • Diamicron 30 mg modified release tablets
  • Diamicron 60 mg modified release tablets

Indications Why is Diamicron used? What is it for?

Diamicron 30 mg is a blood sugar lowering drug (oral antidiabetic medicine belonging to the sulfonylurea group).

Diamicron 30 mg is indicated in adults for the treatment of certain types of diabetes (type 2 diabetes mellitus) when diet, exercise and weight loss alone are not sufficient to maintain a correct blood sugar level. .

Contraindications When Diamicron should not be used

Do not take Diamicron 30 mg

  • if you are allergic to gliclazide or to any of the other ingredients of Diamicron 30 mg (listed in section 6) or to other medicines of the same group (sulfonylureas), or to other related medicines (hypoglycemic sulphonamides);
  • if you have insulin-dependent (type I) diabetes;
  • if you have ketone bodies and sugar in your urine (this means you may have diabetic keto-acidosis), if you are in a pre-coma or diabetic coma;
  • if you have severe kidney or liver disease;
  • if you are taking medicines to treat fungal infections (miconazole, see section "Taking Diamicron 30 mg with other medicines");
  • if you are breast-feeding (see section 'Pregnancy and breast-feeding').

Precautions for use What you need to know before taking Diamicron

Follow your doctor's directions for achieving appropriate blood sugar levels. In addition to taking the tablet regularly, observe a dietary regimen, exercise and reduce weight if necessary.

During treatment with gliclazide, regular monitoring of the level of sugar in the blood (and possibly in the urine) and also of glycosylated hemoglobin (HbA1c) is necessary. In the first few weeks of treatment, the risk of excessive decrease in blood sugar may increase. (hypoglycemia) This is why close medical supervision is necessary.

Your blood sugar level can drop too low (hypoglycemia):

  • if you eat meals irregularly or skip them completely,
  • if you are fasting,
  • if you are malnourished,
  • if you change your eating habits,
  • if your physical activity increases and your carbohydrate intake is not adequate for this increase,
  • if you take alcohol, especially on an empty stomach,
  • if you take other medicines or natural remedies at the same time,
  • if you take too high doses of gliclazide,
  • if you suffer from particular hormonal disorders (dysfunction of the thyroid gland, pituitary gland or adrenal cortex),
  • if your kidney or liver function is severely reduced.

In case of low blood sugar you may experience the following symptoms: headache, intense hunger, nausea, vomiting, weakness, sleep disturbance, agitation, aggression, difficulty concentrating, reduced attention and reaction time, depression, confusion, speech or vision disturbances, tremor, sensory disturbances, dizziness and a sense of helplessness.

The following signs and symptoms may also occur: sweating, clammy skin, anxiety, rapid or irregular heartbeat, high blood pressure, sudden sharp chest pain radiating to surrounding areas (angina pectoris).

If your blood sugar continues to drop, you may experience severe confusion (delirium), seizures, loss of self-control, shortness of breath, slow heart rate and loss of consciousness.

In most cases the symptoms of low blood sugar go away very quickly by taking sugar in various forms such as glucose tablets, sugar cubes, sugary juices or tea. You should therefore always carry sugar with you (glucose tablets, sugar cubes). Remember that artificial sweeteners are not effective. Contact your doctor or the nearest hospital if sugar intake does not help or if your symptoms return.

Symptoms of low blood sugar may not show, be less noticeable, come on slowly, or you may not notice in time that your blood sugar has dropped. This can happen if you are an elderly patient taking certain medicines (e.g. those that affect the central nervous system and beta-blockers). If you are in stressful situations (e.g. accidents, surgery, fever, etc.) your doctor may temporarily switch to insulin therapy.

Symptoms of high blood sugar (hyperglycaemia) may appear when gliclazide has not yet reduced your blood sugar sufficiently, when you have not followed the treatment prescribed by your doctor or in situations of particular stress. These can include thirst, the need to urinate frequently, dry mouth, dry itchy skin, skin infections and decreased efficiency.

If such symptoms occur, you should contact your doctor or pharmacist.

If you have a family history or hereditary condition of glucose-6-phosphate dehydrogenase (G6PD) deficiency (red blood cell disorder), you may experience a drop in hemoglobin levels and a breakdown of red blood cells (haemolytic anemia). Contact your doctor before taking this medicine.

The use of Diamicron 30 mg is not recommended in children due to the lack of data in this regard.

Interactions Which drugs or foods can modify the effect of Diamicron

Other medicines and Diamicron 30 mg

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, even those obtained without a prescription, as these may interact with Diamicron 30 mg. The blood sugar lowering effect of gliclazide may be increased and signs of low blood sugar may appear when taking any of the following medicines:

  • other medicines used to treat high blood sugar levels (oral antidiabetics, GLP-1 receptor agonists or insulin),
  • antibiotics (e.g. sulfonamides, clarithromycin),
  • medicines to treat high blood pressure or heart failure (beta blockers, ACE inhibitors such as captopril or enalapril),
  • medicines used to treat fungal infections (miconazole, fluconazole),
  • medicines to treat stomach or duodenal ulcers (H2 receptor antagonists),
  • medicines to treat depression (monoamine oxidase inhibitors),
  • pain relievers or antirheumatics (phenylbutazone, ibuprofen),
  • medicines containing alcohol.

The blood glucose lowering effects of gliclazide may be weakened and an increase in blood sugar may occur when one of the following medicines is taken:

  • medicines to treat central nervous system disorders (chlorpromazine),
  • medicines to reduce inflammation (corticosteroids),
  • medicines to treat asthma or used during labor (intravenous salbutamol, ritodrine and terbutaline),
  • medicines to treat breast disorders, heavy menstrual bleeding, endometriosis (danazol),

Diamicron 30 mg may increase the effects of medicines that reduce blood clotting (eg warfarin).

Consult your doctor before taking any other medicines. If you are hospitalized please tell the medical staff that you are taking Diamicron 30 mg.

Taking Diamicron 30 mg with food, drink and alcohol

Diamicron 30 mg can be taken with food and non-alcoholic drinks.

Drinking alcohol is not recommended as it can alter diabetes control in unpredictable ways.

Warnings It is important to know that:

Pregnancy and breastfeeding

Diamicron 30 mg is not recommended during pregnancy. If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breast-feeding, ask your doctor or pharmacist for advice before taking this medicine.

You should not take Diamicron 30 mg while breastfeeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Your ability to concentrate or react may be impaired if your blood sugar is too low (hypoglycaemia), too high (hyperglycaemia) or if you develop vision problems as a result of these conditions. Bear in mind that it can harm yourself or others (e.g. when driving cars or using machines). Ask your doctor for advice if you can drive a car if you have:

  • frequent episodes of low blood sugar levels (hypoglycaemia),
  • little or no obvious signs of low blood sugar (hypoglycaemia).

Dose, Method and Time of Administration How to use Diamicron: Posology

Dosage

Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, you should consult your doctor or pharmacist.

The dose is determined by your doctor based on your blood sugar levels and possibly your urine. Changes in external factors (e.g. weight reduction, lifestyle changes, stress) or improvements in blood sugar control may require changes in gliclazide doses.

The recommended dose is 1 to 4 tablets (maximum 120 mg) in a single administration at the time of breakfast. This depends on the response to treatment.

In case of combination therapy of Diamicron 30 mg with metformin, an alpha-glycosidase inhibitor, a thiazolidinedione, a dipethidylpeptidase-4 inhibitor, a GLP-1 receptor agonist or insulin, your doctor will determine the appropriate dose of each for you. medicinal.

Talk to your doctor or pharmacist if you have the impression that your blood sugar levels are high despite taking this medicine.

Method and route of administration

Oral use.

Swallow the tablets whole without chewing them. Take the tablet (s) with a glass of water at breakfast time (and preferably at the same time each day). You should always have a meal after taking the tablet (s).

Overdose What to do if you have taken too much Diamicron

If you take more Diamicron 30 mg than you should

If you take too many tablets contact your doctor or the nearest hospital emergency department immediately. The signs of overdose are those of a low blood sugar level (hypoglycaemia) described in section 2. These symptoms can be improved by taking sugar immediately (4 to 6 lumps) or sugary drinks followed by a large snack or meal . If the patient is unconscious, contact the doctor immediately and call the emergency services.

The same must be done if someone, for example a child, has taken the product accidentally. Food or drink should not be given to unconscious patients. Make sure there is always an informed person who can call a doctor in an emergency.

If you forget to take Diamicron 30 mg

It is important to take the medicine every day because regular treatment is more effective. However, if you miss a dose of Diamicron 30 mg, take your next dose regularly at the same time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Diamicron 30 mg

As diabetes treatment usually lasts a lifetime, you should consult your doctor before stopping treatment with this medicine. Stopping it can cause blood sugar levels to rise (hyperglycemia), which increases the risk of developing diabetes complications.

If you have any further questions on the use of Diamicron 30 mg, ask your doctor or pharmacist.

Side Effects What are the side effects of Diamicron

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The most commonly observed side effect is a low blood sugar level (hypoglycaemia). For symptoms and signs see the section "Warnings and precautions". If left untreated, these symptoms can progress to sleepiness, loss of consciousness and possibly coma If a low blood sugar episode is severe or prolonged, even if temporarily controlled with sugar intake, contact your doctor immediately.

Liver disorders

There have been isolated cases of liver function abnormalities, which can cause yellowing of the skin and eyes. If they appear, contact your doctor immediately. Symptoms usually go away if the medicine is stopped. The doctor will decide whether to discontinue treatment.

Skin disorders

Skin reactions such as rash, redness, itching and hives, angioedema (rapid swelling of tissues such as the eyelids, face, lips, mouth, throat or tongue which may cause difficulty in breathing) have been reported. The rashes can progress to a spread of the blisters all over the body or to peeling of the skin.

Blood disorders

Symptoms such as paleness, prolonged bleeding, bruising, throat inflammation and fever have been reported following a decrease in the number of blood cells (eg platelets, red and white blood cells). These symptoms usually disappear when treatment is stopped.

Disorders of digestion

Abdominal pain, nausea, vomiting, indigestion, diarrhea and constipation. These effects are reduced when Diamicron 30 mg is taken with a meal, as recommended.

Visual disturbances

Vision may be disturbed for a short time especially at the start of treatment. This effect is due to changes in the blood sugar level.

As with other sulfonylureas, the following adverse events have been observed: severe changes in the number of blood cells and allergic inflammation of the blood vessel walls, decreased levels of sodium in the blood (hyponatremia), symptoms of liver failure (e.g. jaundice) which in most cases have disappeared following discontinuation of the sulfonylureas, but which in isolated cases can lead to life-threatening liver failure.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.

Expiry and Retention

Keep this medicine out of the reach and sight of children.

Do not use this medicine after the expiry date which is stated on the carton and blister. The expiry date refers to the last day of the month.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.

Composition and pharmaceutical form

What Diamicron 30 mg contains

The active ingredient is gliclazide. Each tablet contains 30 mg of gliclazide in the modified release formulation.

The other ingredients are: dibasic calcium phosphate dihydrate, maltodextrin, hypromellose, magnesium stearate, anhydrous colloidal silica.

What Diamicron 30 mg looks like and contents of the pack

Diamicron 30 mg modified-release tablets are white, oblong, debossed on both sides; "DIA 30" on one side and on the other. The tablets are available in blister packs contained in cartons of 7, 10, 14, 20, 28, 30, 56, 60, 84, 90, 100, 112, 120, 180 or 500 tablets.

Not all pack sizes may be marketed.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Diamicron is available in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER O 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, COMPLETE DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, ADDITIONAL DETAILED INSTRUCTIONS AND QUALITY CONTROLS

01.0 NAME OF THE MEDICINAL PRODUCT

DIAMICRON 30 MG

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

One tablet contains gliclazide 30 mg

For the full list of excipients see section 6.1

03.0 PHARMACEUTICAL FORM

Modified-release tablet

White oblong tablet debossed on both sides, with "DIA 30" on one side and on the other.

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Non-insulin-dependent (type 2) diabetes in adults, when dietary measures, exercise and weight loss alone are not sufficient to control blood sugar.

04.2 Posology and method of administration

The daily dosage can vary from 1 to 4 tablets, or from 30 to 120 mg, in a single daily administration at breakfast.

It is recommended that the tablets be swallowed whole.

If you miss a dose, do not increase the dose the next day.

As with all hypoglycemic agents, the dosage should be adapted according to the individual metabolic response of each patient (glycaemia, HbA1c).

Initial dose:

The recommended starting dose is 30 mg per day.

If glycemic control is satisfactory, this posology can be used as a maintenance treatment.

If glycemic control is not satisfactory, the dosage can be gradually increased to 60, 90 or 120 mg per day. The interval between each dose increase should be at least one month, except in patients in whom there is no reduction in blood glucose after 2 weeks of treatment. In these cases it is possible to increase the dosage at the end of the second week of treatment.

The maximum recommended dose is 120 mg per day.

Replacement of Diamicron 80 mg tablets with Diamicron 30 mg modified release tablets:

1 Diamicron 80 mg tablet is equivalent to 1 Diamicron 30 mg tablet. Substitution can then be made by carefully monitoring blood glucose.

Replacement of another oral antidiabetic with Diamicron 30 mg:

Diamicron 30 mg can be used to replace other oral antidiabetics.

To switch to Diamicron 30 mg it is necessary to take into account the posology and the half-life of the antidiabetic that is being replaced.

In general, the transition will take place without a transition phase. It should start with a dose of 30 mg which will subsequently be adjusted, as described above, according to the glycemic response of each individual patient.

In the event that a hypoglycemic sulfonylurea with a prolonged half-life is replaced, it may be necessary to respect a therapeutic window of a few days, in order to avoid an additive effect of the two products, which could cause hypoglycaemia.

During the replacement phase, it is recommended to follow the same procedure indicated for the initiation of a therapy with Diamicron 30 mg, starting the treatment at the dosage of 30 mg per day and gradually increasing it according to the metabolic response.

Combination with other antidiabetics:

Diamicron 30 mg can be administered in combination with biguanides, alpha glucosidase inhibitors or insulin.

In patients insufficiently controlled with Diamicron 30 mg, insulin therapy can be initiated simultaneously under close medical supervision.

Special populations

Elderly patients

Diamicron 30 mg should be prescribed following the same dosing schedule recommended for patients below 65 years of age.

Patients with renal insufficiency

In patients with mild to moderate renal insufficiency, the same dosage schedule can be followed as in those with normal renal function, keeping the patient closely monitored. These findings are confirmed by clinical studies.

Patients at risk of hypoglycemic crisis for:

- states of malnutrition or malnutrition

- severe or poorly compensated endocrine pathologies (hypopituitarism, hypothyroidism, adrenocorticotropic insufficiency),

- discontinuation of prolonged and / or high dose cortisone therapy,

- severe vascular disease (severe coronary artery disease, severe carotid compromise, diffuse vascular disease);

it is recommended to start treatment at the minimum dose of 30 mg per day.

Pediatric population

The efficacy and safety of Diamicron 30 mg in children and adolescents has not been established. No clinical data are available in children.

04.3 Contraindications

- Known hypersensitivity to gliclazide or to any of the excipients listed in section 6.1, to other sulfonylureas or to sulfonamides;

- type I diabetes;

- pre-coma and diabetic coma; diabetic ketoacidosis;

- severe hepatic or renal insufficiency: in these cases it is recommended to use insulin;

- ongoing treatment with miconazole (see section 4.5);

- breastfeeding (see section 4.6).

04.4 Special warnings and appropriate precautions for use

Hypoglycemia:

This treatment should only be prescribed to patients who eat meals regularly (including breakfast). A regular intake of carbohydrates is important due to the increased risk of hypoglycaemia following a delay in eating a meal or due to an insufficient or low carbohydrate diet. The onset of hypoglycaemia is more likely in low-calorie conditions, following intense or prolonged exertion, after ingestion of alcohol or during treatment with a combination of hypoglycemic agents.

Hypoglycaemia may occur during treatment with sulfonylureas (see section 4.8). In some cases it can be severe and prolonged. It may be necessary to hospitalize the patient and administer glucose for a few days.

A careful selection of patients, of the posology used and precise instructions to the patient are necessary to reduce the risk of hypoglycaemic crises.

Factors that increase the risk of hypoglycemia:

- refusal or (especially in the elderly patient) inability of the patient to cooperate;

- malnutrition, irregular mealtimes or missed meals, periods of fasting or changes in the diet;

- imbalance between physical exercise and the introduction of carbohydrates;

- kidney failure;

- severe hepatic insufficiency;

- overdose of Diamicron;

- some endocrine dysfunctions: thyroid insufficiency, pituitary and adrenal insufficiency;

- concomitant administration of some other drugs (see section 4.5).

Renal and hepatic insufficiency: The pharmacokinetics and / or pharmacodynamics of gliclazide may be modified in patients with severe hepatic or renal insufficiency. Since hypoglycaemia may be prolonged in these patients, they should be adequately controlled.

Patient information:

The risks of a hypo, its symptoms (see section 4.8) and its treatment, as well as the predisposing factors for its development, must be explained to the patient and his family.

The patient should be informed of the importance of adhering to the diet, following a regular exercise program and regularly checking blood glucose.

Insufficient blood glucose control: The glycemic balance of a patient treated with an antidiabetic may be affected by the occurrence of: fever, trauma, infection or surgery. In some cases, insulin may be required.

The hypoglycemic efficacy of all oral antidiabetic agents, including gliclazide, tends to lessen over time in many patients. This may be due to an aggravation of diabetes or a decrease in response to treatment.

This phenomenon is called secondary failure, to distinguish it from primary failure, in which an active ingredient is ineffective as a primary intention treatment. Before classifying a patient's treatment as secondary failure, dose adjustment and adherence to diet should be evaluated.

Laboratory analysis: to check blood glucose it is recommended to perform the determination of the level of glycated hemoglobin (or fasting blood glucose in the venous blood). Self-monitoring of blood glucose may also be helpful.

Treatment of patients with G6PD deficiency with sulfonylureas can lead to haemolytic anemia. As gliclazide belongs to the class of sulfonylureas it should be used with caution in such patients and an alternative therapy to sulfonylureas should be considered.

04.5 Interactions with other medicinal products and other forms of interaction

1) The following substances may increase the risk of hypoglycemia

Contraindicated associations

- Miconazole (systemic route, oral gel): increased hypoglycemic action, with possible onset of hypoglycaemic symptoms, up to coma.

Associations not recommended

- Phenylbutazone (systemic route): increase in the hypoglycemic action of sulfonylureas (displacement of their bonds with plasma proteins and / or decrease in their elimination). Preferably use another anti-inflammatory; otherwise warn the patient and emphasize the importance of self-control Where necessary, adjust the dosage during and after treatment with the anti-inflammatory.

- Alcohol: increased hypoglycaemic reaction (by inhibition of compensatory reactions), which can lead to the onset of hypoglycemic coma.

Avoid drinking alcoholic beverages and alcohol-containing medicines.

Associations requiring precautions for use

An enhancement of the hypoglycemic effect and therefore, in some cases, a hypoglycemic crisis, could occur following the concomitant administration of one of the following drugs:

other antidiabetics (insulin, acarbose, metformin, thiazolidinediones, dipeptidylpeptidase-4 inhibitors, GLP-1 receptor agonists) beta-blockers, fluconazole, angiotensin converting enzyme inhibitors (captopril, enalapril), H2 receptor antagonists, MAOIs, sulfonamides, clarithromycin and non-steroidal anti-inflammatory drugs.

2) The following substances they can promote an increase in blood sugar

Associations not recommended

- Danazol: diabetogenic effect of danazol

If the use of this active ingredient cannot be avoided, warn the patient and emphasize the importance of blood and urine glucose control. An adjustment of the antidiabetic dosage may be necessary during and after treatment with danazol.

Associations requiring precautions for use

- Chlorpromazine (neuroleptic): at high doses (higher than 100 mg / day) increase in blood sugar (reduced release of insulin).

Advise the patient and emphasize the importance of glycemic control. Adjustment of the antidiabetic dosage may be necessary during and after treatment with the neuroleptic.

- Glucocorticoids (systemic and local route: intra-articular, cutaneous and rectal preparations) and tetracosactide: increase in blood sugar with possible ketosis (decrease in carbohydrate tolerance due to glucocorticoids).

Inform the patient and emphasize the importance of blood glucose control, especially at the start of treatment. During and after treatment with glucocorticoids, it may be necessary to adjust the dosage of the antidiabetic.

- Ritodrine, salbutamol, terbutaline: (via E.V.)

Increased blood sugar by beta-2 stimulants.

Emphasize the importance of glycemic control. Switch to insulin if necessary.

3) Associations that must be taken into consideration

- Anticoagulant therapy (Warfarin)

Sulfonylureas can enhance the anticoagulant effect during associated therapy.

An adaptation of the dosage of the anticoagulant may be necessary.

04.6 Pregnancy and lactation

Pregnancy

There is no experience with the use of gliclazide in pregnant women, although there are some data available with other sulfonylureas.

In studies in laboratory animals, gliclazide was not teratogenic.

Control of diabetes must be achieved before conception to reduce the risk of birth defects related to decompensated diabetes.

In pregnancy, oral hypoglycemic agents are not indicated; Insulin is the drug of choice in the treatment of diabetes during pregnancy. It is recommended to switch from oral hypoglycemic treatment to insulin before planning a pregnancy or when pregnancy is established.

Feeding time

It is unknown whether gliclazide or its metabolites are excreted in human milk.

Given the risk of neonatal hypoglycemia, the drug is contraindicated in breastfeeding women.

04.7 Effects on ability to drive and use machines

Diamicron 30 mg has no known influence on the ability to drive and use machines. However, patients should be made aware of the symptoms of hypoglycaemia and should exercise caution when driving or using machines, especially at the start of treatment.

04.8 Undesirable effects

The following undesirable effects have been reported during the use of gliclazide.

Hypoglycemia

As with other sulfonylureas, treatment with Diamicron can cause hypoglycaemia, in case of irregular mealtimes and especially in case of missed meals.

Possible symptoms of hypoglycemia are: headache, acute sense of hunger, nausea, vomiting, asthenia, sleep disturbances, agitation, aggression, poor concentration, decreased alertness and reactivity, depression, confusion, visual and speech disturbances, aphasia, tremor, paresis, sensory disturbances, dizziness, feeling of helplessness, loss of self-control, delirium, convulsions, shallow breathing, bradycardia, drowsiness and loss of consciousness which can lead to coma and death.

In addition, signs of adrenergic counter-regulation may be observed: sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia.

Symptoms generally disappear after the introduction of carbohydrates (sugar). Conversely, artificial sweeteners have no effect. Experience with other sulfonylureas shows that, despite initially effective measures, hypoglycaemia can recur.

In case of severe or prolonged hypoglycemia, even if temporarily controlled by sugar intake, "immediate medical treatment or even" hospitalization is required.

Other side effects:

Gastrointestinal disorders such as abdominal pain, nausea, vomiting, dyspepsia, diarrhea, constipation have been reported: if they occur, they can be avoided or minimized if gliclazide is taken with breakfast.

The following side effects have been reported more rarely:

• skin and subcutaneous tissue disorders: rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis).

• haematological and lymphatic system disorders: haematological changes are rare. They may include anemia, leukopenia, thrombocytopenia, granulocytopenia, usually reversible on discontinuation of treatment.

• hepato-biliary disorders: elevation of liver enzymes (AST, ALT, alkaline phosphatase), hepatitis (isolated cases). Discontinue treatment if cholestatic jaundice occurs.

In general, the above symptoms subside with the interruption of treatment.

• visual disturbances: transient visual disturbances, linked to a change in blood glucose levels, may occur especially at the beginning of treatment.

• effects attributable to the therapeutic class:

As with other sulfonylureas, the following adverse events have been observed: cases of erythrocytopenia, agranulocytosis, haemolytic anemia, pancytopenia, allergic vasculitis, hyponatraemia, cases of elevated liver enzymes as well as liver failure (eg with cholestasis and jaundice) and hepatitis, which regressed after discontinuation of the sulfonylurea or resulted in life-threatening liver failure for the patient in isolated cases.

04.9 Overdose

Sulfonylurea overdose can cause hypoglycemia.

Modest symptoms of hypoglycemia, without loss of consciousness or other neurological signs, should be corrected with a carbohydrate intake, dosage adjustment and / or dietary modification. The patient has to be kept under strict control until the doctor is certain that the patient is out of danger.

Severe hypoglycaemic reactions, with coma, convulsions or other neurological disorders are possible and represent a "medical emergency that requires the immediate hospitalization of the patient."

If hypoglycaemic coma is diagnosed or suspected, 50 ml of concentrated glucose solution (20 to 30%) should be administered as i.v. quick. This should be followed by continuous perfusion of a more diluted (10%) glucose solution at a rate that keeps blood glucose above 1g / l. Patients should be kept under close surveillance and, based on their condition at the time, the doctor will decide if further checks are needed.

Due to the strong binding of gliclazide to plasma proteins, dialysis is not helpful to the patient.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Medicinal product category: sulfonamides, urea derivatives.

ATC code: A10BB09.

Gliclazide is a hypoglycemic sulfonylurea - oral antidiabetic agent that differs from related compounds by a heterocyclic ring containing an endocyclically bonded nitrogen atom.

Gliclazide lowers blood sugar by stimulating the secretion of insulin by the beta cells of the islets of Langerhans. The increased postprandial response to insulin and C-peptide secretion persists after 2 years of treatment.

In addition to these metabolic properties, gliclazide possesses haemovascular properties.

Effects on insulin release

In the type 2 diabetic patient, gliclazide restores the early peak of insulin secretion in response to glucose and increases the second phase of insulin secretion. A significant increase in insulin response is observed in response to a meal or a glucose stimulus.

Hemovascular properties

Gliclazide slows down the microthrombosis process thanks to two mechanisms that may be involved in the onset of diabetes complications:

- partial inhibition of platelet aggregation and adhesiveness with a decrease in platelet activation markers (beta thromboglobulin, Thromboxane B2);

- action on the fibrinolytic activity of the vascular endothelium with an increase in tPA activity.

05.2 Pharmacokinetic properties

Absorption

Plasma concentrations progressively increase in the first 6 hours after dosing, then remain in the plateau phase between the sixth and twelfth hour after administration.

The intra-individual variations are of limited magnitude.

The absorption of gliclazide is complete. Food intake does not change its absorption rate, nor its bioavailability.

Distribution

Plasma protein binding is approximately 95%.The volume of distribution is approximately 30 liters.

The once daily administration of 30 mg Diamicron allows to maintain an effective plasma concentration of gliclazide over 24 hours.

Biotransformation

Gliclazide is mainly metabolised by the liver and excreted in the urine: less than 1% is recovered unchanged in the urine. No active metabolites have been detected in plasma.

Elimination

The elimination half-life of gliclazide varies between 12 and 20 hours.

Linearity / non-linearity

In the therapeutic range up to 120 mg the relationship between the administered dose and the area under the concentration versus time curve is linear.

Special populations

Senior citizens

No clinically significant changes in pharmacokinetic parameters were observed in elderly subjects.

05.3 Preclinical safety data

On the basis of conventional studies of repeated dose toxicity and genotoxicity, preclinical data reveal no special hazard for humans.

Long-term carcinogenicity studies have not been conducted.

Studies conducted on laboratory animals did not reveal any teratogenic effects; however, a decrease in weight was observed in fetuses of mothers receiving doses 25 times higher than that recommended in humans.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

Calcium dibasic phosphate dihydrate,

maltodextrin,

hypromellose,

magnesium stearate,

anhydrous colloidal silica.

06.2 Incompatibility

Not relevant.

06.3 Period of validity

3 years.

06.4 Special precautions for storage

This medicine does not require any special storage conditions.

06.5 Nature of the immediate packaging and contents of the package

7,10,14,20,28,30,56,60,84,90,100,112,120, 180 and 500 tablets in Aluminum / Poly (vinyl chloride) blisters in cardboard boxes.

Not all pack sizes may be marketed.

06.6 Instructions for use and handling

No special instructions.

07.0 MARKETING AUTHORIZATION HOLDER

LES LABORATOIRES SERVIER

50, rue Carnot

92284 Suresnes cedex- FRANCE

08.0 MARKETING AUTHORIZATION NUMBER

023404027 / M: 7 modified-release tablets

023404039 / M: 10 modified release tablets

023404041 / M: 14 modified-release tablets

023404054 / M: 20 modified release tablets

023404066 / M: 28 modified-release tablets

023404078 / M: 30 modified release tablets

023404080 / M: 56 modified-release tablets

023404092 / M: 60 modified-release tablets

023404167 / M: 84 modified-release tablets

023404104 / M: 90 modified release tablets

023404116 / M: 100 modified release tablets

023404128 / M: 112 modified release tablets

023404130 / M: 120 modified release tablets

023404142 / M: 180 modified-release tablets

023404155 / M: 500 modified-release tablets

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

Date of first authorization: 19/02/2003

Renewal of the authorization: 10/2011

10.0 DATE OF REVISION OF THE TEXT

10/2012

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

none:  tumors video-exercises food-related diseases