Package Insert: Information for the Patient

Gliclazide Combix 60 mg Modified Release EFG Tablets

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.

If you have any questions, consult your doctor or pharmacist.

• This medication has been prescribed to you alone, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

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Gliclazida Combix is a medication that reduces blood sugar levels (oral antidiabetic medication belonging to the sulfonilureas group).

Gliclazida Combix is used in a certain type of diabetes in adults (type 2 diabetes mellitus), when diet, physical exercise, and weight loss alone are not sufficient to ensure normal blood sugar levels.

Do not take Gliclazida Combix

• if you are allergic to gliclazide or any of the other ingredients of this medicine (listed in section 6), or to other medicines in the same group (sulfonilureas), or to other related medicines (sulfamidas hypoglycemic);
• if you have insulin-dependent diabetes (type 1);
• if you have ketones and sugar in your urine (which may mean you have diabetic ketoacidosis), a precoma or diabetic coma;
• if you have severe renal or hepatic impairment;
• if you are receiving medicines for the treatment of fungal infections (miconazole), see section “Use of other medicines”;
• if you are breastfeeding (see section “Pregnancy and lactation”).

Warnings and precautions

Consult your doctor before starting to take Gliclazida Combix.

You should follow the treatment prescribed by your doctor to achieve adequate blood sugar levels.

This means that, in addition to regular intake of the tablets, you should control your diet, exercise physically, and, if necessary, lose weight.

During treatment with gliclazide, regular monitoring of your blood sugar level (and possibly in urine) and also of your hemoglobin A1c (HbA1c) is necessary.

In the first weeks of treatment, the risk of having low blood sugar levels (hypoglycemia) may be increased. Close clinical supervision is especially necessary.

Low blood sugar levels (hypoglycemia) may appear:

-if you do not maintain regularity in meals or skip them,

-if you are fasting,

-if you are malnourished,

-if you change your diet,

-if you increase your physical activity without an adequate increase in carbohydrate intake,

-if you drink alcohol, especially if you skip meals,

-if you take other medicines or natural remedies at the same time,

-if you take too high doses of gliclazide,

-if you suffer from certain hormonal disorders (functional alterations of the thyroid gland, pituitary gland, or adrenal cortex),

-if your renal or hepatic function is severely impaired,

If you experience low blood sugar levels, you may experience the following symptoms: headache, intense hunger, nausea, vomiting, fatigue, sleep disturbances, agitation, aggression, lack of concentration, decreased alertness and reaction time, depression, confusion, visual and speech disturbances, tremors, sensory disturbances, dizziness, and vulnerability.

The following signs and symptoms may also be observed: sweating, moist skin, anxiety, rapid heart rate or irregular heart rhythm, high blood pressure, severe chest pain that may extend to adjacent areas (angina pectoris).

If blood sugar levels continue to drop, you may experience a great confusion (delirium), seizures, loss of self-control, your breathing may become shallow, and your heart rate may slow down, leading to unconsciousness.

In most cases, the symptoms of low blood sugar levels disappear quickly after consuming sugar, for example, glucose tablets, sugar lumps, sweet juice, or sweet tea.

Therefore, you should always carry something sweet with you (glucose tablets, sugar lumps). Remember that artificial sweeteners are not effective. If sugar intake does not help or symptoms reappear, please contact your doctor or the nearest hospital.

The symptoms of low blood sugar levels may not appear, be mild, or develop slowly, or you may not realize in time that your blood sugar level has dropped. This can happen in elderly patients taking certain medications (e.g., those acting on the central nervous system and beta-blockers).

If you are under stress (accidents, surgical interventions, fever, etc.), your doctor may temporarily change your treatment to insulin.

The symptoms of high blood sugar levels (hyperglycemia) may appear when gliclazide has not yet reduced blood sugar levels sufficiently, when you have not followed the treatment prescribed by your doctor, or in special situations of stress. They may include thirst, dry mouth, dry skin with itching, skin infections, decreased performance, and frequent urination.

If these symptoms appear, you should contact your doctor or pharmacist.

Alterations in blood glucose levels (low blood sugar and high blood sugar) may occur when gliclazide is prescribed at the same time as other medications belonging to a class of antibiotics called fluoroquinolones, especially in elderly patients. In this case, your doctor will remind you of the importance of controlling your blood glucose levels.

If you have a family history or know that you have a hereditary deficiency of glucose-6-phosphate dehydrogenase (G6PD) (alteration in red blood cells), a decrease in hemoglobin levels and destruction of red blood cells (hemolytic anemia) may occur. Consult your doctor before taking this medicine.

Children and adolescents

Gliclazida Combix is not recommended for use in children due to the absence of data.

Other medicines and Gliclazida Combix

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

The hypoglycemic effect of gliclazide may be potentiated and signs of low blood sugar levels may appear when taking one of the following medications:

• other medicines used to treat high blood sugar levels (oral antidiabetics, GLP-1 receptor agonists, or insulin),
• antibiotics (e.g., sulfamides, clarithromycin),
• medicines for treating high blood pressure or heart failure (beta-blockers, IECAs such as captopril, or enalapril),
• medicines for treating fungal infections (miconazole, fluconazole),
• medicines for treating stomach or duodenal ulcers (H2 receptor antagonists),
• medicines for treating depression (monoamine oxidase inhibitors),
• analgesics or anti-inflammatory drugs (phenylbutazone, ibuprofen),
• medicines containing alcohol,
• preparations containing St. John's Wort (Hypericum perforatum).

The hypoglycemic effect of gliclazide may be reduced and blood sugar levels may increase if taking one of the following medications:

• medicines for treating central nervous system disorders (chlorpromazine),
• anti-inflammatory drugs (corticosteroids),
• medicines for treating asthma or used during delivery (salbutamol intravenously, ritodrine, and terbutaline),
• medicines for treating breast disorders, heavy menstrual bleeding, and endometriosis (danazol).

When a medication belonging to the class of antibiotics called fluoroquinolones is taken at the same time as Gliclazida Combix, alterations in blood glucose levels (low blood sugar and high blood sugar) may occur, especially in elderly patients.

Gliclazida Combix may increase the effect of medications that reduce blood coagulation (warfarin).

Consult your doctor before using any other medicine. If you enter a hospital, inform the staff that you are taking Gliclazida Combix.

Taking Gliclazida Combix with food, drinks, and alcohol

Gliclazida Combix can be taken with meals and non-alcoholic drinks.

The consumption of alcohol is not recommended, as it may unpredictably alter your diabetes control.

Pregnancy and lactation

The use of Gliclazida Combix is not recommended during pregnancy.

If you are pregnant, think you may be pregnant, or intend to become pregnant, consult your doctor before taking this medicine.

You should not use Gliclazida Combix if you are breastfeeding.

Driving and operating machines

Your ability to concentrate and react may be affected due to symptoms caused by hypoglycemia or hyperglycemia, such as visual disturbances. This may be hazardous in situations where these skills are important (e.g., driving or operating machines). Therefore, consult your doctor if it is recommended to drive or operate machines.

Consult your doctor if you can drive in the following cases:

• if you have frequent episodes of low blood sugar levels (hypoglycemia),
• if you have mild or no signs that warn you of low blood sugar levels (hypoglycemia).

Gliclazida Combix contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medicine.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The dose will be determined by your doctor, depending on your blood sugar levels and possibly in urine.

Adjustments in gliclazide doses may be necessary due to changes in external factors (weight loss, lifestyle change, stress) or improvements in blood sugar control. The recommended daily dose is 30 to 120 mg (maximum 120 mg) in a single dose with breakfast. This depends on the response to treatment.

Gliclazida Combix is for oral use. Take the tablet(s) with a glass of water at breakfast (preferably at the same time every day). Swallow your tablets whole. Do not chew or crush. Always eat after taking the tablet(s).

If you start a combined therapy of Gliclazida Combix with metformin, an alpha-glucosidase inhibitor, a thiazolidinedione, a dipeptidyl peptidase-4 inhibitor, a GLP-1 receptor agonist, or insulin, your doctor will individually determine the appropriate dose of each medication for you.

Contact your doctor or pharmacist if you notice that your blood sugar levels are high despite taking this medication as prescribed by your doctor.

If you take more Gliclazida Combix than you should

If you take too many tablets, contact your doctor immediately, the nearest hospital emergency department, or call the Toxicology Information Service (phone 91 562 04 20) indicating the medication and the amount ingested.

The symptoms of overdose are those of low blood sugar (hypoglycemia) described in section 2. Symptoms may improve by taking immediately sugar (4 to 6 sugar cubes) or sweet drinks, followed by a substantial snack or meal. If the patient is unconscious, inform your doctor immediately and call emergency services. The same should be done if someone, for example a child, has taken the medication by accident. Do not feed or give drinks to unconscious people.

Make sure that there is always someone informed who can call your doctor in case of an emergency.

If you forgot to take Gliclazida Combix

It is essential to take your medication every day since regular treatment is more effective.

However, if you forget to take a dose of Gliclazida Combix, take the next dose at the usual time.

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Gliclazida Combix

Since diabetes treatment is usually lifelong, you should consult your doctor before stopping this medication. Stopping treatment could cause high blood sugar (hyperglycemia) that increases the risk of developing diabetes complications.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The most frequently observed side effect is low blood sugar (hypoglycemia). For symptoms and signs, see the section “Warnings and precautions”.

If these symptoms are not treated, they could progress to drowsiness, loss of consciousness, or possibly coma. You should seek immediate medical attention if the episode of low blood sugar is severe or prolonged, even if it is temporarily controlled with sugar intake.

Liver disorders

Isolated cases of abnormal liver function have been reported, which can cause yellowing of the skin and eyes. If you experience this, seek immediate medical attention. These symptoms usually disappear when treatment is discontinued. Your doctor will decide if it is necessary to discontinue treatment.

Skin disorders

Reports of skin reactions such as skin rash, erythema, itching, hives, angioedema (rapid swelling of tissues such as eyelids, face, lips, mouth, tongue, or throat that can cause difficulty breathing) have been reported. The skin rash can evolve to the formation of widespread blisters or skin peeling.

Exceptionally, reports of severe hypersensitivity reactions (DRESS) have been reported:

initially as symptoms similar to the flu and a skin rash on the face, followed by a generalized skin rash with high fever.

Blood disorders

Reports of decreases in the number of blood cells (e.g., platelets, red and white blood cells) have been reported, which can cause pallor, prolonged bleeding, hematomas, sore throat, and fever. These symptoms usually disappear when treatment is discontinued.

Gastrointestinal disorders

Abdominal pain, nausea, vomiting, indigestion, diarrhea, and constipation. These effects are reduced when Gliclazida Combix is taken with meals, as recommended.

Eye disorders

Your vision may be temporarily affected, especially at the start of treatment. This effect is due to changes in blood sugar levels.

Like other sulfonylureas, the following adverse reactions have been observed: severe changes in the number of blood cells and allergic inflammation of blood vessel walls, decreased sodium in the blood (hyponatremia), symptoms of liver insufficiency (e.g., jaundice) that in most cases disappeared after withdrawal of the sulfonylurea, but in isolated cases may lead to liver insufficiency with vital threat.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the blister pack after CAD. The expiration date is the last day of the month indicated.

This medication does not require special conditions for conservation.

Medications should not be disposed of through drains or in the trash. Dispose of the containers and themedications that you no longer need at the SIGRE collection pointof the pharmacy. If in doubt, ask yourpharmacist how to dispose of the containers and the medications that you no longer need. By doing so, you will help protect the environment.

Composition of Gliclazida Combix 60 mg

-The active ingredient is gliclazida. Each modified-release tablet contains 60 mg of gliclazida.

-The other components are: lactose monohydrate, anhydrous sodium carbonate, hypromellose, anhydrous colloidal silica, and magnesium stearate.

Appearance of the product and contents of the packaging

Gliclazida Combix is a white or cream-colored, uncoated, oblong, modified-release tablet, engraved with ‘60’ on one face and smooth on the other. The tablets are available in blisters in packs of 60 and 100 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Responsible for Manufacturing

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

or

Netpharmalab Consulting Services

Crta. De Fuencarral, 22

28108 Alcobendas (Madrid)

Spain

Last review date of this leaflet: February 2018

The detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/