Consumer medicine information

Glyade

Gliclazide

BRAND INFORMATION

Brand name

Glyade

Active ingredient

Gliclazide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Glyade.

What is in this leaflet

This leaflet answers some common questions about GLYADE.

It does not contain all the available information

Reading this leaflet does not take the place of talking to your doctor, pharmacist, or diabetes educator.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking GLYADE against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor, pharmacist, or diabetes educator.

Keep this leaflet with the medicine.

You may need to read it again.

What GLYADE is

The name of your medicine is GLYADE.

GLYADE contains the active ingredient 'gliclazide'.

Gliclazide belongs to a group of medicines called sulphonylureas.

What GLYADE is used for

GLYADE is used to control blood glucose (sugar) in patients with Type II diabetes mellitus. This type of diabetes is also known as non-insulin-dependent diabetes (NIDDM), or maturity-onset diabetes).

Why GLYADE is used for Type II diabetes mellitus

GLYADE is used when diet and exercise are not enough to control your blood glucose.

GLYADE can be used alone or together with insulin or other medicines for treating diabetes.

How it works

Glucose is used by the body as fuel, and all people have glucose circulating in their blood. In diabetes, levels of blood glucose are higher than is needed, which is also known as hyperglycaemia.

If your blood glucose is not properly controlled, you may experience hypoglycaemia (low blood glucose) or hyperglycaemia (high blood glucose). High blood glucose can lead to serious problems with our heart, circulation and/or kidneys.

It is very important to control high blood glucose whether or not you feel unwell. This really helps to avoid serious long-term health problems, which can involve the heart, eyes, circulation, and/or kidneys.

A section at the end of this leaflet contains advice about recognising and treating hyperglycaemia.

GLYADE is used when diet and exercise are not enough to control your blood glucose properly. It lowers blood glucose by increasing the amount of insulin (a hormone that controls blood glucose levels) produced by your pancreas.

As with many medicines used for the treatment of diabetes, there is a possibility that blood glucose levels may become very low during treatment with GLYADE. This is known as hypoglycaemia.

A section at the end of this leaflet contains advice about recognising and treating hypoglycaemia.

GLYADE is available only with a doctor's prescription.

GLYADE is not addictive

Ask your doctor if you have any questions about why GLYADE has been prescribed for you.

Before you take GLYADE

There are some people who should not take GLYADE. Please read the lists below.

If you think any of these situations apply to you, or you have any questions, please consult your doctor, pharmacist, or diabetes educator.

Do not take GLYADE if

  • you are allergic to: gliclazide, or any of the other ingredients listed at the end of this leaflet.
  • you have had an allergic reaction to any other sulphonylureas, or related medicines such as sulfa antibiotics or to thiazide diuretics (a type of "fluid" or "water" tablet).
    Symptoms of an allergic reaction to GLYADE or to these medicines may include skin rash, itchiness or hives, shortness of breath, swelling of the face, lips or tongue, muscle pain or tenderness or joint pain.
    If you are not sure if you have an allergy to GLYADE, check with your doctor.
  • are pregnant or trying to become pregnant.
    GLYADE may affect your developing baby if you take it during pregnancy. Insulin is more suitable for controlling blood glucose during pregnancy. Your doctor will usually replace GLYADE with insulin while you are pregnant.
  • are breastfeeding or plan to breast-feed.
    GLYADE is not recommended while you are breastfeeding. It is not known whether GLYADE passes into breast milk.
  • you have Type 1 diabetes mellitus (also known as insulin-dependent diabetes (IDDM), or juvenile-onset diabetes).
  • you have unstable diabetes
  • you have diabetic ketoacidosis (a problem which affects the acidity of your blood and can lead to coma - which is mainly associated with Type 1 diabetes).
  • you have severe kidney disease
  • you have severe liver disease
  • you are taking an antibiotic medicine containing the active ingredient miconazole
  • the expiry date (EXP) printed on the pack.
    If you take it after the expiry date has passed, it may not work as well.
  • the packaging is torn or shows signs of tampering.
    If it is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking GLYADE, talk to your doctor.

For children

Do not give GLYADE to a child. There is no experience with the use of GLYADE in children.

For older people

Elderly people can generally use GLYADE safely.

There are no special instructions for older people taking GLYADE.

Tell your doctor straight away if:

  • you are pregnant or plan to become pregnant or are breast-feeding.
    Your doctor can discuss with you the risks and benefits involved.
  • you are allergic to any of the ingredients listed at the end of this leaflet; to any other medicines; or to any other substances, such as foods, preservatives or dyes
  • you have an intolerance to some sugars as GLYADE contains lactose
  • If you have a family history of or know you have the hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency (abnormality of red blood cells), lowering of the haemoglobin level and breakdown of red blood cells (haemolytic anaemia) can occur.
  • you have had any of the following medical conditions:
    - kidney disease
    - liver disease
    - a history of diabetic coma.
    - adrenal, pituitary or thyroid problems
    - heart failure
  • you have any medical condition, or do anything, that may increase the risk of hyperglycaemia - for example:
    - you are ill or feeling unwell (especially with fever or infection)
    - you are injured
    - you are having surgery.
    - you are taking less GLYADE than prescribed
    - you are taking less exercise than normal
    - you are eating more carbohydrate than normal.
    - drinking alcoholic drinks.
    - not eating regular meals.
    - taking more exercise than usual.

If you have not told your doctor, pharmacist or diabetes educator about any of the above, tell them before you start taking GLYADE.

Taking other medicines

Tell your doctor, pharmacist or diabetes educator if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

Taking GLYADE may change the effect of some medicines, and some medicines may affect how well GLYADE works. You may need different amounts of your medication or to take different medicines.

Some medicines may lead to low blood glucose (hypoglycaemia) by increasing the blood-glucose-lowering effect of GLYADE.

These include:

  • some medicines used to treat fungal or yeast infections (miconazole which is contraindicated)
  • alcohol
  • other medicines used to treat diabetes (such as biguanides and insulin)
  • some medicines used to treat high blood pressure and other heart conditions (including angiotensin receptor blocker, beta-blockers)
  • some medicines used to treat depression and other mental illness (MAOIs)
  • some cholesterol-lowering
  • medicines (clofibrate)
  • some medicines used to treat arthritis, pain and inflammation (including high dose aspirin, ibuprofen, phenylbutazone)
  • some antibiotics (chloramphenicol; tetracyclines; long-acting sulphonamides)
  • some medicines used to treat acid reflux and stomach ulcers

Some medicines may lead to high blood glucose levels (hyperglycaemia) by weakening the blood glucose-lowering effect of GLYADE.

These include:

  • alcohol
  • some medicines for epilepsy (danazol)
  • some medicines used to treat depression and other mental illness (chlorpromazine)
  • some hormones used in hormone replacement therapy and oral contraceptives (oestrogen, progesterone)
  • St John's Wort (Hypericum perforatum) preparations used to treat depression
  • some medicines for asthma (salbutamol, intravenous terbutaline).
  • barbiturates, medicines used for sedation
  • glucocorticoids

Some medicines may lead to unstable blood glucose (low blood sugar and high blood sugar) when taken at the same time as GLYADE, especially in elderly patients.

These include:

  • A class of antibiotics called fluoroquinolones.

GLYADE may change the effects of some other medicines.

These include:

  • some medicines used to prevent blood clots (warfarin)

You may need different amounts of your medicine or you may need to take different medicines. Your doctor, pharmacist or diabetes educator can tell you what to do if you are taking any of these medicines. They also have a more complete list of medicines to be careful with or avoid while taking GLYADE.

Ask your doctor or pharmacist if you are not sure if you are taking any of these medicines.

How to take GLYADE

Follow all directions given to you by your doctor, pharmacist, and diabetes educator carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

Your doctor will tell you how many tablets to take each day. They may increase or decrease the dose, depending on your blood glucose levels.

When to take it

Swallow the tablets with a glass of water. GLYADE tablets can be broken in half. However they should not be crushed or chewed. Crushing or chewing the tablets may change the effectiveness of the tablet.

It is important to take your GLYADE at the same time each day - usually with breakfast. Taking GLYADE with food can help to minimise the risk of hypoglycaemia.

Do not skip meals while taking GLYADE.

How long to take it

Continue taking GLYADE for as long as your doctor recommends. Make sure you keep enough GLYADE to last over weekends and holidays.

GLYADE will help control your diabetes but will not cure it. Therefore, you may have to take it for a long time.

If you forget to take it

If is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as you remember (with food), then go back to taking your tablets as you would normally. Missed doses can cause high blood glucose (hyperglycaemia).

If you are not sure whether to skip the dose, talk to your doctor or pharmacist.

Do not take a double dose to make up for the dose you have missed. If you double a dose, this may cause low blood glucose (hypoglycaemia).

If you take too much (overdose)

Immediately telephone your doctor, Diabetes Australia or Poisons Information Centre (telephone in Australia: 13 11 26) for advice if you think that you or anyone else may have taken too much GLYADE. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much GLYADE together with other medicines for diabetes or alcohol, you may experience symptoms of low blood glucose (hypoglycaemia).

If not treated quickly, these symptoms may progress to loss of co-ordination, slurred speech, confusion, loss of consciousness and fitting.

At the first signs of hypoglycaemia, raise your blood glucose quickly by following the instructions at the end of this leaflet.

If you experience any of these symptoms, immediately get medical help.

While you are taking GLYADE

Things you must do

If you become pregnant while you are taking GLYADE, tell your doctor.

Tell all doctors, dentists, pharmacists and diabetes educators who are involved with your treatment that you are taking GLYADE.

If you are about to start taking any new medicines, tell you doctor and pharmacist that you are taking GLYADE.

Take GLYADE exactly as your doctor has prescribed. Otherwise you may not get the full benefits from treatment.

Make sure you check your blood glucose levels regularly. This is the best way to tell if your diabetes is being controlled properly. Your doctor or diabetes educator will show you how and when to do this.

Make sure that you, your friends, family and work colleagues can recognise the symptoms of hypoglycaemia and hyperglycaemia and know how to treat them. Instructions at the end of this leaflet can help you with this.

Visit your doctor regularly so that they can check on your progress.

Carefully follow your doctor's and dietician's advice on diet, drinking alcohol and exercise.

Tell your doctor immediately if you notice the return of any symptoms of hyperglycaemia that you had before starting GLYADE.

These may include lethargy or tiredness, headache, thirst, passing large amounts of urine and blurred vision.

These may be signs that GLYADE is no longer working, even though you may have been taking it successfully for some time.

Things you must not do

Do not give GLYADE to anyone else, even if they have the same condition as you.

Do not use GLYADE to treat other complaints unless your doctor tells you to.

Do not stop taking GLYADE, or change the dosage, without checking with your doctor.

Do not skip meals while taking GLYADE.

Things to be careful of

If you drink alcohol while taking GLYADE, you may get flushing, headache, breathing difficulties, rapid heart beat, stomach pains or feel sick and vomit.

Protect your skin when you are in the sun, especially between 10am and 3pm. Sulphonylureas (the group of medicines that GLYADE belongs to) may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight may cause a skin rash, itching, redness, or a severe sunburn.

If outdoors, wear protective clothing and use a 30+ sunscreen. If your skin does appear to be burning, tell your doctor immediately.

Be careful driving or operating machinery until you know how GLYADE affects you.

Also, be especially careful not to let your blood glucose levels fall too low. GLYADE may cause dizziness and drowsiness in some people. Low blood glucose levels may also slow your reaction time and affect your ability to drive or operate machinery. A section at the end of this leaflet contains advice about recognising and treating hypoglycaemia.

Drinking alcohol can make this worse. If either of these occurs, do not drive, operate machinery or do anything else that could be dangerous.

If you are travelling, it is a good idea to:

  • wear some form of identification showing you have diabetes
  • carry some form of sugar to treat hypoglycaemia if it occurs, for example, sugar sachets or jelly beans
  • carry emergency food rations in case of a delay, for example, dried fruit, biscuits or muesli bars
  • keep GLYADE readily available

If you become sick with a cold, fever or flu, it is very important to continue taking GLYADE, even if you fell unable to eat your normal meal. If you have trouble eating solid food, use sugar-sweetened drinks as a carbohydrate substitute or eat small amounts of bland food.

Your diabetes educator or dietician can give you a list of foods to use for sick days.

Side Effects

If you do not feel well while you are taking GLYADE then tell your doctor, pharmacist, or diabetes educator as soon as possible.

All medicines can have side effects. Most of the time they are not serious but sometimes they can be.

GLYADE helps most people with Type 2 diabetes, but it may sometimes have unwanted side effects. These can include:

  • hyPOglycaemia and hyPERglycaemia. A section at the end of this leaflet contains advice about recognising and treating hyPOglycaemia and hyPERglycaemia
  • runny or blocked nose, sneezing, facial pressure or pain, bronchitis, sore throat and discomfort when swallowing, upper respiratory infection, coughing,
  • back pain, arthralgia, arthrosis,
  • high blood pressure, chest pain,
  • Headache, unusual weakness,
  • Viral infection, urinary tract infection,
  • dizziness
  • stomach upset with symptoms like feeling sick, stomach pain, vomiting, diarrhoea or constipation.
  • decrease in the number of cells in the blood (e.g. platelets, red and white blood cells) which may cause paleness, prolonged bleeding, bruising, sore throat and fever have been reported. These symptoms usually vanish when the treatment is discontinued.
  • Increase of some hepatic enzymes levels, and exceptionally a liver disease,
  • your vision may be affected for a short time especially at the start of treatment. This effect is due to changes in blood sugar levels.

Other side effects are usually mild when they occur. Do not be alarmed by this list of possible side effects. You may not experience any of them.

However if you do - or if you notice anything else that is making you feel unwell - you should consult your doctor or pharmacist.

Other uncommon side effects have been reported and you may wish to discuss this issue with your doctor, pharmacist, or diabetes educator.

If any of the signs below occur stop taking GLYADE then tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital:

  • Skin rash, redness itching and/ or hives, blisters, angioedema (rapid swelling of tissues such as eyelids, face, lips, mouth, tongue or throat that may result in breathing difficulty) have been reported. Rash may progress to widespread blistering or peeling of the skin and may be the first sign of rare life threatening conditions (e.g. Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and severe hypersensitivity reactions (DRESS). Exceptionally, DRESS have been reported: initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature.

As for other sulphonylureas, the following adverse events have been observed: cases of severe changes in the number of blood cells and allergic inflammation of the wall of blood vessels, reduction in blood sodium (hyponatraemia), symptoms of liver impairment (e.g. jaundice) which in most cases disappeared after withdrawal of the sulfonylurea, but may lead to life-threatening liver failure in isolated cases.

After taking GLYADE

Storage

Keep your tablets in the pack until it is time to take them. GLYADE will not keep as well outside its blister packaging.

Keep them in a cool dry place where the temperature stays below 30°C.

Do not store medicines in the bathroom or near a sink. Do not leave them in a car or on a windowsill. Heat and dampness can destroy some medicines.

Keep GLYADE tablets where children cannot reach them. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking GLYADE, or the tablets have passed their expiry date, return any leftover tablets to your pharmacist for disposal.

Product description

What it looks like

GLYADE tablets are round, white and cross-scored on one side.

GLYADE tablets come in a blister strip. Each box contains 100 tablets.

Ingredients

Each tablet of GLYADE contains 80mg of gliclazide as the active ingredient and a number of inactive ingredients.

The inactive ingredients in GLYADE tablets include lactose monohydrate, maize starch, purified talc, magnesium stearate and pregelatinised maize starch.

The tablets are gluten free.

Manufacturer/Distributor

GLYADE is a product discovered and developed by Servier Research International.

It is distributed in Australia by:

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

GLYADE is registered on the Australian Register of Therapeutic Goods.

Australian Register Number: AUST R 70433

Recognising and treating hyPOglycaemia (very LOW blood sugar levels)

Hypoglycaemia may occur during GLYADE treatment.

The first signs of hypoglycaemia
are usually weakness, trembling or shaking, sweating, lightheadedness, dizziness, headache or lack of concentration, irritability, tearfulness, hunger, and/ or numbness around the lips and tongue.

At the first signs of hypoglycaemia take some sugar to raise your blood sugar level quickly. Do this by eating 5 to 7 jelly beans, 3 teaspoons of sugar or honey, drinking half a can of non-diet soft drink, taking 2-3 glucose tablets or a tube of glucose gel.

Then take some extra carbohydrates -
such as plain biscuits, fruit or milk - unless you are within 10-15 minutes of your next meal. Taking this extra carbohydrate will help to prevent a second drop in your blood glucose level.

If not treated quickly,
hypoglycaemia symptoms may progress to loss of co-ordination, slurred speech, confusion, fits or loss of consciousness.

If hypoglycaemia symptoms do not get better straight away after taking sugar then go to the Accident and Emergency department at your nearest hospital - if necessary by calling an ambulance.

Contact your doctor or diabetes educator for advice if you are concerned about hypoglycaemia.

Recognising and treating hyPERglycaemia (HIGH blood sugar levels)

Some people may feel fine when their glucose levels are high. Others notice symptoms of hyperglycaemia like tiredness, lack of energy, thirst, passing large amounts of urine, headache, and/or blurred vision.

If you notice symptoms of hyperglycaemia , or your blood sugar levels are high, tell your doctor immediately. You may need adjustments of the dose or type of medicines you are taking.

It is very important to control high blood glucose whether or not you feel unwell. This really helps to avoid serious long-term health problems, which can involve the heart, eyes, circulation, and/or kidneys.

If you experience any of the signs of hyperglycaemia (high blood glucose) contact your doctor or diabetes educator for advice immediately.

This leaflet was prepared in July 2019.

Published by MIMS October 2019

BRAND INFORMATION

Brand name

Glyade

Active ingredient

Gliclazide

Schedule

S4

 

Notes

Distributed by Alphapharm Pty Limited

1 Name of Medicine

Gliclazide.

6.7 Physicochemical Properties

Gliclazide has the chemical name 1-(3-azabicyclo[3.3.0]oct-3-yl)-3-p-tolylsulphonylurea. It is a white or almost white powder, practically insoluble in water, freely soluble in dichloromethane, sparingly soluble in acetone and slightly soluble in ethanol 96%. The melting point of gliclazide is approximately 168°C.
Molecular formula: C15H21N3O3S.

Chemical structure.


CAS number.

21187-98-4.

2 Qualitative and Quantitative Composition

Each Glyade tablet contains 80 mg of gliclazide.
Gliclazide is an oral hypoglycaemic sulphonylurea which differs from other related compounds by an N-containing heterocyclic ring with an endocyclic bond.
Excipient with known effect: each tablet contains 45 mg of lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Film-coated tablet: white, round, cross-scored on one side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacodynamics.

Gliclazide reduces blood glucose levels by stimulating insulin secretion from the β-cells of the islets of Langerhans. Gliclazide shows high affinity, strong selectivity and reversible binding to the β-cell KATP channels with a low affinity for cardiac and vascular KATP channels. Increased postprandial insulin and C-peptide secretion persists after two years of treatment.
In type II diabetes, gliclazide restores the first peak of insulin secretion in response to glucose and increases the second phase of insulin secretion. A significant increase in insulin release is seen in response to stimulation induced by a meal or glucose.
Gliclazide also has extra-pancreatic effects and haemovascular properties.
It has been shown to increase peripheral insulin sensitivity:
in muscle, euglycaemic hyperinsulinaemic clamp studies with gliclazide have demonstrated significantly increased (35%) insulin mediated glucose uptake which may improve diabetes control. Gliclazide potentiates insulin action on muscle glycogen synthase. These effects are consistent with a post-transcriptional action of gliclazide on GLUT4 glucose transporters;
studies on glucose turnover have further shown that gliclazide decreases hepatic glucose production, leading to an improvement in fasting blood glucose levels.
Gliclazide has been shown in some studies to have actions independent of that on glucose levels. These haemovascular effects of gliclazide include:
partial inhibition of platelet aggregation and adhesion with a decrease in markers of platelet activation (beta-thromboglobulin, thromboxane B2);
increased vascular endothelial fibrinolytic activity (increased tPA activity);
anti-oxidant properties, notably a reduction in plasma lipid peroxides and increased erythrocyte superoxide dismutase activity;
inhibition of the increased adhesiveness of type II diabetic patient's monocytes to endothelial cells in vitro.
The anti-oxidant, platelet inhibiting and fibrinolytic actions of gliclazide involve processes which have been implicated in the pathogenesis of vascular complications of type II diabetes. There is no clinical evidence that the haemovascular effects of gliclazide are of therapeutic benefit in type II diabetes patients.

5.2 Pharmacokinetic Properties

Absorption.

Gliclazide is absorbed in the gastrointestinal tract reaching peak serum concentrations within 4 to 6 hours. Single dose studies have demonstrated that maximal falls in blood glucose levels (23% of an 80 mg dose; 30% of a 160 mg dose) occur approximately five hours after drug administration; nine hours after a dose of 160 mg, a reduction of 20% was still in evidence. The half-life of gliclazide is approximately 12 hours.

Distribution.

Gliclazide is distributed to the extracellular fluid. In animals, high concentrations of the drug were found in the liver, kidneys, skin, lungs, skeletal muscle, intestinal and cardiac tissue. Penetration of gliclazide into the central nervous system was negligible. Gliclazide crosses the placental barrier and penetrates the foetus. The apparent volume of distribution of gliclazide (20 to 40% expressed as a percentage bodyweight) is low and probably reflects the high degree of protein binding (94.2% at a plasma concentration of approximately 8 microgram/mL).

Metabolism.

Little information is available in the metabolism of gliclazide. At least eight metabolites (three major) have been identified by thin layer and gas-liquid chromatography. Some of these are glucuronic acid conjugates; only one of the metabolites has been identified (p-toluene sulfonamide). The liver is the probable site of metabolism.

Excretion.

Approximately 70% of the administered dose appears to be excreted in the urine and 11% in the faeces. The urinary excretion of the drug is slow and the maximum rates do not occur until 7 to 10 hours after initial administration. The metabolic products are detectable in the urine 120 hours after oral administration. Faecal elimination is usually complete within 144 hours of oral administration.

Use in elderly.

No clinically significant modifications in the pharmacokinetic parameters have been observed in elderly patients.

5.3 Preclinical Safety Data

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Diabetes mellitus of the maturity onset type, which cannot be controlled by diet alone.

4.3 Contraindications

This medication is contra-indicated in the following cases:
hypersensitivity to gliclazide, other sulphonylureas, sulfonamides, or to any of the excipients;
type I diabetes, diabetic keto-acidosis, diabetic pre-coma and coma;
severe renal or hepatic impairment: in these cases the use of insulin is recommended;
treatment with miconazole (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions);
pregnancy and lactation (see Section 4.6 Fertility, Pregnancy and Lactation).

4.4 Special Warnings and Precautions for Use

Monitoring of diabetic state.

As with other antidiabetic therapies, patients must be under close medical supervision. Particular care must be taken during the initial period of stabilisation. Patients treated with gliclazide should be monitored regularly to ensure optimal control of the diabetic state and, where necessary, for adjustment of dosage.

Transferring to gliclazide.

Patients who have been previously treated with sulphonylureas or biguanides alone or in combination may be transferred to gliclazide. When gliclazide is administered as sole therapy to patients who have previously required combination therapy (e.g. biguanides and sulphonylureas), careful observation is essential during the transitional phase.
It is not generally recommended that insulin treated patients be transferred to gliclazide.

Patient awareness.

Comprehensive instructions must be given to the patient about the nature of the disease and what must be done to detect and prevent complications.

Acute complications such as severe trauma, fever, infection or surgery.

These acute complications provoke additional metabolic stress which accentuate the predisposition to hyperglycaemia and ketosis. Patients presenting with such conditions may require insulin to maintain control. It is not appropriate to increase the dosage of gliclazide.

Hypoglycaemia.

The risks of hypoglycaemia, together with its symptoms, treatment and conditions that predispose to its development, should be explained to the patient and to family members. The patient should be informed of the importance of following dietary advice, of taking regular exercise, and of regular monitoring of blood glucose levels.
Hypoglycaemia may occur following administration of sulphonylureas. Rarely cases may be severe and prolonged. This may involve hospitalisation and glucose infusion may need to be continued for several days.
Careful selection of patients and of the dose used, as well as provision of adequate information to the patient are necessary to avoid hypoglycaemic episodes. The following factors may increase the risk of hypoglycaemia:
patient does not follow the doctor's treatment advice (particularly elderly patients);
malnutrition;
irregular mealtimes, skipping meals, periods of fasting or dietary changes;
imbalance between physical exercise and carbohydrate intake;
renal impairment;
severe hepatic impairment;
overdose of anti-diabetic agents;
certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal impairment, concomitant administration of certain other medicines (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Gliclazide should only be prescribed if the patient is likely to have a regular food intake (including breakfast). It is important to have a regular carbohydrate intake due to the increased risk of hypoglycaemia if a meal is delayed, an inadequate amount of food is consumed or the food is low in carbohydrate. Hypoglycaemia is more likely to occur during periods of low-calorie diet, following prolonged or strenuous exercise, following alcohol intake or during treatment with a combination of hypoglycaemic agents.

Poor blood glucose control.

Blood glucose control in treated patients may be affected by St. John's wort (Hypericum perforatum) preparations (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions), fever, trauma, infection or surgical intervention. It may be necessary to discontinue treatment and to administer insulin in these cases.
The efficacy of oral antidiabetic agents often decreases in the long term. This may be due to progression in the severity of the diabetes, or to a reduced response to treatment. This phenomenon is known as secondary failure and should be distinguished from primary failure, when the drug is ineffective as first-line treatment. However, before classifying the patient as a secondary failure, dose adjustment and reinforcement of dietary measures should be considered.

Unstable blood glucose level (dysglycaemia).

Disturbances in blood glucose, including hypoglycaemia and hyperglycaemia have been reported, in diabetic patients receiving concomitant treatment with fluoroquinolones, especially in elderly patients. Indeed, careful monitoring of blood glucose is recommended in all patients receiving gliclazide and a fluoroquinolone at the same time.

Renal and hepatic impairment.

Severe renal or hepatic impairment may affect the distribution of gliclazide and hepatic impairment may also reduce the capacity for neoglucogenesis. These two effects increase the risk of severe hypoglycaemic reactions. A hypoglycaemic episode in these patients may be prolonged and appropriate management should be initiated.

Glucose-6-phosphate dehydrogenase deficiency (G6PD).

Treatment of patients with G6PD deficiency with sulphonylurea agents can lead to haemolytic anaemia. Since gliclazide belongs to the chemical class of sulphonylurea drugs, caution should be used in patients with G6PD deficiency and a nonsulphonylurea alternative should be considered.

Lactose intolerance.

Due to the presence of lactose, patients with rare hereditary problems of galactose intolerance, glucose-galactose malabsorption, or the Lapp lactase deficiency should not take this medicinal product.

Patients with porphyria.

Cases of acute porphyria have been described with the class of sulfonylurea drugs, in patients who have porphyria.

Use in elderly.

See Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties.

Paediatric use.

Not recommended for paediatric use, see Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

Glycated haemoglobin should be monitored regularly. Blood glucose measurement may also be useful.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Blood glucose monitoring during and after treatment is necessary when Glyade is used with medicines which can interact with gliclazide. It may also be necessary to adjust the dose of Glyade during and after treatment with such medicines.

1) The following medications are likely to increase the risk of hypoglycaemia.

Concomitant use which is contraindicated.

Miconazole (systemic route, oromucosal gel).

Increases the hypoglycaemic effect with possible onset of hypoglycaemia symptoms, or even coma.

Concomitant use which is not recommended.

Phenylbutazone (systemic route).

Increases the hypoglycaemic effect of sulphonylureas (displaces their binding to plasma proteins and/or reduces their elimination). It is preferable to use a different anti-inflammatory agent, or else to warn the patient and emphasise the importance of self-monitoring. Where necessary, adjust the dose during and after treatment with the anti-inflammatory agent.

Alcohol.

Acute alcohol intoxication potentiates the hypoglycaemic action of all sulphonylurea agents by inhibiting compensatory reactions. This can lead to the onset of hypoglycaemic coma. Ingestion of alcohol may also cause a disulfiram-like reaction with characteristic flushing of the face, throbbing headache, giddiness, tachypnoea, tachycardia or angina pectoris. Chronic alcohol abuse may, as a result of liver enzyme induction, increase the metabolism of sulphonylurea drugs, shortening the plasma half-life and duration of action.
Avoid alcohol or medicines containing alcohol.

Concomitant use which requires special care.

Potentiation of the blood glucose lowering effect and therefore in some instances, hypoglycaemia may occur when one of the following medications is taken.

Other antidiabetic agents (insulins, acarbose, biguanides, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, GLP-1 receptor agonists), sulfonamides, clarithromycin, clofibrate, salicylates (high doses), chloramphenicol, MAOIs, β-blockers, H2-receptor antagonists, ACE inhibitors, fluconazole and nonsteroidal anti-inflammatory agents.

2) The following medications may cause an increase in blood glucose levels.

Advise the patient and emphasise the importance of glucose monitoring.

Concomitant use which is not recommended.

Danazol.

If the use of danazol cannot be avoided, it may be necessary to adjust the dose of Glyade during and after treatment with danazol.

Concomitant use which requires special care.

Chlorpromazine.

High doses (> 100 mg per day of chlorpromazine) can increase blood glucose levels (reduced insulin release). Advise the patient and emphasise the importance of glucose monitoring. It may be necessary to adjust the dose of Glyade during and after treatment with chlorpromazine.

Glucocorticoids (systemic and local route: intra-articular, cutaneous and rectal preparations) and tetracosactrin.

Concomitant use may increase blood glucose levels with possible ketosis (glucocorticoids cause reduced tolerance to carbohydrates). Emphasise the importance of blood glucose monitoring, particularly at the start of treatment. It may be necessary to adjust the dose of Glyade during and after treatment with glucocorticoids.

Salbutamol, terbutaline (intravenous).

May cause increased blood glucose levels due to beta-2 agonist effects. If necessary, switch to insulin.

Barbiturates, oestrogens and progestogens.

May adversely affect blood sugar control with hypoglycaemic agents in some patients by causing increased blood glucose levels.

St. John's wort (Hypericum perforatum) preparations.

Gliclazide exposure is decreased by St. John's wort (Hypericum perforatum).

3) The following products may cause unstable blood glucose.

Concomitant use which requires special care.

Fluoroquinolones.

In case of a concomitant use of gliclazide and a fluoroquinolone, the patient should be warned of the risk of unstable blood glucose, and the importance of blood glucose monitoring should be emphasised.

Concomitant use to be taken into consideration.

Anticoagulant therapy (warfarin).

Sulphonylureas may lead to potentiation of anticoagulation during concurrent treatment. Adjustment of warfarin may be necessary.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
In animal studies embryo-toxicity and/or birth defects have been demonstrated with some sulfonylureas.
Gliclazide should not be used in pregnant women. From a clinical point of view, there are limited data (less than 300 pregnancies) to allow evaluation of the possible malformative or foetotoxic effects of gliclazide, when administered during pregnancy. Animal studies of gliclazide have not shown any teratogenic effect.
Glyade is contraindicated during pregnancy and insulin is the drug of first choice for treatment of diabetes during pregnancy. Treatment should be changed from Glyade to insulin therapy before pregnancy is attempted, or as soon as pregnancy is discovered. Control of diabetes should be achieved before the time of conception to reduce the risk of congenital abnormalities linked to uncontrolled diabetes.
It is not known whether gliclazide or its metabolites are excreted in breast milk. Given the risk of neonatal hypoglycaemia, Glyade is contraindicated in women who are breastfeeding. A risk to newborns/infants cannot be excluded.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.
Adverse reactions have occurred in some 12% of cases in clinical studies. However, approximately 2% of patients were withdrawn from therapy because of adverse reactions, notably hypoglycaemia, gastrointestinal disturbances (constipation, nausea, epigastric discomfort and heartburn), dermatological reactions (rash and transient itching), and biochemical abnormalities (elevated serum creatinine, increased serum alkaline phosphatase, raised serum AST, elevated BUN and raised serum bilirubin). Headache, slight disulfiram-like reactions and lassitude have also been reported.
Serious reactions which have been reported with other sulphonylureas are leucopenia, thrombocytopenia, agranulocytosis, pancytopenia, haemolytic anaemia, cholestatic jaundice and gastrointestinal haemorrhage. These reactions have not been reported with gliclazide.

Hypoglycaemia (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

The most frequent adverse reaction with gliclazide is hypoglycaemia.
As is the case with all sulphonylurea drugs, hypoglycaemic reactions have been reported following gliclazide administration. However, a number of studies have shown that hypoglycaemia is less common with gliclazide than with glibenclamide.
Possible symptoms of hypoglycaemia are: headache, intense hunger, nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor concentration, reduced awareness and slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of powerlessness, loss of self-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness, possibly resulting in coma and/or death. In addition, signs of adrenergic counter-regulation may be observed: sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia.
Usually, symptoms disappear after intake of carbohydrate such as sugar (artificial sweeteners have no effect). Experience with other sulphonylureas shows that hypoglycaemia can recur even when these measures are initially effective. If a hypoglycaemic episode is severe or prolonged, and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalisation is required.
Severe hypoglycaemia, though very rarely reported, may occur in patients receiving gliclazide.

Other adverse effects reported with gliclazide.

Gastrointestinal disturbances (reported with gliclazide), including nausea, dyspepsia, diarrhoea, abdominal pain, vomiting and constipation may be avoided or minimised if gliclazide is taken with breakfast.
The following adverse effects have been rarely reported.

Skin and subcutaneous tissue disorders.

Pruritus, urticaria, maculopapular rashes, rash, angioedema, erythema and bullous reactions (such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) (as with other sulfur-containing medications) and autoimmune bullous disorders and exceptionally, drug rash with eosinophilia and systemic symptoms (DRESS).

Blood and lymphatic system disorders (as with other sulphonylurea medications).

Anaemia, leucopenia, thrombocytopenia and agranulocytosis. These are in general reversible upon discontinuation of medication.

Hepatobiliary disorders.

Elevations of serum bilirubin and hepatic enzymes (AST, ALT, alkaline phosphatase) levels, and exceptionally, hepatitis (isolated reports). Treatment should be discontinued if cholestatic jaundice appears. These symptoms usually disappear after discontinuation of treatment.

Investigations.

Occasional elevations of serum creatinine, blood urea nitrogen.

Eye disorders.

Transient visual disturbances may occur due to changes in blood glucose levels, particularly on initiation of treatment.
As with any glucose-lowering medication, transient visual disturbances may occur on initiation of treatment due to changes in blood glucose levels.

Class effects.

The following adverse events have been observed with sulphonylureas: cases of erythrocytopenia, agranulocytosis, haemolytic anaemia, pancytopenia and allergic vasculitis, hyponatremia, elevated liver enzyme levels and even impairment of liver function (e.g. with cholestasis and jaundice) and hepatitis which regressed after withdrawal of the sulphonylurea or led to life-threatening liver failure in isolated cases.

4.2 Dose and Method of Administration

For adult use only.
Glyade should be taken with food because there is increased risk of hypoglycemia if a meal is taken late, if an inadequate amount of food is consumed or if the food is low in carbohydrate. It is recommended that the medication be taken at breakfast time. If a dose is forgotten, the dose taken on the next day should not be increased.
The daily dose may vary from 40 to 320 mg taken orally. The initial recommended dose is 40 mg (half tablet) daily, even in elderly patients (≥ 65 years) and may be increased if necessary up to 320 mg (four tablets) daily. Doses up to 160 mg daily may be taken in a single dose but preferably at the same time each morning. Doses in excess of 160 mg should be taken in divided doses in the morning and evening.
In general, the dosage will depend on the severity of the glycaemia with ongoing adjustments made in order to obtain the optimal response at the lowest dosage.
Treatment with gliclazide does not obviate the necessity of maintaining standard dietary regulations.

4.7 Effects on Ability to Drive and Use Machines

Patients should be made aware of the symptoms of hypoglycaemia and should be careful if driving or operating machinery, especially at the beginning of treatment.

4.9 Overdose

Advice on overdose management can be obtained from the national Poisons Information Centre by telephoning 131126.
Overdose of sulphonylureas may cause hypoglycaemia.
Moderate symptoms of hypoglycaemia (without loss of consciousness or neurological signs) should be corrected by carbohydrate intake, dose adjustment and/or modification of diet. Strict monitoring should be continued until the doctor is sure that the patient is out of danger.
Severe hypoglycaemic reactions are possible (with coma, convulsions or other neurological disorders) and must be treated as a medical emergency, requiring immediate hospitalisation.
If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid I.V. injection of 50 mL of concentrated glucose solution (20 to 30%). This should be followed by continuous infusion of a more dilute glucose solution (10%) at a rate necessary to maintain blood glucose levels above 5 mmol/L. It is recommended that patients should be monitored closely for a 48 hour period at least.
Plasma clearance of gliclazide may be prolonged in patients with hepatic disease. However, due to the strong binding of gliclazide to proteins, dialysis is not effective in these patients.

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose monohydrate, magnesium stearate, maize starch, pregelatinised maize starch, purified talc.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Glyade tablets are supplied in aluminium/PVC blister strips containing 100 tablets enclosed in an outer carton.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes