Consumer medicine information

Daonil; (DAY-o(h)-nill)

Glibenclamide

BRAND INFORMATION

Brand name

Daonil

Active ingredient

Glibenclamide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Daonil; (DAY-o(h)-nill).

What is in this leaflet

This leaflet answers some common questions about Daonil. It does not contain all the available information. It 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 Daonil 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 Daonil is used for

Daonil is used to control blood glucose levels in patients with type 2 diabetes mellitus. This type of diabetes is also known as non-insulin-dependent diabetes (NIDDM) or maturity onset diabetes.

Daonil is used in conjunction with diet control and exercise to control blood sugar.

Daonil can be used alone, or in combination with insulin or other anti-diabetes medicines.

Daonil lowers high blood glucose by increasing the amount of insulin released by your pancreas.

Daonil belongs to a group of medicines called sulphonylureas.

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 your heart, eyes, circulation or kidneys.

Low blood glucose can occur suddenly. Signs may include:

  • weakness, trembling, shaking
  • sweating
  • light headedness, dizziness, headache or lack of concentration
  • tearfulness, crying or depression
  • irritability
  • hunger
  • numbness around the lips and tongue
  • restlessness or disturbed sleep

If not treated promptly, these may progress to:

  • loss of co-ordination
  • slurred speech
  • confusion
  • loss of consciousness or seizures

High blood glucose usually occurs more slowly than low blood glucose. Signs of high blood glucose may include:

  • lethargy or tiredness
  • headache
  • severe thirst
  • passing large amounts of urine and more often
  • blurred vision
  • dry mouth or dry skin

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

Daonil is not addictive.

Daonil is available only with a doctor's prescription.

This medicine is not expected to affect your ability to drive a car or operate machinery.

There is not enough information to recommend the use of this medicine for children.

Before you take Daonil

When you must not take it

Do not take Daonil if you have an allergy to:

  • any medicine containing glibenclamide
  • any of the ingredients listed at the end of this leaflet.
  • any other similar medicines (such as sulphur antibiotics or sulphonylureas).

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take Daonil if you have any of the following conditions:

  • type 1 diabetes mellitus (insulin-dependent diabetes mellitus, also known as IDDM, or juvenile or growth onset diabetes)
  • unstable diabetes
  • diabetic ketoacidosis
  • diabetic coma or pre-coma
  • severe kidney disease
  • severe liver disease
  • you are being treated with the medication bosentan

Do not take this medicine if you are pregnant.

It may affect your developing baby if you take it during pregnancy.

Insulin is more suitable for controlling blood sugar during pregnancy. Your doctor will replace Daonil with insulin while you are pregnant.

Do not breast-feed if you are taking this medicine. It is not known if Daonil passes into breast milk. Daonil should not be taken while you are breastfeeding.

Do not give Daonil to children. Safety and effectiveness in children has not been established.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

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

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • glucose-6-phosphate (G6PD) deficiency
  • a history of diabetic coma
  • adrenal, pituitary (or thyroid) problems
  • heart failure
  • kidney or liver problems
  • you drink alcohol in any amount
  • you do not eat regular meals
  • you do a lot of exercise or heavy work
  • you are feeling ill or unwell
  • you are taking any other antidiabetic treatment

Diet, exercise, alcohol and your general health all strongly affect the control of your diabetes. Discuss these things with your doctor.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start taking Daonil.

Taking other medicines

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

Some medicines may lead to low blood glucose (hypoglycaemia) by increasing the blood glucose lowering effect of Daonil. These include:

  • alcohol
  • some medicines used to treat high blood pressure
  • some medicines used to treat arthritis, pain and inflammation
  • (anabolic) steroids
  • some cholesterol-lowering medicines
  • other medicines used to treat diabetes
  • some antibiotics
  • medicines used to prevent blood clots
  • disopyramide, a medicine used to treat irregular heart rhythms
  • some medicines used to treat depression
  • pentoxifylline (oxpentifylline), a medicine used to treat blood vessel problems
  • some medicines used to treat cancer
  • some medicines used to treat gout
  • cimetidine and ranitidine, medicines used to treat reflux and ulcers

Some medicines may lead to loss of control of your diabetes (resulting in high blood glucose) by weakening the blood glucose-effect of Daonil. These include:

  • alcohol
  • some medicines used to treat glaucoma
  • some medicines used to treat high blood pressure
  • corticosteroids such as prednisone and cortisone
  • glucagon, a medicine used to treat low blood glucose
  • some medicines used to treat tuberculosis
  • high dose nicotinic acid used for the lowering of blood fats
  • oestrogens and oral contraceptives
  • some medicines used to treat mental illness or psychotic disorders
  • phenytoin, a medicine used to treat epilepsy (convulsions)
  • cimetidine and ranitidine, medicines used to treat reflux and ulcers
  • ritodrine, a medicine used to prevent premature labour
  • diuretics, also known as fluid tablets
  • some asthma medicines, preparations for coughs and colds and weight reducing medicines
  • thyroid hormones
  • large doses of laxatives
  • indomethacin, a medicine used to treat arthritis (an inflammatory condition)
  • barbiturates, medicines used for sedation

Some medicines may hide the symptoms of low blood sugar (hypoglycaemia). These include:

  • alcohol
  • some medicines used to treat high blood pressure

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 Daonil.

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

How to take Daonil

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

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

How much to take

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

How to take it

Swallow the tablets with a full glass of water.

When to take it

Take your tablet immediately before breakfast. If you only eat a very light breakfast, then this dose should be put off until lunchtime.

Do not skip meals whilst using Daonil. Take your dose at the same time each day.

How long to take it

Continue taking Daonil for as long as your doctor tells you.

This medicine helps to control your diabetes, but will not cure it. Therefore you may have to take it for a long time. It is important to keep taking your medicine even if you feel well. Make sure you have enough Daonil to last over weekends and holidays.

If you forget to take it

If it 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 soon as you remember, and then go back to taking your medicine as you would normally.

Missed doses can cause high blood sugar (hyperglycaemia).

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

If you are not sure what to do, ask your doctor, pharmacist or diabetes educator.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Daonil. Do this even if there are no signs of discomfort or poisoning.

If you take too much Daonil you may experience symptoms of hypoglycaemia (low blood sugar).

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

At the first signs of hypoglycaemia, raise your blood glucose quickly by taking jelly beans, sugar or honey, soft drink (non-diet) or glucose tablets.

If you experience any of the symptoms of an overdose, immediately get medical help.

While you are using Daonil

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Daonil.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant while taking Daonil, tell your doctor immediately.

Make sure you, your friends, family and work colleagues can recognise the symptoms of hypoglycaemia and hyperglycaemia and know how to treat them.

If you experience any of the symptoms of low blood sugar (hypoglycaemia), you need to raise your blood glucose urgently. You can do this by taking one of the following:

  • 5 - 7 jelly beans
  • 3 teaspoons of sugar or honey
  • 1/2 can of ordinary (non-diet) soft drink
  • 2-3 concentrated glucose tablets

Unless you are within 10 to 15 minutes of your next meal or snack, follow up with extra carbohydrates eg. plain biscuits, fruit or milk - when over the initial symptoms. Taking this extra carbohydrate will prevent a second drop in your blood glucose level.

If you are elderly or are taking other medicines for diabetes such as insulin or metformin, the risk of hypoglycaemia is increased.

The risk of hypoglycaemia is also increased in the following situations:

  • too much Daonil
  • too much or unexpected exercise
  • delayed meal or snack
  • too little food

If you experience any of the signs of high blood glucose (hyperglycaemia), contact your doctor immediately.

The risk of hyperglycaemia is increased in the following situations:

  • undiagnosed or uncontrolled diabetes
  • illness, infection or stress
  • too little Daonil
  • certain other medicines
  • too little exercise
  • eating more carbohydrates than normal

If you become ill or experience extra stress, injury, fever, infection or need surgery, tell your doctor.

Your blood glucose may become difficult to control at these times. Your doctor may decide to change your treatment and use insulin instead of Daonil.

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.

Visit your doctor for regular checks of your eyes, feet, kidneys, heart, circulation, blood and blood pressure.

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

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

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

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

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

Things you must not do

Do not take Daonil to treat any other complaints unless your doctor tells you to.

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

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Do not skip meals while taking Daonil.

Things to be careful of

Protect your skin when you are in the sun, especially between 10am and 3pm.

Daonil 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 severe sunburn.

If outdoors, wear protective clothing and use a highly effective sunscreen. If you experience sunburn, tell your doctor immediately.

If you have to be alert, for example when driving, be especially careful not to let your blood glucose levels fall too low.

Low blood glucose levels may slow your reaction time and affect your ability to drive or operate machinery. Drinking alcohol can make this worse. However, Daonil by itself is unlikely to affect how you drive or operate machinery.

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 eg. sugar sachets or jelly beans
  • carry emergency food rations in case of a delay eg. dried fruit, biscuits or muesli bars
  • keep some Daonil readily available

If you become sick with a cold, fever or flu, it is very important to continue taking Daonil. 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

Tell your doctor, or pharmacist as soon as possible if you do not feel well while you are taking Daonil.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

The following possible side effect lists are placed in order of increasing urgency of the behaviour required.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • signs of hypoglycaemia which may include weakness, trembling or shaking, sweating, light headedness, headache, dizziness, lack of concentration, tearfulness or crying, irritability, hunger and numbness around the lips and fingers
  • stomach upset including nausea (feeling sick), vomiting, heartburn, indigestion, cramps
  • diarrhoea, constipation or a feeling of fullness in the stomach
  • loss of appetite
  • headache
  • weakness
  • eye problems including blurred or double vision
  • unusual weight gain

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • deafness
  • severe pain or tenderness in the stomach
  • sudden onset of abnormal thoughts or delusions
  • rash, sores, redness or itching of the skin, itchy hives-like rash or spots
  • symptoms of sunburn such as redness, itching, swelling or blistering which may occur more quickly than normal
  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin
  • symptoms of lactic acidosis (too much acid in the blood) which may include loss of appetite, unexplained weight loss, nausea, vomiting, stomach pain, trouble breathing, feeling weak, tired or uncomfortable, unusual muscle pain, slow heart beat
  • yellowing of the skin or eyes, also called jaundice
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • signs of anaemia such as tiredness, being short of breath and looking pale
  • a change in colour or amount of urine passed, blood in the urine

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • blindness
  • convulsions or fits
  • swelling of the face, lips or tongue which may cause difficulty in breathing

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After using Daonil

Storage

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they may not keep as well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store Daonil or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. 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 this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Daonil 5 mg tablets are white, biplane oblong tablets with a score-line on both sides. LDI is engraved each side of the score-line and inverted. The other side is plain.

Ingredients

Daonil contains 5 mg of glibenclamide as the active ingredient.

Inactive ingredients:

  • lactose monohydrate
  • maize starch
  • pre-gelatinised maize starch
  • purified talc
  • colloidal anhydrous silica
  • magnesium stearate

This medicine does not contain sucrose, tartrazine or any other azo dyes.

Manufacturer/Sponsor

Daonil is supplied in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall No: 1800 818 806

Daonil is supplied in New Zealand by:

sanofi-aventis new zealand limited
Level 8, 56 Cawley Street
Ellerslie, Auckland
New Zealand
Freecall No: 0800 283 684

This leaflet was prepared in August 2016.

Australian Registration Number:
AUST R 73683

Daonil is a registered trademark of sanofi-aventis

daonil-ccdsv10-cmiv9-aug16

Published by MIMS February 2017

BRAND INFORMATION

Brand name

Daonil

Active ingredient

Glibenclamide

Schedule

S4

 

1 Name of Medicine

Glibenclamide.

2 Qualitative and Quantitative Composition

Daonil.

Each tablet contains 5 mg of glibenclamide.
Excipients of known effect: Lactose monohydrate.

Semi-Daonil*.

Each tablet contains 2.5 mg of glibenclamide.
Excipients of known effect: Lactose monohydrate.
*Not marketed.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Uncoated tablets.

Daonil.

White, biplane oblong tablet with a score-line on both sides. LDI is engraved each side of the score-line and inverted. The other side is plain.

Semi-Daonil*.

White, round, biplanar tablet with beveled edge, Hoechst logo and LDY on either side of score line.
*Not marketed.

4 Clinical Particulars

4.1 Therapeutic Indications

Daonil and Semi-Daonil are indicated as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (type 2) whose hyperglycaemia cannot be controlled by diet alone. Because of its broad and predictable action, Daonil and Semi-Daonil are often suitable for the management of patients who have failed to respond to other oral antidiabetics.
In initiating treatment for noninsulin dependent diabetes, diet should be emphasised as the primary form of treatment. Caloric restriction and weight loss are essential in the obese diabetic patient. Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycaemia. The importance of regular physical activity should also be stressed and cardiovascular risk factors should be identified and corrective measures taken where possible. If this treatment programme fails to reduce symptoms and/or blood glucose, the use of an oral sulphonylurea should be considered. Use of Daonil and Semi-Daonil must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitute for diet or as a convenient mechanism for avoiding dietary restraint.

4.2 Dose and Method of Administration

Dosage of glibenclamide must be based on regular blood and urine glucose determinations and must be carefully individualised to obtain optimum therapeutic effect. The dosage of glibenclamide must be the lowest possible dose which is effective. If appropriate glibenclamide dosage regimens are not followed, hypoglycaemia may be precipitated. It is very important not to skip meals after the tablets have been taken.
In newly treated patients with diabetes, stabilisation should be commenced with one Semi-Daonil tablet daily, taken immediately before breakfast. Patients who eat only a light breakfast should defer the first dose of the day until lunchtime.
After 3-5 days, the blood sugar and urine sugar should be checked. If good control has been achieved, the daily dose of one Semi-Daonil tablet is continued as maintenance therapy.
If control is unsatisfactory, elevation of the daily dose in steps of 2.5 mg is necessary, at intervals of 7 days, up to a maximum of 15 mg or, in exceptional cases, 4 tablets (20 mg) daily.
Daily allotments of up to 10 mg can be taken as a single dose before breakfast; daily dosage in excess of 10 mg should be taken before the evening meal.
As an improvement in control of diabetes is, in itself, associated with higher insulin sensitivity, glibenclamide requirements may fall as treatment proceeds. To avoid hypoglycaemia, timely dose reduction or cessation of Daonil therapy must therefore be considered.
Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose. Measures for dealing with such mistakes (in particular forgetting a dose or skipping a meal), or in the event a dose cannot be taken at the prescribed time, must be discussed and agreed between physician and patient beforehand.
In the management of type 2 diabetes mellitus, oral hypoglycaemic administration is not a substitute for appropriate dietary control.
When transferring patients from other oral antidiabetic drugs, it is recommended to begin with the usual starting dose (2.5 to 5 mg) per day. Depending on the pharmacokinetic and pharmacodynamic characteristics of the previous medication, a drug free transition period may be necessary in order to avoid overlapping drug effects, possibly resulting in hypoglycaemia.
In general, patients who were previously maintained on insulin dosages up to 40 units daily may be transferred directly to glibenclamide and administration of insulin may be abruptly discontinued; the initial glibenclamide dosage is 2.5-5 mg daily in patients whose insulin dosage was less than 20 units daily and 5 mg daily in patients whose insulin dosage was 20-40 units daily. In patients requiring insulin dosages greater than 40 units daily, an initial glibenclamide dosage of 5 mg daily should be started and insulin dosage reduced by 50%. Subsequently, insulin is withdrawn gradually and dosage of glibenclamide is increased in increments of 1.25-2.5 mg daily every 2-10 days, according to the patient's tolerance and therapeutic response. During the period of insulin withdrawal, patients should test their urine at least 3 times daily for glucose and acetone, and should be instructed to report the results to their physician so that appropriate adjustments in therapy may be made if necessary; when feasible, patient or laboratory monitoring of blood glucose concentration is preferable. The presence of persistent ketonuria with glycosuria, ketosis and/or inadequate lowering or persistent elevation of blood glucose concentration indicates that the patient requires insulin therapy.
If adequate control is no longer possible with diet and Daonil and Semi-Daonil (maximum 20 mg daily), good results may be obtained by combined administration of Daonil and a biguanide derivative.

4.3 Contraindications

1. Known hypersensitivity or allergy to glibenclamide or any of the excipients.
2. Insulin dependent diabetes (type 1 or juvenile onset diabetes) or in those with diabetes complicated by ketosis.
3. Treatment of diabetic ketoacidosis.
4. Serious metabolic decompensation with acidosis, in particular precoma and coma.
5. Severe impairment of renal function.
6. Severe hepatic dysfunction.
7. Pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
8. Lactation (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation).
9. Patients treated with bosentan (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

The treatment of diabetes requires regular checks. Until optimal control is achieved or when changing from one product to another or when tablets are not taken regularly, the patient's alertness and capacity to react may be impaired to such an extent that he or she may not be fit to drive or to operate machinery.
When situations of unusual stress arise (e.g. trauma, emergency or elective surgery, febrile infections), blood glucose regulation may deteriorate and a temporary change to insulin may become necessary to maintain good metabolic control.
It should be borne in mind that there is a possibility of cross sensitivity to sulphonamides and their derivatives. Persons allergic to other sulphonamide derivatives may develop an allergic reaction to glibenclamide as well.
Epidemiological studies suggest that the administration of glibenclamide is associated with an increased risk of cardiovascular mortality, when compared to treatment with metformin or gliclazide. This risk was especially observed in patients with diagnosed coronary diseases.

Hypoglycaemic reactions.

Severe hypoglycaemia, which may be prolonged and is potentially lethal, can be induced by all sulphonylureas.
Debilitated, malnourished or geriatric patients and patients with mild disease or impaired hepatic or renal function should be carefully monitored and dosage of glibenclamide should be carefully adjusted in these patients, since they may be predisposed to developing hypoglycaemia. Renal or hepatic insufficiency may cause increased serum concentrations of glibenclamide and hepatic insufficiency may also diminish gluconeogenic capacity, both of which increase the risk of severe hypoglycaemic reactions.
Alcohol ingestion (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions), intense or prolonged exercise, deficient caloric intake, use of more than one antidiabetic agent, severe endocrine disorders and adrenal or pituitary insufficiency may also predispose patients to the development of hypoglycaemia.
If risk factors for hypoglycaemia are present, it may be necessary to adjust the dosage of glibenclamide or the entire therapy. This also applies whenever illness occurs during therapy or the patient's lifestyle changes.
Elderly patients are particularly susceptible to hypoglycaemic action of glucose lowering drugs. Hypoglycaemia may be difficult to recognise in the elderly. The initial and maintenance dosing should be conservative to avoid hypoglycaemic reactions.
Hypoglycaemia can, almost always, be promptly controlled by immediate intake of carbohydrates (glucose or sugar, e.g. in the form of sugar lumps, sugar sweetened fruit juice or tea).
Despite initially successful countermeasures, hypoglycaemia may recur. Patients must, therefore, remain under close observation.
Severe hypoglycaemia, or a protracted episode, which can only be temporarily controlled by usual amounts of sugar, further requires immediate treatment and follow-up by a physician and, in some circumstances, in-patient hospital care.
Patients receiving glibenclamide should be monitored with regular clinical and laboratory evaluations, including blood and urine glucose determinations, to determine the minimum effective dosage and to detect primary failure (inadequate lowering of blood glucose concentration at the maximum recommended dosage) or secondary failure (loss of control of blood glucose concentration following an initial period of effectiveness) to the drug. Glycosylated haemoglobin measurements may also be useful for monitoring the patient's response to glibenclamide therapy. During the withdrawal period in patients in whom glibenclamide is replacing insulin, patients should be instructed to test their urine for glucose and ketones at least 3 times daily, and to report the results to their physician; when feasible, patient or laboratory monitoring of blood glucose concentration is preferable. Care should be taken to avoid ketosis, acidosis and coma during the withdrawal period in patients being switched from insulin to glibenclamide. If adequate lowering of blood glucose concentration is no longer achieved during maintenance therapy with glibenclamide, the drug should be discontinued.
As is necessary during treatment with any blood glucose lowering drug, the patient and the physician must be aware of the risk of hypoglycaemia. Patients and responsible family members should be made aware of the signs and symptoms of hyperglycaemia and hypoglycaemia and the prompt action required in the event of such occurrences. Symptoms of hyperglycaemia include severe thirst, dry mouth, frequent micturition and dry skin. Possible symptoms of hypoglycaemia include intense hunger, nausea, vomiting, sweating, tremor, pareses, sensory disturbances, restlessness, irritability, aggressiveness, depression, confusion, speech disorders, aphasia, visual disorders, impaired concentration, impaired alertness and reactions, headaches, dizziness, disturbed sleep, helplessness, loss of self control, delirium, transient neurological disorders such as cerebral convulsions, lassitude, sleepiness, somnolence, loss of consciousness up to and including coma, shallow respiration and bradycardia. In addition, signs of adrenergic counter-regulation may be present, such as sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmias.
The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke. The symptoms of hypoglycaemia nearly always subside when hypoglycaemia is corrected.
In the presence of a genetic defect in metabolism, the elimination half-life may be prolonged.
Because of its broad and predictable hypoglycaemic effect, Daonil and Semi-Daonil should be taken immediately before breakfast. Patients who eat only a light breakfast should defer the first dose of the day until lunchtime.
Some improvement in glucose tolerance may take place after a few weeks treatment with Daonil and Semi-Daonil. The clinical status should be checked within the first 4-8 weeks and at regular intervals thereafter, so as to ascertain whether it is possible to cut down the dose or cease glibenclamide therapy. Correction of dosage must also be considered whenever the patient's weight changes, the patient's lifestyle changes or other factors arise that cause an increased susceptibility to hypoglycaemia or hyperglycaemia.

Haemolytic anaemia.

Treatment of patients with glucose-6-phospate dehydrogenase (G6PD) deficiency with sulphonylurea agents can lead to haemolytic anaemia. Since glibenclamide belongs to the class of sulphonylurea agents, caution should be used in patients with G6PD-deficiency and a nonsulphonylurea alternative should be considered.

Use in hepatic impairment.

See Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemic reactions.

Use in renal impairment.

See Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemic reactions.

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemic reactions.

Paediatric use.

The safety and efficacy of glibenclamide in children have not been established. Glibenclamide is not recommended for use in this age group.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

An increased incidence of elevated liver enzymes was observed in patients receiving glibenclamide concomitantly with bosentan. Both bosentan and glibenclamide inhibit the bile salt export pump, leading to intracellular accumulation of cytotoxic bile salts. Therefore, this combination should not be used (see Section 4.3 Contraindications).
Other drugs given at the same time as sulphonylureas may cause undesirable depression or elevation of the blood sugar level.
Glibenclamide is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. This should be taken into account when glibenclamide is coadministered with inducers or inhibitors of CYP2C9.
Drugs which may potentiate the hypoglycaemic action of Daonil and Semi-Daonil include insulin, other oral antidiabetic agents, alcohol, ACE inhibitors, aminosalicylic acid, anabolic steroids and male sex hormones, azapropazone, beta-receptor blockers, bezafibrate, biguanides, chloramphenicol, clarithromycin, clofibrate, clonidine, co-trimoxazole, coumarin derivatives, cyclophosphamide monohydrate, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, gemfibrozil, guanethidine, heparin, ifosfamide, MAO inhibitors, miconazole, pentoxifylline (oxpentifylline) (parenteral, in high doses), oxyphenbutazone, para-aminosalicylic acid, phenylbutazone, phenyramidol, phosphamides, probenecid, quinolone antibiotics, ranitidine, reserpine, salicylates, sulphinpyrazone, certain long acting sulphonamides, tetracycline compounds, tritoqualine and trophosphamide. Highly protein bound drugs which may also potentiate the hypoglycaemic action of Daonil and Semi-Daonil due to glibenclamide displacement from plasma proteins include oral anticoagulants, hydantoins, salicylates and other nonsteroidal anti-inflammatory agents.
Drugs which may cause an attenuation of the hypoglycaemic action of Daonil and Semi-Daonil include adrenaline (epinephrine) and other sympathomimetic agents, alcohol, acetazolamide, barbiturates, calcium channel blockers, cimetidine, clonidine, corticosteroids, diazoxide, diuretics, glucagon, isoniazid, large doses of laxatives, nicotinic acid (high dosage), oestrogens, progestogens, phenothiazine derivatives, phenytoin, ranitidine, rifampicin, ritodrine and thyroid hormones.
Concomitant treatment with beta-receptor blockers, clonidine, reserpine, guanethidine or other sympatholytic drugs may mask the warning symptoms of a hypoglycaemic attack. The symptoms of hypoglycaemia may also be milder or absent where hypoglycaemia develops gradually or where there is autonomic neuropathy. In rare instances, potentiation or attenuation of the blood sugar lowering effect of Daonil and Semi-Daonil have been observed during concomitant treatment with H2-receptor antagonists clonidine or reserpine.
In very rare cases, an intolerance to alcohol may occur. Both acute and chronic alcohol intake or excessive alcohol ingestion by people who drink occasionally, may attenuate the hypoglycaemic effect of glibenclamide or dangerously potentiate it by delaying its metabolic inactivation. Disulfiram-like reactions have occurred very rarely following the concomitant use of alcohol and glibenclamide.
Glibenclamide may either potentiate or weaken the effect of coumarin derivatives.
Glibenclamide may increase ciclosporin plasma concentration and potentially lead to its increased toxicity. Monitoring and dosage adjustment of ciclosporin are, therefore, recommended when both drugs are coadministered.
Colesevelam binds to glibenclamide and reduces glibenclamide absorption from the gastrointestinal tract. No interaction was observed when glibenclamide was taken at least 4 hours before colesevelam. Therefore glibenclamide should be administered at least 4 hours prior to colesevelam.
Food does not alter the bioavailability or other pharmacokinetic parameters of glibenclamide.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
It is important to achieve strict normoglycaemia during pregnancy. Glibenclamide must not be taken during pregnancy. The patient must change over to insulin during pregnancy. The sulphonylureas may enter the foetal circulation and cause neonatal hypoglycaemia. In animal studies, embryotoxicity and/or birth defects have been demonstrated.
Patients planning a pregnancy must inform their physician. It is recommended that such patients change to insulin.
Category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Relevant texts should be consulted for further details.
 It is not known whether glibenclamide is excreted in milk or whether it has a harmful effect on the newborn. To prevent possible ingestion with breast milk, glibenclamide must not be taken by breastfeeding women. If necessary, the patient must change over to insulin or must stop breastfeeding.

4.7 Effects on Ability to Drive and Use Machines

See Section 4.4 Special Warnings and Precautions for Use.

4.8 Adverse Effects (Undesirable Effects)

Clinical experience in the use of Daonil and Semi-Daonil has shown that side effects serious enough to compel discontinuation of therapy are uncommon, even during long-term therapy. However, if adverse effects persists, the drug should be discontinued.

Hypoglycaemia.

Hypoglycaemia may not only be severe, but also prolonged and fatal (see Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemic reactions; Section 4.9 Overdose).

Eye disorders.

Especially at the start of treatment, there may be temporary visual impairment due to the change in blood glucose levels. The cause is a temporary alteration in the turgidity and hence, the refractive index of the lens, this being dependent on blood glucose level.

Gastrointestinal reactions.

Adverse gastrointestinal effects, such as nausea, vomiting, epigastric fullness or sensation of pressure, abdominal pain, anorexia, heartburn, dyspepsia and diarrhoea, are the most common adverse reactions to glibenclamide, occurring in about 1-2% of patients. Glibenclamide induced adverse gastrointestinal effects appear to be dose related and may subside following a reduction in dosage. Pancreatitis has been reported rarely.

Dermatologic reactions.

Hypersensitivity reactions, allergic or pseudoallergic reactions may occur. Allergic skin reactions, e.g. pruritus, erythema, urticaria, erythematous and maculopapular and bullous skin eruptions or psoriasiform drug eruptions, occur in 1.5% of treated patients. These may be transient and may disappear despite continued use of glibenclamide; if skin reactions persist, the drug should be discontinued. In isolated cases, mild reactions in the form of urticaria may develop into serious and even life threatening reactions with dyspnoea and fall in blood pressure, sometimes progressing to shock. In the event of urticaria, a physician must, therefore, be notified immediately.
A hypersensitivity reaction may be directed against glibenclamide itself, but may alternatively be triggered by excipients. Allergy to sulphonamide derivatives may also be responsible for an allergic reaction to glibenclamide.
In isolated cases, allergic vasculitis may arise and, in some circumstances, may be life threatening. In isolated cases, hypersensitivity of the skin to light may occur and sodium concentration in the serum may decrease. Porphyria cutanea tarda and pellagra-like changes have been reported with sulphonylureas.

Haematologic reactions.

Anaemia, leukopaenia, thrombocytopaenia, thrombocytopaenic purpura, agranulocytosis, pancytopaenia, eosinophilia, haemolytic anaemia, aplastic anaemia, bone marrow aplasia, eosinophilia and coagulation disorders have been reported with sulphonylureas. Potentially life threatening changes in the blood picture may occur. They may include, rarely, mild to severe thrombopaenia (e.g. presenting as purpura) and, in isolated cases, haemolytic anaemia, erythrocytopaenia, granulocytopaenia, agranulocytosis and (for example, due to myelosuppression) pancytopaenia. In principle, these reactions are reversible once glibenclamide has been withdrawn.

Hepatic reactions.

Increased liver enzymes (AST, ALT), abnormal liver function, cholestasis, cholestatic hepatitis, granulomatous hepatitis and bilirubinaemia have been reported with sulphonylureas. In isolated cases there may be hepatitis, elevation of liver enzyme levels and/or cholestasis and jaundice which may progress to life threatening liver failure but can regress after withdrawal of glibenclamide.

Miscellaneous.

Although a causal relationship has not been established, the following adverse effects have been reported in patients receiving glibenclamide: paresthesia, blindness, deafness, diplopia, visual disturbances, tremor, convulsions (other than withdrawal), encephalopathy, confusion, acute psychosis, abnormal renal function, acute renal failure, ocular disturbances (accommodation changes, crystalline lens changes), lactic acidosis, alopecia/hipotrichosis, hyponatraemia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), arthralgia, arthritis, cerebrovascular disorders, headache, facial oedema, angioedema, weight gain, hypersensitivity vasculitis and increased sweating.

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.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

Pathogenesis.

Acute glibenclamide toxicity may result from excessive dosage and numerous conditions may predispose patients to the development of glibenclamide induced hypoglycaemia (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use). Acute overdose as well as long-term treatment with too high a dose of glibenclamide may lead to severe, protracted, life threatening hypoglycaemia. Fatal hypoglycaemia has occurred with ingestion of as little as 2.5 to 5 mg of the drug.

Manifestations.

Acute glibenclamide overdosage is manifested principally as hypoglycaemia, which may be severe and has occasionally been fatal. Severe hypoglycaemia may result in loss of consciousness and seizures, with resultant neurologic sequelae.

Treatment.

In case of overdosage with glibenclamide, a doctor has to be called immediately. At the first signs of hypoglycaemia, the patient must immediately take sugar, preferably glucose, unless a doctor has already started care.
Since hypoglycaemia and its clinical symptoms may recur after apparent clinical recovery (even after several days), close and continued medical supervision and possibly referral to a hospital are indicated. In particular, significant overdosage and severe reactions, e.g. with unconsciousness or other neurological dysfunctions, are emergency cases and require immediate care and hospitalisation.
If hypoglycaemic coma is diagnosed or suspected, administration of glucagon (adults: 0.5-1 mg) i.v., s.c. or i.m., or i.v. infusion of a 20% glucose solution (adults: 40-100 mL) is indicated, until the patient recovers consciousness. In infants, glucose must be dosed very carefully, accompanied by close monitoring of blood glucose, taking into account the risk of potentially severe hyperglycaemia. Other symptomatic therapy (e.g. anticonvulsants) should be administered as necessary.
In cases of acute intake of large amounts of glibenclamide, detoxification, e.g. by medicinal charcoal as an absorbent, is indicated.
After acute glucose replacement has been completed, it is usually necessary to give an intravenous glucose infusion in lower concentration to ensure that the hypoglycaemia does not recur. The patient's blood glucose level should be carefully monitored for at least 24 hours. In severe cases with a protracted course, hypoglycaemia, or the danger of slipping back into hypoglycaemia, may persist for several days.

5 Pharmacological Properties

Oral hypoglycaemia.

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Drugs used in diabetes, Sulfonylureas, ATC code: A10BB01.

Mechanism of action.

Daonil appears to lower the blood glucose acutely in healthy individuals and patients with type 2 diabetes by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells. It acts in concert with glucose (improved sensitivity of beta cells to physiological glucose stimulus) and leads to an insulin secretion in the rhythm of meals. Other mechanisms of the hypoglycaemic action associated with short-term therapy appear to include reduction of basal hepatic glucose production and enhancement of peripheral insulin action at postreceptor (probably intracellular) sites.
With chronic administration of Daonil and Semi-Daonil in patients with type 2 diabetes, the improvement in glucose tolerance persists, despite a gradual decline in glucose or meal stimulated secretion of insulin towards pretreatment levels. Extrapancreatic effects appear to contribute substantially to the hypoglycaemic action of the drug during long-term administration. The effects appear to include enhanced peripheral sensitivity to insulin and reduction of basal hepatic glucose production. There is evidence that glibenclamide enhances the peripheral action of insulin at postreceptor (probably intracellular) sites and increases insulin binding and/or the number of insulin receptors.
Glibenclamide also exerts a direct inhibitory effect on glucagon producing alpha cells of the pancreas and increases the release of somatostatin. However, these two pancreatic extra-beta cell actions may play only a minor clinical role.
In addition to its blood glucose lowering effect, glibenclamide has a mild diuretic action and increases free water clearance.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Glibenclamide is nearly completely absorbed (84 + 9%) after oral administration and is extensively bound (99%) to serum proteins. The peak serum concentration is reached in 2-6 hours after taking a 5 mg tablet of Daonil and falls within 24 hours to less than 5% of the peak value. The area under the serum concentration time curve (AUC) increases in proportion to increasing doses. Food apparently does not affect the rate or extent of absorption of glibenclamide.

Distribution.

Multiple dose studies with glibenclamide in diabetic patients demonstrate drug level concentration time curves similar to single dose studies, indicating no buildup of drug in tissue depots. In nonfasting diabetic patients, the hypoglycaemic action of a single morning dose of glibenclamide persists for 24 hours.
Serum concentrations of glibenclamide appear to decline in a biphasic manner. The elimination half-life of glibenclamide after intravenous dosage is approximately 2 hours, and 2 to 5 hours after oral administration. Some reports indicate a longer half-life of 8 to 10 hours in patients with diabetes.

Metabolism.

Glibenclamide is completely metabolised in the liver. The drug is metabolised at the cyclohexyl ring principally to a 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites contribute some hypoglycaemic action; they are weakly active (0.25% and 2.5%, respectively, as glibenclamide) in rabbits.

Excretion.

Glibenclamide is excreted as metabolites in the bile and urine, approximately 50% by each route. In patients with renal insufficiency, depending on the degree of the renal excretion disorder, there is increased elimination of the metabolites via the bile. This dual excretory pathway is qualitatively different from that of other sulphonylureas, which are excreted primarily in the urine.
Glibenclamide appears to be only minimally removed by haemodialysis.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Daonil and Semi-Daonil*.

Lactose monohydrate, maize starch, pregelatinised maize starch (Daonil only), purified talc, colloidal anhydrous silica, magnesium stearate.
*Not marketed.

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

Daonil.

Store below 25°C. Protect from light.

Semi-Daonil*.

Store below 30°C. Protect from light.
*Not marketed.

6.5 Nature and Contents of Container

Daonil.

Blister packs of 10 (sample pack), 30, 60, 90 and 100 tablets.

Semi-Daonil*.

Blister packs of 10, 30, 60 and 90 tablets.
Not all pack sizes may be marketed.
*Not marketed.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Glibenclamide belongs to the sulphonylurea group of oral antidiabetics. Earlier members of this group are carbutamide, tolbutamide, acetohexamide and chlorpropamide. Chemically, it is 1-(4-(2-(5-chloro- 2-methoxybenzamido) ethyl) benzenesulfonyl)- 3-cyclohexylurea. It has a molecular weight of 494 and an empirical formula of C23H28ClN3O5S. It is a white, odourless, crystalline powder, practically insoluble in water and in ether, slightly soluble in alcohol and sparingly soluble in chloroform.

Chemical structure.


CAS number.

10238-21-8.

7 Medicine Schedule (Poisons Standard)

Prescription Medicine (Schedule 4).

Summary Table of Changes