Consumer medicine information

Minidiab

Glipizide

BRAND INFORMATION

Brand name

Minidiab

Active ingredient

Glipizide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Minidiab.

What is in this leaflet

This leaflet answers some common questions about Minidiab. It does not contain all the available information and 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 Minidiab 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 your medicine. You may need to read it again.

What Minidiab is used for

What Minidiab does

Minidiab is used in addition to diet and exercise to control blood sugar in patients with Type II diabetes mellitus. This type of diabetes is also known as non-insulin-dependent diabetes mellitus (NIDDM) or maturity onset diabetes.

Minidiab is used when diet and exercise are not enough to control blood sugar (glucose). Minidiab can be used alone, or together with insulin or other medicines for treating diabetes.

How Minidiab works

Minidiab belongs to a group of medicines called sulphonylureas. These medicines lower high blood glucose by increasing the amount of insulin produced by your pancreas.

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.

Hypoglycaemia (low blood glucose) can occur suddenly. Signs may include:

  • weakness, trembling or shaking
  • sweating
  • lightheadedness, dizziness, headache or lack of concentration
  • tearfulness or crying
  • irritability
  • hunger
  • numbness around the lips and tongue.

If not treated properly, these may progress to:

  • loss of co-ordination
  • slurred speech
  • confusion
  • loss of consciousness or fitting.

Hyperglycaemia (high blood glucose) usually occurs more slowly than low blood glucose.

Signs of high blood glucose may include:

  • lethargy or tiredness
  • headache
  • thirst
  • passing large amounts of urine
  • blurred vision.

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

This medicine is available only with a doctor's prescription.

There is no evidence that Minidiab is addictive.

Use in Children

Minidiab is not recommended for use in children.

Before you take Minidiab

When you must not take it

Do not take Minidiab if you have an allergy to:

  • any medicines containing glipizide
  • any of the ingredients listed at the end of this leaflet
  • other sulphonylureas
  • sulfur antibiotics (e.g. sulphonamides) or thiazide diuretics (e.g. chlorothiazide).

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 Minidiab if you have or have had any of the following conditions:

  • Type I diabetes mellitus (insulin dependent diabetes mellitus)
  • diabetes ketoacidosis with or without coma
  • severe kidney disease
  • severe liver disease
  • severe thyroid disease
  • severe or unstable diabetes
  • infection or high temperature
  • gangrene
  • severe trauma
  • major surgery.

If you are not sure about any of the above, ask your doctor.

Do not take Minidiab if you are pregnant or intend to become pregnant. Insulin is more suitable for controlling blood glucose during pregnancy. Your doctor may replace Minidiab with insulin.

Do not take Minidiab if you are breast-feeding or plan to breast-feed. It is not known whether Minidiab passes into breast-milk. There could be a possibility that your baby may be affected.

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 if you should start taking Minidiab, talk to your doctor.

Before you start to take it

Tell your doctor if you are allergic to any other medicines or any other substances such as foods, preservatives or dyes.

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

  • kidney problems
  • liver problems
  • adrenal or pituitary or thyroid problems
  • haemolytic anaemia or G6PD deficiency (a condition where the body does not have enough of the enzyme glucose-6-phosphate dehydrogenase).

Tell your doctor if:

  • you ever drink alcohol
  • you do not eat regular meals
  • you do a lot of heavy exercise
  • you are feeling ill or unwell.

Alcohol, diet and exercise 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.

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

Taking other medicines

Tell your doctor, pharmacist or diabetes educator if you are taking any other medicines, including:

  • all prescription medicines
  • all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines and Minidiab may interfere with each other.

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

These include:

  • alcohol
  • some medicines used to treat high blood pressure or other heart conditions (beta-blockers, ACE inhibitors, diazoxide)
  • some medicines used to treat arthritis, pain and inflammation (salicylates e.g. aspirin; non-steroidal anti-inflammatory drugs)
  • some antibiotics (e.g. chloramphenicol, sulphonamides and others)
    Tell your doctor or pharmacist if you are on antibiotic treatment.
  • some medicines used to treat fungal infections (miconazole, fluconazole)
  • medicines used to prevent blood clots (coumarin derivatives)
  • some cholesterol-lowering medicines (clofibrate)
  • other medicines used to treat diabetes (biguanides)
  • probenecid (a medicine used to treat gout or to increase the blood levels of some antibiotics)
  • some medicines used to treat depression (monoamine oxidase inhibitors)
  • some medicines used to treat reflux and ulcers (H2 receptor antagonists e.g. cimetidine)
  • some medicines used to treat cancer (cyclophosphamide).

Some medicines may lead to a loss of control of your diabetes by lowering the effect of Minidiab on blood glucose.

These include:

  • some medicines used to treat high blood pressure (calcium channel blocking medicines)
  • glucagon, a medicine used to treat low blood glucose
  • corticosteroids such as prednisone and cortisone
  • some medicines used to treat tuberculosis (isoniazid)
  • nicotinic acid (used for the lowering of blood fats)
  • oestrogens, progestogens, oral contraceptives and certain other hormonal treatments such as danazol.

These medicines are used for example in birth control, Hormone Replacement Therapy (HRT), or to treat other women's health problems.

  • some medicines used to treat mental illness or psychotic disorders (phenothiazines)
  • phenytoin, a medicine used to treat epilepsy (convulsions)
  • diuretics, also known as fluid tablets (thiazides)
  • some asthma medicines, preparations for coughs and colds, and weight-reducing medicines
  • thyroid hormones
  • some medicines used to treat cancer (cyclophosphamide).

Minidiab may change the effect of some other medicines. These include:

  • barbiturates (used for sedation).

You may need different amounts of your medicine or you may need to take different medicines.

Tetracycline, a type of antibiotic, can interfere with the measurement of glucose in the urine.

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 Minidiab.

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

How to take Minidiab

Follow all directions given to you by your doctor, pharmacist or diabetes educator carefully. These 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.

How much to take

The dose varies from patient to patient.

Your doctor will recommend how many tablets to take each day.

The usual starting dose is 1 tablet taken before breakfast. However, a lower starting dose may be needed in older people or those with liver problems.

Your doctor may increase or decrease the dose depending on your blood glucose levels.

How to take it

Swallow your tablets with a glass of water.

When to take it

For best control of blood sugar, Minidiab should be taken about half an hour before meals. Your doctor may recommend that you take your tablet(s) just once a day or may divide the dose so that it is taken more than once a day.

Do not skip meals while taking Minidiab.

How long to take it

Continue taking Minidiab for as long as your doctor recommends. Make sure you keep enough Minidiab to last over weekends and holidays. Minidiab will help to 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 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, then go back to taking your tablets as you would do normally.

Missed doses can cause hyperglycaemia.

Do not take a double dose to make up for the dose you have missed.

If you miss more than one dose or are not sure what to do, check with your doctor or pharmacist.

If you take too much (overdose)

If you think that you or anyone else may have taken too much Minidiab, immediately telephone your doctor or Poisons Information Centre for advice - the telephone number is 13 11 26 Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep telephone numbers for these places handy.

If you take too much Minidiab, you may experience symptoms of hypoglycaemia.

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

If not treated quickly, these symptoms may progress to loss of co-ordination, slurred speech, loss of consciousness and fitting. If you experience any of these symptoms, immediately get medical help.

While you are taking Minidiab

Things you must do

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

If you are about to start taking any new medicines, tell your doctor or pharmacist that you are taking Minidiab.

Tell all doctors, dentists and pharmacists who are treating you that you are taking Minidiab.

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

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

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 Minidiab
  • taking certain other medicines
  • too little exercise
  • eating more carbohydrate than normal.

If you become ill, or experience extra stress, injury, fever, infection or need surgery, tell your doctor. Your blood glucose may be difficult to control at these times. Your doctor may decide to change your treatment and use insulin instead of Minidiab.

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 regularly so that they can check on your progress.

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

Tell your doctor immediately if you notice the return of any symptoms you had before starting Minidiab. These may include lethargy or tiredness, headache, thirst, passing of large amounts of urine and blurred vision. These may be signs that Minidiab is no longer working, even though you may have been taking it successfully for some time.

Things you must not do

Do not stop taking Minidiab or change the dose without first checking with your doctor.

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

Do not skip meals while taking Minidiab.

Things to be careful of

Protect your skin when you are in the sun, especially between 10am and 3pm. Minidiab may cause your skin to be more sensitive to sunlight than it is normally.

If outdoors, wear protective clothing and use a minimum of SPF 30+ sunscreen. If your skin does appear to be burning, tell your doctor immediately. Exposure to sunlight may cause a skin rash, itching, redness or severe sunburn.

Make sure you know how you react to Minidiab before you drive a car or operate machinery. Be careful not to let your blood glucose levels fall too low. Minidiab 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.

Drinking alcohol while taking Minidiab may make you feel sick. You may also have a headache, stomach pains, flushing, breathing difficulties or rapid heartbeat.

Things that would be helpful for your condition

Some self-help measures suggested below may help your condition. Your doctor or pharmacist can give you more information about these measures.

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 e.g. jelly beans, sugar sachets
  • carry emergency food rations in case of delay e.g. dried fruit, biscuits
  • keep Minidiab readily available.

If you become sick with a cold, fever or flu, it is very important to continue taking Minidiab, even if you feel 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

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

Minidiab helps most people with diabetes but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

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

Tell your doctor if...

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

  • signs of low blood glucose (hypoglycaemia) which may include weakness, trembling or shaking, sweating, light-headedness, headache, dizziness, sleepiness, irritability, tearfulness or crying, hunger and lack of concentration
  • confusion, shaking and feeling generally unwell. These may be experienced but are usually mild and transient. However, they may also be symptoms of hypoglycaemia
  • stomach upset including nausea (feeling sick), vomiting and stomach cramps or pain
  • diarrhoea or constipation
  • rashes, sores, redness, itching, or eczema.

Sometimes these effects may disappear following continued treatment but you should ask your doctor for advice if you experience skin problems while taking Minidiab.

  • visual disturbances which may include blurred vision, double vision and abnormal vision

These may be experienced but are usually mild and transient. However, they may also be symptoms of hypoglycaemia.

  • symptoms of sunburn such as redness, itching and blistering which may occur more quickly than normal.

Tell your doctor as soon as possible if...

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

  • yellowing of the skin or eyes (also called jaundice)
  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers.

Go to hospital if...

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital, if you notice any of the following:

  • signs of anaemia such as tiredness, being short of breath, looking pale and having seizures (or fits)
  • signs of liver disease such as nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin or eyes, and dark coloured urine.

The above list includes serious side effects. You may need urgent medical attention or hospitalisation. This is not a complete list of all possible side effects. Some people may get other side effects while taking Minidiab.

Tell your doctor if you notice anything else that is making you feel unwell while you are taking Minidiab.

After taking Minidiab

Storage

Keep your 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.

Keep your tablets in the blister pack until it is time to take them. The blister packaging will help protect the tablets.

Keep the pack in a cool, dry place where it stays below 30 °C.

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

Disposal

If your doctor tells you to stop taking Minidiab, or the tablets have passed their expiry date, ask your pharmacist what to do with any tablets left over.

Product description

What it looks like

Minidiab tablets are white, round, biconvex and scored so that they can be broken in half. Each pack contains 100 tablets in blister strips.

Ingredients

The active ingredient in Minidiab is glipizide. Each Minidiab tablet contains 5 milligrams of glipizide.

Each tablet also contains: cellulose, maize starch, stearic acid and lactose monohydrate.

Supplier

Minidiab tablets are supplied in Australia by:

Pfizer Australia Pty Ltd
Level 17, 151 Clarence Street
Sydney NSW 2000
Toll Free Number: 1800 675 229
www.pfizer.com.au

Australian registration number

AUST R 15421

Date of preparation

This leaflet was revised in October 2019.

© Pfizer Australia Pty Ltd

® Registered Trademark

Published by MIMS January 2020

BRAND INFORMATION

Brand name

Minidiab

Active ingredient

Glipizide

Schedule

S4

 

1 Name of Medicine

Glipizide.

6.7 Physicochemical Properties

Glipizide is a whitish, odourless powder with a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide.
Minidiab (glipizide) is an oral blood glucose lowering drug of the sulphonylurea class. The chemical name of glipizide is 1-cyclohexyl-3- [4[2-(5-methylpyrazine- 2-carboxamido)ethyl] -benzene-sulphonyl] urea. The molecular formula is C21H27N5O4S, molecular weight is 445.5.

Chemical structure.

The structural formula is shown below.

CAS number.

29094-61-9.

2 Qualitative and Quantitative Composition

Each tablet contains 5 mg of glipizide.

Excipient(s) with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

White, round, biconvex, scored tablets.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Minidiab is a sulphonylurea hypoglycaemic agent. The primary mode of action of Minidiab in experimental animals appears to be the stimulation of insulin secretion from the beta-cells of pancreatic islet tissue, and is thus dependent on functioning beta-cells in the pancreatic islets. In humans, Minidiab appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta-cells in the pancreatic islets. The mechanism by which Minidiab lowers blood glucose during long-term administration has not been clearly established. In man, stimulation of insulin secretion by Minidiab in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term Minidiab administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. The insulinotropic response to a meal occurs within 30 minutes after an oral dose of Minidiab in diabetic patients, but elevated insulin levels do not persist beyond the time of the meal challenge. Extrapancreatic effects may play a part in the mechanism of action of oral sulphonylurea hypoglycaemic drugs. Some patients fail to respond initially, or gradually lose their responsiveness to sulphonylureas, including Minidiab. Alternatively, Minidiab may be effective in some patients who have not responded, or have ceased to respond, to other sulphonylureas.

Duration of action.

Clinical studies show that blood sugar control persists in some patients for up to 24 hours after a single dose of Minidiab, even though plasma levels have declined to a small fraction of peak levels by that time.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Gastrointestinal absorption of Minidiab in humans is uniform, rapid and essentially complete. Peak plasma concentrations occur 1-3 hours after a single oral dose. The half-life of elimination ranges from 2-4 hours in normal subjects, whether given intravenously or orally. Total absorption and disposition of an oral dose were unaffected by food in normal volunteers, but absorption was delayed by about 40 minutes. Thus Minidiab was more effective when administered about 30 minutes before, rather than with, a test meal in diabetic patients.

Distribution.

Protein binding was studied in serum from volunteers who received either oral or intravenous Minidiab and found to be 92-99% one hour after either route of administration. The apparent volume of distribution of Minidiab after intravenous administration was 5-11 litres, indicative of localisation within the extracellular fluid compartment. In mice, neither Minidiab nor metabolites were detectable autoradiographically in the brain or spinal cord of males or females, nor in the fetuses of pregnant females. In another study, however, very small amounts of radioactivity were detected in the fetuses of rats given the labelled drug.

Metabolism and excretion.

The metabolism of Minidiab is extensive and occurs mainly in the liver. The primary metabolites are inactive hydroxylation products and polar conjugates, and are excreted mainly in the urine. Less than 3.0-4.3% unchanged Minidiab is found in the urine. The metabolic and excretory patterns are similar with both oral and IV routes of administration, indicating that first-pass metabolism is not significant. Minidiab does not accumulate in plasma on repeated oral administration.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Minidiab is indicated as an adjunct to diet and exercise for the control of hyperglycaemia and its associated symptomatology in patients with noninsulin dependent diabetes mellitus (NIDDM; type II), formerly known as maturity onset diabetes, after an adequate trial of dietary therapy has proved unsatisfactory. 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 program fails to reduce symptoms and/or blood glucose, the use of an oral sulphonylurea or insulin should be considered. Use of Minidiab 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. Furthermore, loss of blood glucose control on diet alone also may be transient, thus requiring only short-term administration of Minidiab. During maintenance programs, Minidiab should be discontinued if satisfactory lowering of blood glucose is no longer achieved. Judgments should be based on regular clinical and laboratory evaluations.

4.3 Contraindications

Minidiab is contraindicated in patients with:
Known hypersensitivity to glipizide or to other sulphonylurea derivatives;
Allergy to sulphonamides;
Diabetic ketoacidosis, with or without coma. This condition should be treated with insulin;
Juvenile, growth onset or brittle diabetes mellitus;
Severe renal or hepatic insufficiency;
Severe thyroid dysfunction;
Pregnancy;
Severe or unstable diabetes;
Infections and febrile conditions;
Gangrene;
Severe trauma;
Major surgical procedures.
Minidiab is also contraindicated in children.

4.4 Special Warnings and Precautions for Use

General.

The risks of hypoglycaemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure should also be explained. Patients should be informed of the potential risks and advantages of Minidiab and of alternative modes of therapy. They should also be informed about the importance of adhering to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

Since glipizide belongs to the class of sulfonylurea agents, caution should be used in patients with G-6-PD deficiency. Treatment of patients with G-6-PD deficiency with sulfonylurea agents can lead to haemolytic anaemia and a nonsulfonylurea alternative should be considered.

Hypoglycaemia.

All sulphonylurea agents are capable of producing severe hypoglycaemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycaemic episodes. Renal or hepatic insufficiency may cause elevated blood levels of Minidiab and may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycaemic reactions. Elderly, debilitated or malnourished patients and those with adrenal or pituitary insufficiency are particularly susceptible to the hypoglycaemic action of glucose lowering drugs. Hypoglycaemia may be difficult to recognise in the elderly and in people who are taking beta-adrenergic blocking drugs. Hypoglycaemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, alcohol is ingested, or when more than one glucose lowering drug is used.

Loss of control of blood glucose.

When a patient stabilised on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to discontinue Minidiab and administer insulin.

Secondary failure.

The effectiveness of any oral hypoglycaemic drug, including Minidiab, in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of the diabetes or due to diminished responsiveness to the drug. The phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when first given.

Use in hepatic and renal impairment.

The metabolism and excretion of Minidiab may be slowed in patients with impaired renal and/or hepatic function. If hypoglycaemia should occur in such patients, it may be prolonged and appropriate management should be instituted.

Use in the elderly.

In elderly patients, the initial and maintenance dosing should be conservative to avoid hypoglycaemic reactions.
See Section 4.4 Special Warnings and Precautions for Use, Hypoglycaemia; Section 4.2 Dose and Method of Administration.

Paediatric use.

Not for use in children (see Section 4.3 Contraindications).

Effects on laboratory tests.

Blood and urine glucose should be monitored periodically. Measurement of glycosylated haemoglobin and/or fructosamine levels may be useful.
The pattern of laboratory test abnormalities observed with Minidiab was similar to that for other sulphonylureas. Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase, BUN and creatinine were noted. One case of jaundice was reported. The relationship of these abnormalities to Minidiab is uncertain, and they have rarely been associated with clinical symptoms.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The hypoglycaemic action of sulphonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, quinolone antibiotics and drugs that are highly protein bound, salicylates, sulphonamides, clofibrate, biguanides, diazoxide, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta-adrenergic blocking agents.

Fluconazole.

There have been reports of hypoglycaemia following the coadministration of glipizide and fluconazole, possibly the result of an increased half-life of glipizide.

Alcohol.

Alcohol may increase the hypoglycaemic effect of Minidiab, which could lead to hypoglycaemic coma.

Angiotensin converting enzyme inhibitors.

The use of angiotensin converting enzyme inhibitors may lead to an increased hypoglycaemic effect in diabetic patients treated with sulphonylureas, including Minidiab. Therefore, a reduction in Minidiab dosage may be required.

H2-receptor antagonists.

The use of H2-receptor antagonists (i.e. cimetidine) may potentiate the hypoglycaemic effects of sulphonylureas, including Minidiab.

Voriconazole.

Although not studied, voriconazole may increase plasma level of sulfonylureas (e.g. tolbutamide, glipizide and glyburide) and therefore cause hypoglycaemia. Careful monitoring of blood glucose is recommended during coadministration.
When such drugs are administered to a patient receiving Minidiab, the patient should be observed closely for hypoglycaemia. When such drugs are withdrawn from a patient receiving Minidiab, the patient should be observed closely for loss of control. In vitro binding studies with human serum proteins indicated that Minidiab binds differently than tolbutamide and does not interact with salicylate or dicoumarol. However, caution must be exercised in extrapolating these findings to the clinical situation and in the use of Minidiab with these drugs.
Certain drugs tend to produce hyperglycaemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, oestrogens, progestogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, alcohol (chronic abuse), glucagon, and isoniazid. When such drugs are administered to a patient receiving Minidiab, the patient should be closely observed for loss of control. When such drugs are administered to (or withdrawn from) a patient receiving Minidiab, the patient should be observed closely for hypoglycaemia.
A potential interaction between oral miconazole and oral hypoglycaemic agents leading to severe hypoglycaemia has been reported. Whether this interaction also occurs with the intravenous, topical or vaginal preparations of miconazole is not known.
The risk of increase of effect of barbiturates is extremely low for pharmacokinetic reasons (nonionic protein binding).
Tetracycline may interfere with determination of urine glucose. Cyclophosphamide and derivatives should also be used with care in diabetic patients since increased and decreased effects of sulphonylureas have been reported.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Minidiab (glipizide) was found to be mildly fetotoxic in rat reproductive studies at all dose levels (5-50 mg/kg). The fetotoxicity has been similarly noted with other sulphonylureas, such as tolbutamide and tolazamide. The effect is perinatal and believed to be directly related to the pharmacologic (hypoglycaemic) action of Minidiab. In studies in rats and rabbits, no teratogenic effects were found. There are no adequate and well controlled studies in pregnant women.
Sulphonylureas are not suitable for the treatment of diabetes mellitus during pregnancy as significant metabolic changes occur during this period which make control difficult.
Although it is not known whether Minidiab is excreted in human milk, some sulphonylurea drugs are known to be excreted in human milk. Because the potential for hypoglycaemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If the drug is discontinued and diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

4.8 Adverse Effects (Undesirable Effects)

In controlled studies, the frequency of serious adverse reactions reported was low. Of 702 patients, 11.8% reported adverse reactions, and in only 1.5% was Minidiab discontinued.

Hypoglycaemia.

See Section 4.4 Special Warnings and Precautions for Use; Section 4.9 Overdose.

Gastrointestinal.

Gastrointestinal disturbances are the most common reactions. Gastrointestinal complaints were reported with the following approximate incidence: nausea and diarrhoea, (1.4%); constipation and gastralgia, (1%); vomiting (> 1%). They appear to be dose related and may disappear on division or reduction of dosage. Abdominal pain has also been reported. Cholestatic jaundice may occur rarely with sulphonylureas; Minidiab should be discontinued if this occurs.

Dermatologic.

Allergic skin reactions including rash, erythema, morbilliform or maculopapular eruptions, urticaria, pruritus, and eczema have been reported in about one in seventy patients. These may be transient and may disappear despite continued use of Minidiab; if skin reactions persist, the drug should be discontinued. Porphyria cutanea tarda and photosensitivity reactions have been reported with sulphonylureas.

Metabolic.

Hepatic porphyria and disulfiram-like reactions have been reported with sulphonylureas. In the mouse, Minidiab pretreatment did not cause an accumulation of acetaldehyde after ethanol administration. Clinical experience to date has shown that Minidiab has an extremely low incidence of disulfiram-like alcohol reactions.

Haematologic.

Leucopenia, agranulocytosis, thrombocytopenia, aplastic anaemia, haemolytic anaemia, and pancytopenia have been reported with sulphonylureas.

Endocrine reaction.

Cases of hyponatraemia, and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported with this and other sulphonylureas.

Miscellaneous.

Dizziness, drowsiness, vertigo and headache have each been reported in about one in fifty patients treated with Minidiab. Confusion, tremor and malaise have also been reported. They are usually transient and seldom require discontinuance of therapy. These symptoms together with weakness, clouding of vision etc. may be signs of hypoglycaemia. However, the risk of severe or prolonged hypoglycaemia is low.

Eye disorders.

Visual disturbances such as blurred vision, diplopia, and abnormal vision including visual impairment and decreased vision, have each been reported in patients treated with Minidiab. They are usually transient and do not require discontinuance of therapy. However, they may also be symptoms of hypoglycaemia.

Hepatobiliary disorders.

Impaired hepatic function and hepatitis have been reported.

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.

4.2 Dose and Method of Administration

Dosage.

Generally speaking, the drug should be taken about 30 minutes before meals in order to achieve the greatest reduction in postprandial hyperglycaemia. There is no fixed dosage regimen for the management of diabetes mellitus with Minidiab or any other hypoglycaemic agent. In addition to the usual monitoring of urinary glucose, the patient's blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e. inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e. loss of an adequate blood glucose lowering response after an initial period of effectiveness. Monitoring of glycosylated haemoglobin levels may also be of value.

Initial dose.

The recommended starting dose is 5 mg given before breakfast. Geriatric patients or those with liver disease may be started on 2.5 mg.

Dosage titration.

Dosage adjustments should ordinarily be in increments of 2.5 mg-5 mg, as determined by blood glucose response. At least several days should elapse between titration steps. If response to a single dose is not satisfactory, dividing that dose may prove effective. The maximum recommended once daily dose is 15 mg. Doses above 15 mg should ordinarily be divided and given before meals of adequate caloric content. The maximum recommended total daily dose is 40 mg.

Maintenance.

Some patients may be effectively controlled on a once-a-day regimen, while others show better response with divided dosing. Total daily doses above 15 mg should ordinarily be divided. Total daily doses above 30 mg have been safely given on a twice daily basis to long-term patients. In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycaemic reactions (see Section 4.4 Special Warnings and Precautions for Use).

Patients receiving insulin agents.

As with other sulphonylurea class hypoglycaemics, many stable noninsulin dependent diabetic patients receiving insulin may be safely placed on Minidiab.

Patients receiving other oral hypoglycaemic agents.

As with other sulphonylurea class hypoglycaemics, no transition period is necessary when transferring patients to Minidiab. Patients should be observed carefully (1-2 weeks) for hypoglycaemia when being transferred from longer half-life sulphonylureas (e.g. chlorpropamide) to Minidiab due to potential overlapping of drug effect.

4.7 Effects on Ability to Drive and Use Machines

The treatment of diabetes with Minidiab requires regular check-ups. Until optimum stabilisation has been achieved, for example during the changeover from other medications or during irregular use, the ability to drive and use machines may be impaired.

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).
There is no well documented experience with Minidiab overdosage. Overdosage of sulphonylureas including Minidiab can produce hypoglycaemia. Mild hypoglycaemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycaemic reactions with coma, seizure or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalisation.
If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 5.55 mmol/L. Patients should be closely monitored for a minimum of 24 to 48 hours since hypoglycaemia may recur after apparent clinical recovery.
Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal may reduce absorption of the medicine if given within one hour after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected. Clearance of Minidiab from plasma would be prolonged in people with liver disease. Because of the extensive protein binding of Minidiab, dialysis is unlikely to be of benefit.

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Cellulose, maize starch, stearic acid, lactose monohydrate.

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

The tablets are blister packed and available in pack size of 100 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes