Zicron 40mg Tablets

1. Name Of The Medicinal Product

Gliclazide 40mg Tablets

Zicron 40mg Tablets

2. Qualitative And Quantitative Composition

Gliclazide 40mg

For Excipients, see 6.1

3. Pharmaceutical Form

Tablet

White to off-white, circular, flat, bevelled edged, uncoated tablets with “40” on one side, plain on reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

Non insulin dependant diabetes mellitus.

4.2 Posology And Method Of Administration

For oral administration.

Adults:

The total daily dose may vary from 40 to 320 mg taken orally. The dose should be adjusted according to the individual patient's response, commencing with 40-80 mg daily (1 – 2 tablets) and increasing until adequate control is achieved. A single dose should not exceed 160 mg (4 tablets). When higher doses are required, gliclazide should be taken twice daily and according to the main meals of the day.

In obese patients or those not showing adequate response to gliclazide alone, additional therapy may be required.

Elderly:

Plasma clearance of gliclazide is not altered in the elderly and steady state plasma levels can therefore be expected to be similar to those in adults under 65 years. Clinical experience in the elderly to date shows that gliclazide is effective and well tolerated. Care should be exercised, however, when prescribing sulphonylureas in the elderly due to a possible age-related increased risk of hypoglycaemia.

Children:

Gliclazide as with other sulphonylureas, is not indicated for the treatment of juvenile onset diabetes mellitus.

4.3 Contraindications

Gliclazide should not be used in:

- Juvenile onset diabetes.

- Diabetes complicated by ketosis and acidosis.

- Pregnancy.

- Diabetes undergoing surgery, after severe trauma or during infections.

- Patients known to have hypersensitivity to other sulphonylureas and related drugs or any of the other tablet ingredients.

- Diabetic pre-coma and coma.

- Severe renal or hepatic insufficiency.

4.4 Special Warnings And Precautions For Use

- Hypoglycaemia: all sulphonylurea drugs are capable of producing moderate or severe hypoglycaemia, particularly in the following conditions:

- in patients controlled by diet alone,

- in cases of accidental overdose,

- When calorie or glucose intake is deficient,

- in patients with hepatic and/or renal impairment; however, in long-term clinical trials, patients with renal insufficiency have been treated satisfactorily, using gliclazide at reduced doses.

In order to reduce the risk of hypoglycaemia it is therefore recommended:

- to initiate treatment for non-insulin dependant diabetes by diet alone, if this is possible,

- to take into account the age of the patient: blood sugar levels not strictly controlled by diet alone might be acceptable in the elderly,

- to adjust the dose of gliclazide according to the blood glucose response and to the 24 hour urinary glucose during the first days of treatment.

Dosage adjustments may be necessary:

- on the occurrence of mild symptoms of hypoglycaemia (sweating, pallor, hunger pangs, tachycardia, sensation of malaise). Such findings should be treated with oral glucose and adjustments made in drug dosage and/or meal patterns,

- on the occurrence of severe hypoglycaemic reactions (coma or neurological impairment, see overdose),

- loss of control of blood glucose (hyperglycaemia). 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 increase progressively the dosage of gliclazide and it this is insufficient, to discontinue the treatment with gliclazide and to administer insulin. As with other sulphonylureas, hypoglycaemia will occur if the patient's dietary intake is reduced or of they are receiving a larger dose of gliclazide than required.

- Care should be exercised in patients with hepatic and/or renal impairment and a small starting dose should be used with careful patient monitoring.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Care should be taken when giving gliclazide with drugs which are known to alter the diabetic state or potentiate the drug's action.

The hypoglycaemic effect of gliclazide may be potentiated by phenylbutazone, salicylates, sulphonamides, coumarin derivatives, MAOIs, beta adrenergic blocking agents, tetracycline compounds, chloramphenicol, clofibrate, disopyramide, miconazole (oral forms) and cimetidine.

It may be diminished by corticosteroids, oral contraceptives, thiazide diuretics, Phenothiazine derivatives, thyroid hormones and abuse of laxatives.

4.6 Pregnancy And Lactation

Pregnancy:

Gliclazide is contraindicated during pregnancy (see section 4.3 contra-indications).

Lactation:

It has not been established whether gliclazide is transferred to human milk. However, other sulphonylureas have been found in milk and there is no evidence to suggest that gliclazide differs from the group in this respect. Gliclazide should, therefore, not be taken while the mother is breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

Patients should be informed that their concentration may be affected if their diabetes is not satisfactorily controlled, especially at the beginning of treatment (see special warnings and precautions).

4.8 Undesirable Effects

- Hypoglycaemia (see special warnings and precautions).

- Abnormalities of hepatic function are not uncommon during gliclazide therapy. There are rare reports of hepatic failure, hepatitis and jaundice following treatment with gliclazide.

- Mild gastro-intestinal disturbances including nausea, dyspepsia, diarrhoea, constipation have been reported but this type of adverse reaction can be avoided if gliclazide is taken during a meal.

- Skin reactions including rash, pruritus, Erythema, bullous eruption; blood dyscrasia including anaemia, leukopenia, thrombocytopenia and granulocytopenia have been observed during treatment with gliclazide but are not known to be directly attributable to the drug.

4.9 Overdose

The symptoms to be expected of overdose would be hypoglycaemia. The treatment is gastric lavage and correction of the hypoglycaemia by appropriate means with continual monitoring of the patient's blood sugar until the effect of the drug has ceased.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

A10B B09 Oral Blood Glucose Lowering Drugs

Gliclazide is a hypoglycaemic sulphonylurea differing from other related compounds by the addition of an azabicyclo-octane ring.

In man, apart from having similar hypoglycaemic effect to the other sulphonylureas, gliclazide has been shown to reduce platelet adhesiveness and aggregation and increase fibrinolytic activity. These factors are thought to be implicated in the pathogenesis of long-term complications of diabetes mellitus.

Gliclazide primarily enhances the first phase of insulin secretion, but also to a lesser degree its second phase. Both phases are diminished in non-insulin dependant diabetes mellitus.

5.2 Pharmacokinetic Properties

The drug is well absorbed and its half-life in man is approximately 10-12 hours. Gliclazide is metabolised in the liver; less than 5% of the dose is excreted unchanged in the urine.

5.3 Preclinical Safety Data

No data of relevance which is additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose monohydrate

Microcrystalline cellulose

Magnesium stearate

Purified talc

Croscarmellose sodium

Povidone

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

2 years

6.4 Special Precautions For Storage

Blisters:	Do not store above 25ºC. Store in the original package.
Tablet containers:	Do not store above 25ºC. Keep the container tightly closed.

6.5 Nature And Contents Of Container

Al/PVC/PVDC blister, pack sizes of 20, 28, 56, 60, 84, 100 tablets.

HDPE tablet containers, pack sizes of 100, 250, 500 or 1000 tablets.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Bristol Laboratories Limited

Unit 3, Canalside

Northbridge Road

Berkhamsted

Hertfordshire

HP4 1EG

8. Marketing Authorisation Number(S)

PL 17907/0067

9. Date Of First Authorisation/Renewal Of The Authorisation

12/06/2007

10. Date Of Revision Of The Text

July 2008