Gliclazide

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with MAOIs.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with sulfonamides.

Glucocorticoids (systemic and local route:* intra-articular, cutaneous and rectal preparations) and tetracosactrin increase in blood glucose levels with possible ketosis (reduced tolerance to carbohydrates due to glucocorticoids).

Warn the patient and emphasise the importance of blood glucose monitoring, particularly at the start of treatment. It may be necessary to adjust the dose of the antidiabetic active substance during and after treatment with glucocorticoids.

Alcohol increases the hypoglycaemic reaction (by inhibiting compensatory reactions) that can lead to the onset of hypoglycaemic coma. Avoid alcohol or medicines containing alcohol.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with H₂-receptor antagonists.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with insulins.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with thiazolidinediones.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with dipeptidyl peptidase-4 inhibitors.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with GLP-1 receptor agonists.

Sulfonylureas may lead to potentiation of anticoagulation during concurrent treatment. Adjustment of the anticoagulant may be necessary.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with beta-blockers.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with angiotensin converting enzyme inhibitors.

In the event of concomitant use of gliclazide with fluoroquinolone, the patient should be warned of the risk of dysglycaemia and the importance of monitoring blood glucose should be emphasized.

Exposure to gliclazide is reduced by St. John’s wort (Hypericum perforatum).

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with nonsteroidal anti-inflammatory agents.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with acarbose.

Chlorpromazine (neuroleptic agent) in high doses (>100 mg per day of chlorpromazine) increases blood glucose levels (reduced insulin release).

Warn the patient and emphasise the importance of blood glucose monitoring. It may be necessary to adjust the dose of the antidiabetic active substance during and after treatment with the neuroleptic agent.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with clarithromycin.

Co-administration of gliclazide and danazole may cause an increase in blood glucose levels (diabetogenic effect of danazol).

If the use of this active substance cannot be avoided, warn the patient and emphasise the importance of urine and blood glucose monitoring. It may be necessary to adjust the dose of the antidiabetic agent during and after treatment with danazol.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with fluconazole.

Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when gliclazide is co-administered with metformin.

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

Ritodrine may increase glycemia due to the action of β₂-agonists. Emphasise the importance of monitoring blood glucose levels. If necessary, switch to insulin.

Salbutamol may increase glycemia due to the action of β₂-agonists. Emphasise the importance of monitoring blood glucose levels. If necessary, switch to insulin.

Terbutaline may increase glycemia due to the action of β₂-agonists. Emphasise the importance of monitoring blood glucose levels. If necessary, switch to insulin.

For gliclazide, no clinical data on exposed pregnancies are available, even though there are few data with other sulfonylureas.

Studies in animals have shown reproductive toxicity.

Control of diabetes should be obtained before the time of conception to reduce the risk of congenital abnormalities linked to uncontrolled diabetes.

Oral hypoglycaemic agents are not suitable, insulin is the drug of first choice for treatment of diabetes during pregnancy. It is recommended that oral hypoglycaemic therapy is changed to insulin before a pregnancy is attempted, or as soon as pregnancy is discovered.

It is not known whether gliclazide or its metabolites are excreted in breast milk. Given the risk of neonatal hypoglycaemia, the product is contra-indicated in breast-feeding mothers.

Gliclazide has no known influence on the ability to drive and use machines. However, patients should be informed that their concentration may be affected if their diabetes is not satisfactorily controlled, especially at the beginning of treatment.

Based on the experience with gliclazide, the following undesirable effects have to be mentioned.

Hypoglycaemia

As for other sulfonylureas, treatment with gliclazide can cause hypoglycaemia, if mealtimes are irregular and, in particular, if meals are skipped. Possible symptoms of hypoglycaemia are: headache, intense hunger, nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor concentration, reduced awareness and slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of powerlessness, loss of self-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness, possibly resulting in coma and lethal outcome.

In addition, signs of adrenergic counter-regulation may be observed: sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac arrhythmia.

Usually, symptoms disappear after intake of carbohydrates (sugar). However, artificial sweeteners have no effect. Experience with other sulfonylureas shows that hypoglycaemia can recur even when measures prove effective initially.

If a hypoglycaemic episode is severe or prolonged, and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalisation are required.

Gastrointestinal disturbances, including abdominal pain, nausea, vomiting, dyspepsia, diarrhoea and constipation have been reported: if these should occur they can be avoided or minimised if gliclazide is taken with breakfast.

The following undesirable effects have been more rarely reported

Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson syndrome and toxic epidermal necrolysis).

Blood and lymphatic system disorders: Changes in haematology are rare. They may include anaemia, leucopenia, thrombocytopenia, granulocytopenia. These are in general reversible upon discontinuation of gliclazide.

Hepatobiliary disorders: Raised hepatic enzyme levels (ASAT, ALAT, alkaline phosphatase), hepatitis (isolated reports). Discontinue treatment if cholestatic jaundice appears.

These symptoms usually disappear after discontinuation of treatment.

Eye disorders: Transient visual disturbances may occur, especially on initiation of treatment, due to changes in blood glucose levels.

Class attribution effects

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