Gliclazide

Registered South African indications:

• Type 2 diabetes mellitus
  - Indicated in association with dietary measures, lifestyle changes, and exercise, when these alone are not sufficient to control blood glucose

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of the excipients
• Hypersensitivity to sulphonylureas or sulphonamides 
• Type 1 diabetes mellitus (Juvenile Insulin Dependent Diabetes Mellitus), diabetic ketoacidosis, diabetic pre-coma, and coma
• Significant acidosis, severe burns, severe infection, or hyperosmolar nonketotic coma
• Major surgery or severe trauma
• Severe renal or hepatic insufficiency, in these cases the use of insulin is recommended
• Treatment with miconazole
• Children
• Pregnancy
• Lactation

Contraindications registered in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Type 1 diabetes
• Diabetes complicated by ketosis and acidosis
• Diabetic pre-coma and coma
• Severe renal or hepatic insufficiency: in these cases the use of insulin is recommended
• Lactation
• Treatment with miconazole

• Pregnancy (Recommendations in other jurisdictions)
• Mild to moderate renal impairment (MR tab) (South African recommendations)
• Renal impairment (Immediate release tab) (South African recommendations)
• Mild to moderate renal impairment (Recommendations in other jurisdictions)
• Mild to moderate hepatic impairment
• Elderly
• Debilitated
• Malnourished
• Severe endocrine disorders
• Withdrawal from prolonged/high dose corticosteroids
• Severe vascular disease
• Low-calorie diet
• Food insecurity
• Periods of physiological stress
• Glucose-6-phosphate-deficiency
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab, srt, modified release tab (MR tab)

South African registered indications and dosages

Type 2 diabetes mellitus
- Indicated in association with dietary measures, lifestyle changes, and exercise, when these alone are not sufficient to control blood glucose

Modified-release tablet

• Oral (tab, MR tab, srt): Initial: 30mg, once daily; Maintenance: 30-120mg, taken as a single daily dose with breakfast; Dose adjustments: If fasting blood glucose levels are not satisfactorily decreased, dosage can be increased progressively to 60, 90, or 120mg per day, by successive increments, at least 1 month apart, except in patients whose blood glucose has not decreased after 15 days of treatment. In this case, dosage may be increased at the end of the 2nd week; Max: 120mg/24hrs

Previously untreated patients should commence with a dose of 30mg

Missed dose: If a dose is forgotten, do not increase the next day’s dose

Switching recommendations
From gliclazide 80mg to MR tablet: Replacement based on: 1 tablet of Gliclazide 80mg = 1 x 30mg MR tablet

From another sulphonylurea to MR tablet: Consider dosage and half-life of the previous medication. If switched from a sulphonylurea with a prolonged half-life, a treatment-free window may be necessary to avoid hypoglycemia. Start with 30mg per day and adjust dosage based on patient’s metabolic response

Combination Therapy: The MR tablet can be used with alpha-glucosidase inhibitors or insulin; monitor for hypoglycaemia. Use caution when combining with biguanides due to potential increased risk of cardiovascular mortality

Immediate-release tablet

• Oral (tab): Initial: 40-80mg, daily; Dose adjustments: If necessary, gradually increase up to 320mg, daily; Admin. for doses over 160mg daily: Given in 2 divided doses

Not established for use in children and adolescents

Pregnancy 

South African recommendations

• Contraindicated
• Safety in pregnancy has not been established

Recommendations in other jurisdictions

• Caution; not recommended
• As a precautionary measure, it is preferable to avoid the use of gliclazide during pregnancy
• 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

Breastfeeding

South African recommendations

• Contraindicated
• Safety in breastfeeding mothers has not been established

Recommendations in other jurisdictions

• Contraindicated
• It is unknown whether gliclazide or its metabolites is excreted in human milk. Given the risk of neonatal hypoglycaemia the product is contraindicated in breast-feeding mother. A risk to the newborns/infants cannot be excluded

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• No effect on fertility or reproductive performance was noted in male and female rats

South African recommendations

MR tablet

• Mild to moderate (30-80ml/min): Caution; no dose adjustment recommended
  A reduction in dosage may be necessary in patients with renal dysfunction. The dosage is identical to that recommended for patients with normal renal function, with careful monitoring
• Severe: Contraindicated

Immediate release tablet

• Caution; dose adjustment recommended
  Reduction in dose may be necessary in patients with renal dysfunction

Recommendations in other jurisdictions

• Mild to moderate: Caution; no dose adjustment recommended
   The same dosing regimen can be used as in patients with normal renal function with careful patient monitoring. These data have been confirmed in clinical trials
• Severe: Contraindicated

Recommendations below are applicable to South Africa and other jurisdictions

• Mild to moderate: Caution; no dose adjustment recommended
  The pharmacokinetics and/or pharmacodynamics of gliclazide may be altered in patients with hepatic insufficiency. A hypoglycaemic episode occurring in these patients may be prolonged; so appropriate management should be initiated
• Severe: Contraindicated
  In these cases the use of insulin is recommended

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended
  The dosage is identical to that recommended for adults under the age of 65 years, and for patients with normal renal function, with careful patient monitoring

Central Nervous System Disorders

• Headaches
• Lassitude
• Sleep disorders
• Agitation 
• Aggression
• Poor concentration
• Reduced awareness
• Slowed reactions
• Depression
• Confusion
• Aphasia
• Tremor
• Paresis
• Dizziness
• Delirium
• Convulsions
• Coma
• Speech disorders

Cardiovascular Disorders

• Tachycardia
• Hypertension
• Palpitations
• Angina pectoris
• Cardiac arrhythmia
• Bradycardia

Respiratory Disorders

• Shallow breathing

Gastrointestinal Disorders

• Abdominal pain 
• Dyspepsia 
• Diarrhoea
• Constipation

Hepatobiliary Disorders

• Raised hepatic enzyme levels 
• Hepatitis

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Intense hunger

Skin and Subcutaneous Tissue Disorders

• Rash
• Clammy skin
• Sweating
• Pruritus 
• Urticaria
• Angioedema
• Erythema
• Maculopapular rashes 
• Bullous reactions
• Drug Rash with Eosinophilia and Systemic Symptoms

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Leucopenia 
• Thrombocytopenia 
• Granulocytopenia

Sensory Disorders

• Transient visual disturbances

• Miconazole
• Phenylbutazone
• Alcohol
• Insulin
• Acarbose
• Metformin
• Thiazolidinediones
• Dipeptidyl peptidase-4 inhibitors
• GLP-1 receptors agonists
• Beta-blockers
• Fluconazole
• Angiotensin converting enzyme inhibitors
• Monoamine oxidase inhibitors
• Sulfonamides
• Clarithromycin
• Non-steroidal anti-inflammatory drugs
• Danazol
• Chlorpromazine
• Glucorticoids 
• Ritodrine
• Salbutamol
• Terbutaline
• Anticoagulant therapy

• Renal function
• Hepatic function

Gliclazide stimulates the release of insulin from functioning pancreatic beta cells and increases the sensitivity of peripheral tissues to insulin. On the pancreatic cell surface, gliclazide binds to ATP-sensitive potassium channel receptors reducing potassium conductance and causing depolarization of the membrane. This depolarization stimulates calcium ions to move intracellularly and the increased intracellular calcium ion concentration induces the secretion of insulin.

Slow release tablet 30mg

• Dyna Gliclazide SR 30mg (Pharma Dynamics)
• Glytab 30 (Forrester)

Tablet MR 30mg 

• Diamicron MR 30mg (Servier Laboratories) originator
• Diaran MR 30 (Ranbaxy)
• Diaglucide MR 30mg (Biogaran)
• Gliclazide MR 30 Austell (Austell Laboratories)
• Gliclazide Unicorn MR 30 (Biogaran)
• Gluctam MR 30mg (Servier Laboratories S.A)

Tablet MR 60mg 

• Diamicron MR 60mg (Servier Laboratories) originator
• Diagen MR 60 (Mylan)
• Diaglucide MR 60mg (Servier Laboratories)
• Dynacaz 60 mg MR ( Pharma Dynamics)
• Gliclazide MR 60 Austell (Austell Laboratories)

Tablet 40mg 

• Austell Gliclazide (Austell Laboratories)

Tablet 80mg

• Adco-Glucomed (Adcock Ingram)
• Arrow Gliclazide (Arrow Pharma)
• Austell Gliclazide 80mg (Austell Laboratories)
• Coninsul ( Trinity Pharma)
• Diaglucide (Servier Laboratories)
• Diaglumed 80 (Dezzo Trading)
• Diamicron (Servier Laboratories) originator
• Gliclazide Unicorn 80 (Servier)
• Glycobeta (Gulf Drug Company)
• Glycron (Pharmacare)
• Glygard (Cipla Medpro)
• Sandoz Gliclazide 80 (Sandoz)