PICAMAR 80

Indications

• Type 2 diabetes mellitus
• Adjunct to diet and exercise to improve glycemic control
• Monotherapy in patients intolerant to metformin

Dosage

Children: Child 12–17 years: Initially 20 mg once daily, adjusted according to response, increased if necessary up to 160 mg once daily (maximum 160 mg twice daily), taken with breakfast.

Adults: Initially 30 mg daily, taken with breakfast; adjust according to response every 4 weeks, maximum 120 mg per day. Doses higher than 160 mg should be given in divided doses.

Mechanism of action

Gliclazide binds to the beta cell sulfonylurea receptor (SUR1), blocking ATP-sensitive potassium channels. This leads to the closure of these channels, resulting in decreased potassium efflux and depolarization of the beta cells. The depolarization opens voltage-dependent calcium channels, which activate calmodulin, resulting in the exocytosis of insulin-containing secretory granules.

Pharmacodynamics

As a second-generation sulfonylurea, gliclazide acts as a hypoglycemic agent by stimulating insulin release from the beta cells of the islets of Langerhans in the pancreas. Additionally, it enhances peripheral insulin sensitivity, thereby improving insulin dynamics and overall glycemic control in patients with type 2 diabetes.

Pharmacokinetics

Gliclazide is well absorbed after oral administration, with peak plasma concentrations typically achieved within 4-6 hours. It is extensively metabolized in the liver, and its metabolites are primarily excreted via the urine. The elimination half-life is approximately 10-12 hours. Renal impairment may necessitate careful monitoring of blood glucose concentrations due to altered drug clearance.

Contra-indications

• Presence of diabetic ketoacidosis
• Acute porphyrias

Adverse effects

• Hypoglycaemia
• Nausea
• Dizziness
• Weight gain
• Gastrointestinal disorders
• Severe cutaneous adverse reactions (SCARs)
• Aplastic anaemia
• Angioedema
• Hyponatraemia
• Headache
• Photosensitivity reactions
• Fatigue
• Exfoliative dermatitis
• Fever
• Paraesthesia

Interactions

• Other blood glucose lowering drugs
• Alcohol (may cause alcohol intolerance)
• Certain medications that may affect blood glucose levels

Precautions

• Monitoring of blood glucose levels is essential, especially in patients at risk of hypoglycaemia
• Caution in elderly patients or those with renal impairment
• G6PD deficiency should be considered
• Weight gain may occur with long-term use

Pregnancy

The use of sulfonylureas in pregnancy should generally be avoided because of the risk of neonatal hypoglycaemia.

Breast-feeding

The use of sulfonylureas in breastfeeding should be avoided due to the theoretical possibility of hypoglycaemia in the infant.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Immediate-release tablets (e.g. 80 mg)
• Modified-release tablets (e.g. 30 mg, 120 mg)
• Oral suspension (available from special-order manufacturers)

Mechanism of action

Gliclazide binds to the β cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the β cells. This opens voltage-dependent calcium channels in the β cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules.

Pharmacodynamics

Based on the pharmacological properties, gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.