Betanase

Indications

• Type 2 diabetes mellitus
• Maturity-onset diabetes of the young (specialist use only)

Dosage

Children: For children aged 12-17 years, the initial dose is 2.5 mg daily, adjusted according to response, with a maximum dose of 15 mg per day.

Adults: Initially, 2.5 mg once daily, adjusted according to response, with a maximum dose of 15 mg per day. The dose should be taken with or immediately after breakfast.

Mechanism of action

Glibenclamide acts by closing ATP-sensitive potassium channels (SUR1) on pancreatic beta cells. Under low glucose concentrations, these channels remain open, allowing potassium efflux and maintaining a negative membrane potential. In the presence of glucose, SUR1 closes, leading to depolarization, opening of voltage-gated calcium channels, and subsequent insulin release. Glibenclamide bypasses the glucose-dependent mechanism, directly closing SUR1 and stimulating insulin secretion.

Pharmacodynamics

As a sulfonylurea, glibenclamide increases insulin secretion and raises intracellular potassium and calcium ion concentrations. It has a wide therapeutic index and is typically started at low doses, adjustable based on patient response. The drug is associated with an increased risk of cardiovascular mortality, similar to other sulfonylureas, necessitating careful monitoring of patients.

Pharmacokinetics

Glibenclamide is absorbed well from the gastrointestinal tract, with peak plasma concentrations occurring about 1-2 hours after oral administration. It undergoes hepatic metabolism, primarily by cytochrome P450 enzymes, and has an elimination half-life of approximately 5-10 hours. The drug is excreted mainly in urine and its pharmacokinetics can be affected by renal and hepatic function, necessitating dose adjustments in impaired patients.

Contra-indications

• Presence of ketoacidosis
• G6PD deficiency
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Common: Abdominal pain
• Common: Diarrhoea
• Common: Nausea
• Common: Vomiting
• Common: Altered taste
• Rare: Agranulocytosis
• Rare: Erythropenia
• Rare: Granulocytopenia
• Rare: Hemolytic anaemia
• Rare: Leucopenia
• Rare: Pancytopenia
• Rare: Thrombocytopenia
• Frequency not known: Allergic dermatitis
• Frequency not known: Constipation
• Frequency not known: Visual impairment

Interactions

• Bosentan: Severe (increases risk of hepatotoxicity)
• Roxadustat: Moderate (increases exposure)
• Darolutamide: Unknown (increases concentration)
• Bulevirtide: Unknown (increases exposure)
• Ceftobiprole: Unknown (increases concentration)
• Elexacaftor: Unknown (increases exposure)
• Leflunomide: Unknown (increases exposure)
• Letermovir: Unknown (increases concentration)
• Fluvastatin: Unknown (increases exposure)
• Taxanes: Unknown (affects exposure)

Precautions

• Can encourage weight gain
• Monitor renal function before treatment and at least annually
• Patients should be informed of the risk of lactic acidosis and symptoms to seek immediate medical attention
• Caution in patients with mild to moderate renal impairment
• Care required to use the lowest dose that adequately controls blood glucose
• Drivers should be warned of the risk of hypoglycaemia

Pregnancy

Can be used in pregnancy for both pre-existing and gestational diabetes; discontinue treatment after giving birth for gestational diabetes.

Breast-feeding

May be used during breastfeeding in women with pre-existing diabetes.

Storage

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

Formulations

• Tablets: 2.5 mg

Mechanism of action

Glyburide belongs to a class of drugs known as sulfonylureas. These drugs act by closing ATP-sensitive potassium channels on pancreatic beta cells. The ATP-sensitive potassium channels on beta cells are known as sulfonylurea receptor 1 (SUR1). Under low glucose concentrations, SUR1 remains open, allowing for potassium ion efflux to create a -70mV membrane potential. Normally SUR1 closes in response to high glucose concentrations, the membrane potential of the cells becomes less negative, the cell depolarizes, voltage gated calcium channels open, calcium ions enter the cell, and the increased intracellular calcium concentration stimulates the release of insulin containing granules. Glyburide bypasses this process by forcing SUR1 closed and stimulating increased insulin secretion.

Pharmacodynamics

Glyburide is a second generation sulfonylurea that stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations. Glibenclamide has a long duration of action as it is given once daily, and a wide therapeutic index as patients are started at doses as low as 0.75mg but that can increase as high as 10mg or more. Patients taking glyburide should be cautioned regarding an increased risk of cardiovascular mortality as seen with tolbutamide, another sulfonylurea.