Diazoxide tablets are used orally in the treatment of intractable hypoglycaemia.

Hypoglycaemia: Diazoxide is indicated for the treatment of intractable hypoglycaemia with severe symptoms from various causes, including idiopathic hypoglycaemia in infancy, leucine-sensitive or unclassified hypoglycaemia, functional islet cell tumours (both benign and malignant) when inoperable, extra-pancreatic tumours producing hypoglycaemia, glycogen storage disease, and hypoglycaemia of unknown origin. Diazoxide may also cause salt and water retention.

Diazoxide is a benzothiadiazine derivative, specifically the S,S-dioxide of 2H-1,2,4-benzothiadiazine, substituted at position 3 by a methyl group and at position 7 by chlorine. It is a peripheral vasodilator that increases plasma glucose concentration and inhibits insulin secretion from pancreatic beta cells. It is used orally in the management of intractable hypoglycaemia and intravenously in hypertensive emergencies. It has multiple pharmacological roles including antihypertensive agent, sodium channel blocker, vasodilator, K-ATP channel agonist, beta-adrenergic agonist, cardiotonic drug, bronchodilator, sympathomimetic agent, and diuretic. It is classified as a benzothiadiazine, sulfone, and organochlorine compound.

As a diuretic, Diazoxide inhibits active chloride reabsorption in the early distal tubule via the Na-Cl cotransporter, leading to increased excretion of sodium, chloride, and water. Thiazide-like drugs such as Diazoxide also inhibit sodium transport across the renal tubular epithelium by binding to the thiazide-sensitive sodium-chloride transporter, resulting in increased potassium excretion through the sodium-potassium exchange mechanism. The antihypertensive effect of Diazoxide is not fully understood, but may involve action on carbonic anhydrase in smooth muscle or activation of large-conductance calcium-activated potassium (KCa) channels in smooth muscle. As an antihypoglycaemic agent, Diazoxide inhibits insulin release from the pancreas, likely by opening potassium channels in pancreatic beta-cell membranes.

Pharmacodynamics: Diazoxide is a potassium channel activator. It increases cell membrane permeability to potassium ions, leading to relaxation of smooth muscle. This inhibits voltage-gated calcium channel activity, thereby reducing action potential generation.

For both adults and children: a starting oral dose of 5 mg/kg body weight divided into 2 or 3 equal doses per 24 hours will establish the patient's response and thereafter the dose can be increased until the symptoms and blood glucose level respond satisfactorily. Regular determinations of the blood glucose in the initial days of treatment are essential. The usual maintenance dose is 3–8 mg/kg/day given in two or three divided doses.

Patients with renal impairment: Reduced doses may be required in patients with impaired renal function.

In children with leucine-sensitive hypoglycaemia: A dosage range of 15–20 mg/kg/day is suggested.

In adults with benign or malignant islet-cell tumours producing large quantities of insulin: High dosages of up to 1,000 mg per day have been used.

Drugs whose effects may be potentiated by Diazoxide include oral diuretics, antihypertensive agents, and anticoagulants. Phenytoin levels should be monitored, as an increased dose may be required when used concurrently with Diazoxide. The risk of hyperglycaemia may be increased when Diazoxide is given with corticosteroids or oestrogen–progestogen combinations.

In the treatment of hypoglycaemia, Diazoxide is contraindicated in all cases that are suitable for surgery or other specific therapy. It is also contraindicated in patients with hypersensitivity to Diazoxide or other thiazides.

Adverse reactions may include thrombocytopenia, pancreatitis, hypotension, diarrhoea, and heart failure.

Pregnancy: Animal studies with oral Diazoxide have shown increased fetal resorption, delayed labour, and skeletal anomalies. Intravenous use in rabbits has shown skeletal and cardiac teratogenic effects. The drug crosses the placental barrier and may cause degeneration of fetal pancreatic beta cells. There are no adequate human studies; therefore, safety in pregnancy has not been established. Use should be restricted to situations where the mother’s life is at risk, and only when benefits outweigh potential fetal risks. Prolonged use during pregnancy has been associated with neonatal alopecia.

Nursing mothers: It is not known whether Diazoxide passes into breast milk. Because many drugs are excreted in milk and may cause adverse effects in nursing infants, a decision should be made whether to discontinue breastfeeding or discontinue the drug, considering its importance to the mother.

During treatment of hypoglycaemia, blood pressure should be regularly monitored. Sodium and water retention may require treatment with oral diuretics such as frusemide or ethacrynic acid.

When diuretics are used, both hypotensive and hyperglycaemic effects of Diazoxide may be enhanced, and dosage adjustment may be necessary. In severe renal failure, urinary output should be maintained above 1 litre per day. Hypokalaemia should be prevented with adequate potassium supplementation.

Diazoxide should be used cautiously in patients with cardiac failure or reduced cardiac reserve, as fluid retention may worsen heart failure. It should also be used carefully in patients with impaired cardiac or cerebral circulation, aortic coarctation, aortic stenosis, arteriovenous shunts, or other cardiovascular conditions where increased cardiac output may be harmful.

Caution is advised in patients with hyperuricaemia or gout, with monitoring of serum uric acid levels.

With long-term therapy, regular haematological monitoring is required to detect changes in white blood cell and platelet counts. In children, growth, bone development, and psychological maturation should be regularly assessed.

Due to strong plasma protein binding, cautious dosing is required in patients with low plasma protein levels.

Overdose may cause hyperglycaemia. Severe cases may require insulin, while mild cases may respond to oral hypoglycaemic agents. Hypotension may be treated with intravenous fluids, and in severe cases, sympathomimetic agents may be required.

Combination oral hypoglycaemic preparations

Store below 30°C. Keep in the original container to protect from moisture. Keep out of reach and sight of children.