Eudaxen

Approved Indications:

• Management of hypoglycemia due to hyperinsulinism:
• Congenital hyperinsulinism in neonates and infants.
• Insulinoma-induced hypoglycemia (adult and pediatric patients).
• Hypertensive emergencies:
• Short-term control of hypertensive crises, particularly in patients with malignant hypertension unresponsive to other therapies.

Off-label / Clinically Accepted Uses:

• Prevention and treatment of hypoglycemia associated with insulin secretagogue overdose.
• Adjunctive therapy for hyperinsulinemic hypoglycemia in adults.
• Occasionally used in certain cases of insulin resistance.

Route: Oral administration.

Adults:

• For hypoglycemia: Initial dose 3–8 mg/kg/day divided into 2–3 doses; maintenance doses adjusted to clinical response, generally 50–300 mg/day.
• For hypertensive emergencies: Initial dose 3 mg/kg as a slow intravenous infusion; maintenance infusion adjusted per blood pressure response (typical doses 50–300 mg/day).

Pediatrics:

• Hypoglycemia: Starting dose 8 mg/kg/day orally, divided 2–3 times daily; titrated based on blood glucose levels and clinical response.

Elderly:

• Use with caution; start at the lower end of dosing range due to increased sensitivity and comorbidities.

Special Populations:

• Renal impairment: Dose adjustment recommended; monitor for fluid retention and electrolyte disturbances.
• Hepatic impairment: Use with caution; possible altered metabolism.

Administration Notes:

• Oral doses should be taken with food to reduce gastrointestinal upset.
• Intravenous administration should be slow and under strict monitoring for blood pressure and cardiac status.
• Monitor blood glucose closely during therapy and adjust dose accordingly.
• Discontinue gradually to prevent rebound hypoglycemia.

Diazoxide acts primarily by opening ATP-sensitive potassium (K_ATP) channels on pancreatic beta-cell membranes. This hyperpolarizes the beta cells, inhibiting calcium influx through voltage-dependent calcium channels, which in turn suppresses insulin secretion. By reducing insulin release, diazoxide effectively raises blood glucose levels in hyperinsulinemic states. Additionally, diazoxide causes direct arteriolar vasodilation by opening vascular smooth muscle K_ATP channels, resulting in decreased peripheral vascular resistance and blood pressure reduction in hypertensive emergencies.

• Absorption: Well absorbed orally with peak plasma concentrations reached within 1–2 hours.
• Distribution: Widely distributed; approximately 90% protein bound.
• Metabolism: Partially metabolized by the liver.
• Elimination: Primarily excreted unchanged via the kidneys; elimination half-life approximately 24–36 hours.
• Onset: Oral: 1–2 hours; IV: within minutes.
• Duration: Effects on insulin secretion may last 8–12 hours after a single dose.

• Pregnancy: Category C (FDA). Animal studies have shown adverse effects on the fetus, but no adequate human studies are available. Use only if potential benefits justify the potential risk to the fetus.
• Lactation: Unknown whether diazoxide is excreted in human milk. Caution is advised when administered to nursing mothers.
• Note: Careful consideration required before use in pregnancy and breastfeeding; monitor maternal and fetal/neonatal blood glucose closely.

• Antihypoglycemic agent
• Potassium channel opener
• Vasodilator (for hypertensive emergencies)

• Known hypersensitivity to diazoxide or any component of the formulation.
• Severe coronary artery disease or congestive heart failure.
• Pulmonary hypertension.
• Hypersensitivity to sulfonamides (cross-reactivity possible).
• Marked fluid retention or severe edema.
• Pheochromocytoma (unless treated concurrently with alpha-blockers).

• Monitor for fluid retention and signs of congestive heart failure; may cause or worsen edema.
• Use cautiously in patients with cardiac disease or renal impairment.
• Risk of hyperglycemia and consequent osmotic diuresis; monitor serum glucose regularly.
• Can cause thrombocytopenia and leukopenia; monitor blood counts during prolonged therapy.
• Potential for increased risk of infections due to immunosuppressive effects.
• Not recommended for abrupt discontinuation; taper dose to avoid rebound hypoglycemia.
• Caution in patients with pheochromocytoma due to risk of hypertensive crisis without alpha-blockade.
• Monitor blood pressure closely when used for hypertensive emergencies.

Common:

• Hyperglycemia
• Fluid retention and peripheral edema
• Nausea and vomiting
• Headache
• Hyperuricemia

Serious/Rare:

• Congestive heart failure exacerbation
• Thrombocytopenia
• Leukopenia/neutropenia
• Hyperosmolar hyperglycemic state
• Pulmonary hypertension
• Allergic reactions (rash, angioedema)

• Insulin and oral hypoglycemics: Diazoxide antagonizes their effects; may require dose adjustments.
• Diuretics: May exacerbate fluid retention; careful monitoring needed.
• Antihypertensives: Additive hypotensive effects may occur.
• Beta-blockers: Combined use may alter glucose metabolism and mask hypoglycemia symptoms.
• Lithium: Possible increased serum lithium levels.
• CYP450 enzyme interactions: Limited data, but metabolism may be affected by hepatic enzyme inducers or inhibitors.

• Recent guidelines emphasize careful glucose and fluid status monitoring in patients receiving diazoxide, particularly in neonates with congenital hyperinsulinism.
• Updated recommendations caution against use in patients with significant cardiac or pulmonary comorbidities.
• The use of diazoxide as a vasodilator in hypertensive emergencies is generally reserved for refractory cases, with close hemodynamic monitoring.
• FDA safety communications advise vigilance for hematologic adverse effects during prolonged treatment.

• Store at controlled room temperature: 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Do not freeze.
• Store oral tablets and injectable formulations separately according to manufacturer instructions.
• Keep out of reach of children.