DIAZOXIDE
Clinical safety rating
cautionComprehensive clinical and safety monograph for DIAZOXIDE (DIAZOXIDE).
Diazoxide is a potassium channel activator that opens ATP-sensitive potassium channels in pancreatic beta cells, inhibiting insulin secretion. It also causes peripheral vasodilation by activating potassium channels in vascular smooth muscle.
| Metabolism | Hepatic metabolism with excretion of metabolites in urine and bile. Minor metabolism via hydroxylation and glucuronidation. |
| Excretion | Renal: ~50% unchanged; minor biliary/fecal excretion. |
| Half-life | Terminal half-life: 20-36 hours (adults), 9-24 hours (children). Context: shorter after IV bolus due to redistribution; prolonged in renal impairment. |
| Protein binding | >90% bound to serum albumin. |
| Volume of Distribution | 0.2-0.4 L/kg; small Vd indicates limited extravascular distribution. |
| Bioavailability | Oral: ~100% (well absorbed); IV: 100%. |
| Onset of Action | IV: 1-5 minutes (rapid vasodilation). Oral: 30-60 minutes (hyperglycemic effect). |
| Duration of Action | IV: 2-6 hours (antihypertensive effect); Oral: 4-8 hours (sustained glucose elevation up to 12 h). |
| Molecular Weight | 280.26 |
Hypertension: 1-3 mg/kg IV bolus, up to 150 mg, repeated every 5-15 minutes to achieve desired blood pressure. Hyperinsulinemic hypoglycemia: 3-8 mg/kg/day PO divided every 8-12 hours.
| Dosage form | Injectable |
| Renal impairment | No specific GFR-based dose adjustments are required; however, accumulation may occur in severe renal impairment. Use with caution and monitor blood pressure and electrolytes. |
| Liver impairment | No specific Child-Pugh based dose adjustments available. Use with caution in hepatic impairment due to potential for increased adverse effects. |
| Pediatric use | Hyperinsulinemic hypoglycemia: 10-25 mg/kg/day PO divided every 8-12 hours. Hypertensive emergency: 1-3 mg/kg IV bolus, may repeat every 5-15 minutes. |
| Geriatric use | Initial dose reduction recommended due to increased sensitivity to antihypertensive effects and higher risk of hypotension and electrolyte disturbances. Start at lower end of dosing range and titrate carefully. |
| 1st trimester | Diazoxide crosses the placenta. In animal studies, it has been associated with fetal skeletal abnormalities and pancreatic islet cell tumors. Human data are limited. Use only if clearly needed. |
| 2nd trimester | Diazoxide crosses the placenta. Risk of fetal hypertrichosis, pancreatic islet cell hyperplasia, and neonatal hyperglycemia. Use only if potential benefit justifies potential risk. |
| 3rd trimester | Diazoxide crosses the placenta. May cause prolonged neonatal hyperbilirubinemia, hyperglycemia, and thrombocytopenia. Avoid use near term if possible. |
Clinical note
Comprehensive clinical and safety monograph for DIAZOXIDE (DIAZOXIDE).
| Placental transfer | Diazoxide crosses the human placenta readily. It has been detected in cord blood at concentrations similar to maternal serum. Animal studies show significant placental transfer. |
| Breastfeeding | Diazoxide is excreted into human milk. Potential for adverse effects in the nursing infant, including hyperglycemia, hypertrichosis, and developmental concerns. Use with caution; monitor infant for signs of hyperglycemia. |
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | In animals, diazoxide is teratogenic at high doses, producing fetal abnormalities including skeletal and visceral malformations. Human data are limited; however, case reports have described fetal/neonatal adverse effects such as hypertrichosis, alopecia, and transient hyperglycemia after in utero exposure. Use in pregnancy only if clearly needed, weighing benefit versus fetal risk. There is no clear evidence of increased risk for major birth defects, but data are insufficient to rule out risk. |
| Fetal Monitoring | Monitor maternal blood glucose, blood pressure, and electrolytes (especially sodium and potassium) regularly. Assess fetal growth and well-being via ultrasound and nonstress tests as appropriate. Monitor neonatal blood glucose and signs of hypertrichosis or electrolyte disturbances after delivery. |
| Fertility Effects | No well-controlled studies on fertility in humans. In animal studies, high doses may impair fertility. In humans, potential for reversible ovarian cyst formation and menstrual irregularities has been reported. Clinical significance is unknown. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to diazoxide or any excipientsFunctional hypoglycemia (e.g., insulinoma unless surgical candidate)Concurrent use with thiazide diuretics (may potentiate hyperglycemia)Severe hypotension (for intravenous use)
| Precautions | Fluid retention and edema, especially in patients with cardiac or renal impairment, Hyperglycemia (may require insulin or oral hypoglycemics), Hypotension (with IV administration), Cerebral ischemia or infarction (with rapid IV injection), Tachycardia and arrhythmias |
| Food/Dietary | Avoid grapefruit juice; may increase diazoxide levels. Limit high-sodium foods to reduce fluid retention. Alcohol may enhance hypotensive effects. |
| Clinical Pearls | Diazoxide is a potassium channel opener used for hypertensive emergencies and hypoglycemia due to hyperinsulinism. Administer intravenously for hypertension; oral form used for hypoglycemia. Rapid injection may cause hypotension; monitor blood pressure closely. Can cause sodium and water retention; co-administer with a diuretic. Contraindicated in patients with hypersensitivity to thiazides or sulfonamides. |
| Patient Advice | Take oral diazoxide exactly as prescribed, usually every 8-12 hours. · Monitor blood glucose regularly, especially if diabetic. · Report symptoms of fluid retention (swelling, weight gain) or hypotension (dizziness, fainting). · Avoid alcohol and limit sodium intake. · Do not stop abruptly; taper under medical supervision. |
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