DIAZOXIDE
Clinical safety rating: caution
Comprehensive 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). |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIAZOXIDE (DIAZOXIDE).
| Breastfeeding | Diazoxide is excreted into human breast milk; the milk-to-plasma ratio is approximately 0.17–0.23 based on limited data. Milk concentrations are low relative to therapeutic doses, but potential for infant toxicity (e.g., hyperglycemia, hypertrichosis) exists. Caution advised; if used, monitor infant for signs of hyperglycemia or other adverse effects. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to diazoxide or thiazides","Functional hypoglycemia (e.g., reactive hypoglycemia)","Severe hypotension","Cardiogenic shock"]
| 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"] |
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| 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. |