HYPERSTAT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for HYPERSTAT (HYPERSTAT).
Diazoxide is a thiazide-like nondiuretic benzothiadiazine derivative that acts as a direct vasodilator by opening ATP-sensitive potassium channels in vascular smooth muscle, leading to hyperpolarization and relaxation. It also inhibits insulin secretion by activating K+ channels in pancreatic beta cells.
| Metabolism | Primarily metabolized in the liver via oxidation and conjugation; less than 50% excreted unchanged in urine. Metabolites include 3-hydroxymethyl-diazoxide and its glucuronide conjugate. |
| Excretion | Renal excretion is the primary route of elimination, with approximately 50-70% of the dose excreted unchanged in urine. Biliary/fecal excretion accounts for less than 15%. |
| Half-life | The terminal elimination half-life is approximately 5-6 hours in adults with normal renal function. In patients with renal impairment, half-life can be prolonged up to 24-48 hours. |
| Protein binding | High protein binding, approximately 90-95%, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.5-1.0 L/kg, indicating distribution into extracellular fluid and some tissue binding. |
| Bioavailability | Bioavailability is 100% after intravenous administration. Oral bioavailability is not applicable as the drug is only available for intravenous use. |
| Onset of Action | Intravenous administration: Onset of blood pressure reduction occurs within 1-2 minutes, with maximal effect within 5-10 minutes. |
| Duration of Action | Duration of antihypertensive effect is 2-8 hours, but can be extended in patients with renal impairment or after multiple doses due to accumulation. |
Hypertension emergency: 150 mg IV bolus over 30 seconds, may repeat every 5-10 minutes as needed. Max dose: 300 mg. Alternatively, continuous IV infusion: 1-10 mg/min. Malignant hypertension: 100-200 mg IV bolus.
| Dosage form | INJECTABLE |
| Renal impairment | No specific GFR-based dose adjustment required. Use with caution in severe renal impairment; monitor for accumulation and hypotension. |
| Liver impairment | No specific Child-Pugh based adjustment. Use cautiously in severe hepatic impairment due to risk of hypotension and fluid retention. |
| Pediatric use | Hypertensive emergency: 1-2 mg/kg/dose IV bolus, may repeat every 10-15 minutes. Max single dose: 150 mg. Not established for continuous use in neonates. |
| Geriatric use | Use lower end of dosing range (50-100 mg IV bolus) due to increased sensitivity and risk of hypotension; monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for HYPERSTAT (HYPERSTAT).
| Breastfeeding | Diazoxide is excreted in human breast milk. The milk-to-plasma ratio is not well established. Because of the potential for serious adverse reactions in nursing infants (e.g., hyperglycemia or hypoglycemia, thrombocytopenia), a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | HYPERSTAT (diazoxide) is FDA Pregnancy Category C. In animal studies, diazoxide has been associated with fetal skeletal abnormalities, reduced fetal growth, and increased fetal mortality. In humans, there are no adequate well-controlled studies in pregnant women. However, diazoxide crosses the placenta and may cause fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism, and other adverse effects. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
Intravenous administration can cause excessive hypotension leading to cerebral and myocardial ischemia; therefore, use only in hospitalized patients under close medical supervision. Adjust dose carefully based on blood pressure response.
| Serious Effects |
["Hypersensitivity to diazoxide or thiazides","Aortic coarctation or arteriovenous shunt (relative contraindication due to risk of severe hypotension)","Compensatory hypertension (e.g., pheochromocytoma)"]
| Precautions | ["Can cause prolonged hypotension, requiring continuous monitoring","May precipitate angina or myocardial infarction in patients with coronary artery disease","Can cause sodium and water retention, leading to edema and congestive heart failure","May cause hyperglycemia, especially in diabetic patients","Monitor blood pressure, blood glucose, and fluid balance closely"] |
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| Fetal Monitoring | Monitor maternal blood glucose, blood pressure, and serum electrolytes regularly. In the fetus, monitor for signs of intrauterine growth restriction (ultrasound) and assess fetal well-being via non-stress tests or biophysical profiles as clinically indicated. Neonates should be monitored for hypoglycemia, hyperbilirubinemia, and thrombocytopenia after delivery. |
| Fertility Effects | Diazoxide may cause ovarian hyperstimulation syndrome, which can temporarily impair fertility. In animal studies, diazoxide has been reported to cause decreased fertility and increased preimplantation loss. The effect on human fertility is not fully known, but potential reversible effects on ovarian function should be considered. |