HYPERSTAT
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 230.7 |
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 | Avoid use due to risk of fetal abnormalities based on animal studies. |
| 2nd trimester | Use only if clearly needed; may cause fetal hypotension and decreased placental perfusion. |
| 3rd trimester | Use only if clearly needed; may cause fetal bradycardia and hypoglycemia. |
Clinical note
Comprehensive clinical and safety monograph for HYPERSTAT (HYPERSTAT).
| Placental transfer | Crosses placenta; detectable in fetal serum after maternal administration. |
| Breastfeeding | Diazoxide is excreted into breast milk; potential for infant hypoglycemia and hypertrichosis. Use with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 |
Acute aortic dissectionCerebrovascular accidentCompensatory hypertension due to arteriovenous shunt or coarctation of aortaHypersensitivity to thiazides or sulfonamide derivativesSevere hypotension
| 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 |
| Food/Dietary | Avoid high-sodium foods as they can counteract the antihypertensive effect. Limit caffeine intake as it may increase blood pressure. No specific food restrictions beyond maintaining a balanced diet; however, monitor carbohydrate intake due to hyperglycemia risk. |
| Clinical Pearls | Hyperstat (diazoxide) is a potent vasodilator used for hypertensive emergencies, but it can cause severe hypotension; always have IV fluids ready. It also inhibits insulin release, causing hyperglycemia, so monitor blood glucose closely. Rapid injection over 30 seconds or less is required to achieve effect; slower infusion reduces efficacy. |
| Patient Advice | This medication will rapidly lower your blood pressure; you may feel dizzy or lightheaded while lying down. · Report symptoms of low blood sugar such as shaking, sweating, or confusion. · Avoid alcohol because it can worsen low blood pressure and dizziness. · You should not operate machinery or drive until you know how this drug affects you. · This drug can cause fluid retention; inform your doctor if you notice swelling in your feet or legs. |
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