diazoxide
Hyperstat IV, Proglycem

Available forms
Available by prescription only
Capsules: 50 mg
Injection: 15 mg/ml in 20-ml ampule
Oral suspension: 50 mg/ml in 30-ml bottle

Indications and dosages
 Hypertensive crisis. Adults and children: 1 to 3 mg/kg I.V. (to a maximum of 150 mg) q 5 to 15 minutes until blood pressure is reduced adequately. May repeat dose at 4- to 24-hour intervals to maintain blood pressure at pretreatment levels or until P.O. medication can be used. Don’t use for longer than 10 days.
 Hypoglycemia from hyperinsulinism. Adults and children: Usual dosage is 3 to 8 mg/kg P.O. daily divided into two or three equal doses.
Infants and newborns: Usual dosage is 8 to 15 mg/kg P.O. daily divided into two or three equal doses.

Pharmacodynamics
Antihypertensive action: Diazoxide directly relaxes arteriolar smooth muscle, causing vasodilation and reducing peripheral vascular resistance, thus reducing blood pressure.
Antihypoglycemic action: Diazoxide increases blood glucose levels by inhibiting pancreatic secretion of insulin, by stimulating catecholamine release, or by increasing hepatic release of glucose.

Pharmacokinetics
Absorption: After oral administration, hyperglycemic effect begins in 1 hour.
Distribution: Distributed throughout the body; highest level is found in kidneys, liver, and adrenal glands; diazoxide crosses the placental and blood-brain barriers. Drug is about 90% protein-bound.
Metabolism: Metabolized partially in the liver.
Excretion: Excreted slowly by the kidneys. Duration of antihypertensive effect varies widely, ranging from 30 minutes to 72 hours (average 3 to 12 hours) after I.V. administration; after oral administration, antihypoglycemic effect persists for about 8 hours. Antihypertensive and antihypoglycemic effects may be prolonged in patients with renal dysfunction.

Contraindications and precautions
Parenteral form is contraindicated in patients hypersensitive to drug, other thiazides, or sulfonamide-derived drugs, and in the treatment of compensatory hypertension (such as that linked to coarctation of the aorta or arteriovenous shunt). Oral form is contraindicated in patients with functional hypoglycemia.
  Use cautiously in patients with uremia or impaired cerebral or cardiac function.

Interactions
Drug-drug. Antihypertensives: May potentiate antihypertensive effects, especially if given I.V. within 6 hours after patient has received another antihypertensive. Use together cautiously.
Diuretics: May potentiate antihypoglycemic, hyperuricemic, or antihypertensive effects of diazoxide. Monitor patient closely.
Insulin, oral antidiabetics: Insulin and oral antidiabetic requirements may change in previously stable diabetic patients. Monitor blood glucose levels.
Phenothiazines: May increase pharmacologic effects, including hyperglycemia. Monitor patient for increased or adverse effects.
Phenytoin: May increase metabolism and decrease plasma protein-binding of phenytoin. Monitor patient closely.
Thiazides: May enhance diazoxide effects. Use together cautiously.
Warfarin: May displace warfarin, bilirubin, or other highly protein-bound substances from protein-binding sites. Avoid use together.

Adverse reactions
CNS: dizziness, weakness; headache, malaise, anxiety, insomnia, paresthesia, fever (with oral form); headache, seizures, paralysis, cerebral ischemia, light-headedness, euphoria (with parenteral form).
CV: arrhythmias, tachycardia, hypotension, hypertension (with oral form); sodium and water retention, orthostatic hypotension, flushing, warmth, angina, myocardial ischemia, ECG changes, shock, MI (with parenteral form), sodium and fluid retention may precipitate heart failure.
EENT: diplopia, transient cataracts, blurred vision, lacrimation (with oral administration); optic nerve infarction (with parenteral form).
GI: abdominal discomfort, diarrhea; nausea, vomiting, anorexia, taste alteration (with oral form); nausea, vomiting, dry mouth, constipation (with parenteral form).
GU: azotemia, reversible nephrotic syndrome, decreased urine output, hematuria, albuminuria (with oral form).
Hematologic: leukopenia, thrombocytopenia, anemia, eosinophilia, excessive bleeding (with oral form).
Metabolic: sodium and fluid retention, ketoacidosis and hyperosmolar nonketotic syndrome, hyperuricemia, hyperglycemia.
Skin: hirsutism; rash, pruritus (with oral form); diaphoresis (with parenteral form); inflammation and pain from extravasation.

Effects on lab test results
• May increase glucose and uric acid levels.
• May decrease hemoglobin, hematocrit, and platelet, eosinophil, and WBC counts.

Overdose and treatment
Overdose causes mainly hyperglycemia; ketoacidosis and hypotension may occur.
 Treat acute overdose supportively and symptomatically. If hyperglycemia develops, give insulin and replace fluid and electrolyte losses; use vasopressors if hypotension fails to respond to conservative treatment. Hypotension can usually be controlled by the Trendelenburg maneuver. Prolonged monitoring may be needed because of the long half-life of diazoxide. Drug may be removed by hemodialysis.

Special considerations
• Diazoxide is used to treat only hypoglycemia resulting from hyperinsulinism; it isn’t used to treat functional hypoglycemia. It may be used temporarily to control preoperative or postoperative hypoglycemia in patients with hyperinsulinism.
• I.V. use of diazoxide is seldom needed for longer than 4 or 5 days. The use of 300-mg I.V. bolus push is no longer recommended. Switch to therapy with oral antihypertensives as soon as possible.
• Significant hypotension doesn’t occur after oral administration in doses used to treat hypoglycemia.
• Drug may be given by constant I.V. infusion (at 7.5 to 30 mg/minute) until adequate blood pressure reduction occurs.
• Diazoxide inhibits glucose-stimulated insulin release and may cause false-negative insulin response to glucagon.
• Monitor blood pressure and ECG continuously. Keep norepinephrine available.
• After I.V. injection, monitor blood pressure every 5 minutes for 15 to 30 minutes, then hourly when patient is stable. Discontinue if severe hypotension develops or if blood pressure continues to decrease 30 minutes after drug infusion; keep patient recumbent during this time and have norepinephrine available. Monitor I.V. site for infiltration or extravasation.
• Intake and output must be monitored carefully. If fluid or sodium retention develops, diuretics may be given 30 to 60 minutes after diazoxide. Patient must be recumbent for 8 to 10 hours after diuretic administration.
• Monitor daily blood glucose and electrolyte levels, watching diabetic patients closely for severe hyperglycemia or hyperglycemic hyperosmolar nonketotic coma; also monitor daily urine glucose and ketone levels, intake and output, and weight. Check serum uric acid levels frequently.
Pregnant patients
• Don’t use drug during labor and delivery because drug crosses the placental barrier. Maternal hypotension and fetal bradycardia have been reported. Neonatal hyperglycemia has also occurred. I.V. administration may stop uterine contractions and an oxytocic would be needed.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk; an alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Use cautiously in children.
Geriatric patients
• Elderly patients may have a more pronounced hypotensive response.

Patient education
• Explain that orthostatic hypotension can be minimized by rising slowly and avoiding sudden position changes.
• Tell patient to report adverse effects immediately, including pain and redness at injection site, which may indicate infiltration.
• Instruct patient to check weight daily and report gains of more than 5 lb (2.3 kg) per week; diazoxide causes sodium and water retention.
• Reassure patient that excessive hair growth is a common reaction that subsides when treatment is completed.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use