Diazoxide (Monograph)

Brand name: Proglycem
Drug class: Antihypoglycemic Agents, Miscellaneous
- Hyperglycemic Agents
VA class: CV490
CAS number: 364-98-7

Medically reviewed by Drugs.com on Apr 5, 2024. Written by ASHP.

Introduction

Nondiuretic antihypoglycemic agent; structurally related to the thiazide diuretics.

Uses for Diazoxide

Hypoglycemia

Adults: Used orally in the management of hypoglycemia caused by hyperinsulinism associated with inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy.

Infants and children: Used orally in the management of hypoglycemia associated with leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis.

Adults and children: May be used preoperatively as a temporary measure, and postoperatively if hypoglycemia persists.

Should be used only after diagnosis of hypoglycemia caused by one of the above conditions has been definitely established and when specific medical or surgical management has been unsuccessful or is not feasible.

Diazoxide Dosage and Administration

General

• Since repeated administration of diazoxide may cause sodium and water retention, administer a diuretic to patients receiving multiple doses of the drug.

Hypoglycemia

• Individualize oral dosage based on severity of condition, blood glucose concentration, and clinical response of patient.

• Observe patients closely when treatment is initiated. Monitor blood glucose concentrations until patient’s condition has stabilized; usually requires several days.

• If hyperglycemia or glycosuria occurs, reduction in dosage may be required to avoid progression to ketoacidosis or hyperosmolar coma.

• Discontinue drug if not effective after 2–3 weeks. In patients who respond to diazoxide, therapy must be continued for several years. The drug may be discontinued when insulin-glucose ratios and insulin responses to provocative tests are normal.

Administration

Administer orally.

Has been administered IV for management of severe hypertension; however, a parenteral preparation no longer is commercially available in US.

Dosage

Pediatric Patients

Hypoglycemia

Oral

Children: Usual initial dosage is 3 mg/kg daily given in 3 equal doses every 8 hours.

Children: Usual maintenance dosage is 3–8 mg/kg daily given in 2 or 3 divided doses every 12 or 8 hours, respectively.

Refractory hypoglycemia in children: May require high doses; dosages as high as 10–15 mg/kg daily have been used.

Infants and neonates: Usual initial dosage is 10 mg/kg daily given in 3 equal doses every 8 hours.

Infants and neonates: Usual maintenance dosage is 8–15 mg/kg daily given in 2 or 3 equal doses every 12 or 8 hours, respectively.

Adults

Hypoglycemia

Oral

Usual initial dosage: 3 mg/kg daily given in 3 equal doses every 8 hours (i.e., approximately 200 mg daily for an average adult).

Usual maintenance dosage: 3–8 mg/kg daily given in 2 or 3 equal doses every 12 or 8 hours, respectively.

Refractory hypoglycemia: May require high doses; dosages as high as 10–15 mg/kg daily have been used.

Special Populations

Renal Impairment

Patients with Hypoglycemia

Oral

Since plasma half-life is prolonged with renal impairment, consider reduced dosage.

Related/similar drugs

hydralazine, enalapril, labetalol, glucagon, Apresoline, methyldopa, Vasotec

Cautions for Diazoxide

Contraindications

• Hypersensitivity to the drug, other thiazide derivatives, or other sulfonamide-derived agents.

• Functional hypoglycemia.

Warnings/Precautions

Warnings

Pulmonary Hypertension

Pulmonary hypertension reported in neonates and infants.

Monitor infants and neonates for manifestations of respiratory distress (e.g., tachypnea, flaring nostrils, grunting, chest wall retractions, feeding intolerance, cyanosis), particularly in those with risk factors for pulmonary hypertension (e.g., meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, congenital heart disease). (See Advice to Patients.) Discontinue therapy if pulmonary hypertension occurs.

Cardiovascular Effects

Sodium and water retention occurs frequently in patients (adults and young infants), and may result in edema, weight gain, and CHF (especially in uremic patients). (See Renal Impairment under Cautions.)

Hyperglycemia

Monitor blood glucose concentrations. In patients receiving oral therapy for the treatment of hypoglycemia, monitor blood glucose concentrations carefully until the patient’s condition has stabilized.

Usually mild and subsides without treatment. May require administration of oral hypoglycemic agents or insulin, especially in diabetic patients or those receiving repeated doses of diazoxide.

Ketoacidosis and nonketotic hyperosmolar coma reported with recommended oral dosage, usually during intercurrent illness.

If ketoacidosis occurs, administer insulin and restore fluid and electrolyte balance immediately.

Sensitivity Reactions

Rash, leukopenia, fever.

General Precautions

Metabolic and Electrolyte Effects

Repeated administration may cause sodium and fluid retention. (See Cardiovascular Effects under Cautions.)

Administer a diuretic to patients receiving multiple doses of diazoxide. Consider the possibility of potentiation of hypotensive, hyperglycemic, and hyperuricemic effects in patients receiving concomitant diuretic therapy.

Administer with caution to patients in whom retention of sodium and water may be hazardous (e.g., those with impaired cardiac reserve).

Exercise caution when administering to uremic patients, since these patients may experience a greater hypotensive effect. Hematologic monitoring may be advisable in patients who receive the drug for longer than a few days; monitor serum uric acid concentration in patients with hyperuricemia or a history of gout.

Specific Populations

Pregnancy

Category C. May produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism.

IV diazoxide (parenteral preparation no longer commercially available in US) has caused cessation of uterine contractions during labor; administration of oxytocic agents may be required. Caution advised if oral diazoxide administered during labor and delivery.

Lactation

Not known whether diazoxide is distributed into milk. Discontinue nursing or the drug.

Renal Impairment

Nondiabetic hypertensive patients with impaired renal function may develop diabetic ketoacidosis following multiple doses of diazoxide. Observe patients carefully for possible development of severe hyperglycemia.

Avoid prolonged hypotension since it may aggravate preexisting renal failure.

Monitor serum electrolyte concentrations in patients with renal impairment. Such patients may require potent diuretics such as furosemide or ethacrynic acid rather than thiazide diuretics to manage sodium and fluid retention.

Common Adverse Effects

Sodium and fluid retention, tachycardia, palpitations, increased uric acid concentrations, hyperglycemia or glycosuria, GI intolerance, hirsutism, thrombocytopenia.

Drug Interactions

Specific Drugs and Laboratory Tests

Diazoxide Pharmacokinetics

Absorption

Bioavailability

Peak blood concentrations attained in 4 hours following oral administration as a suspension.

Duration

Glycemic effect begins within 1 hour and lasts approximately ≤8 hours in patients with normal renal function.

Plasma Concentrations

Minimum blood diazoxide concentrations of 10 mcg/mL appear to be necessary for initial hypotensive effects.

Distribution

Extent

In animals, distributes into kidneys with relatively high concentrations in liver and adrenal glands.

Crosses placenta and blood-brain barrier. Not known whether the drug is distributed into milk.

Plasma Protein Binding

>90% bound.

May displace bilirubin from albumin; may produce neonatal hyperbilirubinemia.

Special Populations

Diazoxide is less bound to cord plasma proteins than to adult plasma proteins.

In patients with chronic uremia, there is a substantial reduction of plasma protein binding, probably resulting from decreased serum albumin in these patients.

Elimination

Metabolism

Partially metabolized by oxidation and sulfate conjugation and excreted slowly in urine by glomerular filtration as unchanged drug and metabolites.

Elimination Route

In one patient, 2% of an orally administered dose of diazoxide was recovered in feces.

Half-life

21–48 hours in adults with normal renal function. The high degree of protein binding is responsible for the prolonged half-life.

Special Populations

In pediatric patients, terminal elimination half-life may be somewhat shorter than in adults.

In patients with renal impairment, half-life is prolonged in proportion to decreases in Cl_cr. Diazoxide and its metabolites are removed by hemodialysis and peritoneal dialysis, but dialysance is relatively low because of extensive protein binding.

Stability

Storage

Oral

Suspension

25°C (may be exposed to 15–30°C); protect from light. Should not use darkened oral suspensions since they may be subpotent.

Actions

• Increases blood glucose concentration by inhibiting pancreatic insulin secretion, stimulating release of catecholamines, and/or increasing hepatic release of glucose. Markedly inhibits glucose- and glucagon-induced insulin secretion.

• Decreases cortisol secretion.

• Increases plasma free fatty acid concentrations.

• Reduces peripheral vascular resistance and BP as a result of a direct vasodilatory effect on smooth muscle in peripheral arterioles; hypotensive effect usually not marked with oral administration. Increases heart rate, cardiac output, and left ventricular ejection rate, probably as a result of a reflex response to decreased peripheral vascular resistance.

• Causes sodium and water retention and decreased urinary output, which can result in expansion of plasma and extracellular fluid volume. Reduces excretion of potassium, chloride, bicarbonate, and uric acid.

• Inhibits uterine contractions.

Advice to Patients

• Importance of taking oral diazoxide regularly and of not skipping doses or taking extra doses.

• Importance of not sharing the drug with others.

• Importance of following dietary instructions.

• In patients treated for hypoglycemia, importance of testing blood and urine for glucose and ketones regularly and of reporting results to their clinicians.

• In patients being treated for hypoglycemia, importance of reporting any signs or symptoms of adverse effects (i.e., increased urinary frequency, increased thirst, fruity breath odor).

  Importance of advising parents or caregivers to monitor neonates and infants for manifestations of respiratory distress (e.g., tachypnea, flaring nostrils, grunting, chest wall retractions, cyanosis) and to immediately contact a clinician if such symptoms occur.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• Should you use a diuretic with diazoxide?
• How does diazoxide (Proglycem) cause hyperglycemia?
• Is diazoxide a vasodilator?
• How does diazoxide slow insulin?

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