diazoxide (Rx)

Frequency Not Defined

Angina

Cardiac arrest

Anxiety

Fever

Polyneuritis

CHF

Hypotension

Palpitation

Tachycardia

Dizziness

Anorexia

Abdominal pain

Constipation

Diarrhea

Loss of taste

Nausea

Vomiting

Diabetic ketoacidosis

Hirsutism

Scalp hair loss

Hyperglycemia

Sodium and fluid retention

Postmarketing reports

Pulmonary hypertension in neonates and young infants

Contraindications

Hypersensitivity to diazoxide, thiazides, or sulfonamide derivatives

Cautions

Use caution in coronary or cerebral insufficiency, DM, extravasation, heart failure (may increase fluid retention), cardiovascular insufficiency, gout, hypotension, hypokalemia, liver disease, renal dysfunction

Pregnancy

Compensatory HTN (aortic coarctation, arteriovenous shunt)

Ineffective in pheochromocytoma

Nonketotic hyperosmolar coma may occur during treatment; transient cataracts reported

May displace bilirubin from albumin; use caution in newborns with hyperbilirubinemia

The antidiuretic property of diazoxide may lead to significant fluid retention, which in patients with compromised cardiac reserve, may precipitate congestive heart failure; the fluid retention will respond to conventional therapy with diuretics

Concomitantly administered thiazides may potentiate the hyperglycemic and hyperuricemic actions of diazoxide

Ketoacidosis and nonketotic hyperosmolar coma reported in patients treated with recommended doses usually during intercurrent illness; prompt recognition and treatment essential and prolonged surveillance following the acute episode necessary because of long drug half-life of approximately 30 hours; occurrence of these serious events may be reduced by careful education of patients regarding monitoring urine for sugar and ketones and for prompt reporting of abnormal findings and unusual symptoms to healthcare provider

Effects of diazoxide on the hematopoietic system and the level of serum uric acid kept in mind; the latter should be considered particularly in patients with hyperuricemia or a history of gout

Antihypertensive effect of other drugs may be enhanced by diazoxide; should keep this in mind when administering it concomitantly with antihypertensive agents

Because of protein binding, administration of diazoxide with coumarin or its derivatives may require reduction in dosage of anticoagulants

Pulmonary hypertension in newborns and infants

• July 16, 2015: FDA warns clinicians to watch for signs of pulmonary hypertension in infants treated for hypoglycemia with diazoxide and discontinue the drug if symptoms appear
• There have been 11 cases identified since the drug was approved (1973) and once diazoxide was discontinued, the symptoms resolved
• Signs of respiratory distress include flaring nostrils, grunting, unusual chest movements, rapid breathing, difficulty feeding, or a bluish tint to the lips or skin
• Monitoring is especially important for infants who have other risk factors for pulmonary hypertension (eg, meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, and congenital heart disease)

Pregnancy Category: C

Lactation: Excretion in milk unknown; not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Inhibits pancreatic insulin release resulting increased blood glucose; activates potassium channels

Relaxes smooth muscle to decrease PVR, increases HR & CO; precise mechanism of hypotensive effect not fully elucidated; antagonism of calcium may be involved

Pharmacokinetics

Half-Life: 9-24 hr (children); 24-36 hr (adults), increases in patients with renal impairment

Duration: varies greatly, may last to 3-12 hr

Protein binding: 90%

Metabolism: In liver by oxidation and sulfate conjugation

Renal Clearance: 4-5 mL/min

Excretion: urine by glomerular filtration as unchanged drug and metabolites

Dialyzable: HD: yes, PD: yes; no supplemental dose is required

Excretion: Urine