Version October 2023
Congenital hyperinsulinism (eg, persistent hyperinsulinemic hypoglycemia of infancy): Note: Pulmonary hypertension has been observed in neonates while on diazoxide therapy; most frequently reported at doses ≥10 mg/kg/day; monitor neonates closely while on therapy; consider baseline and periodic echocardiogram (Timlin 2017)
Neonates: Oral: Initial: 10 mg/kg/day in divided doses every 8 hours; gradually titrate; due to the long half-life it may take several days (eg, 5 days) to assess dose-response (Eichenwald 2017); usual range: 5 to 15 mg/kg/day in divided doses every 8 to 12 hours (Demirbilek 2017; Hoe 2006; Hussain 2004; Kapoor 2009). Note: Use in combination with chlorothiazide to minimize fluid retention and during initial management (eg, acute situations), concomitant IV dextrose infusion used. Dosing should be individualized to patient response to achieve and maintain target serum glucose concentrations (typically >70 mg/dL) (Sperling 2014). Use the least amount of drug that achieves the desired clinical and laboratory results. Positive therapeutic responses are seen in 50% of neonates within 48 to 72 hours; after 5 days of therapy, evaluate overall response (Eichenwald 2017; Sperling 2014). The manufacturer recommends discontinuing if no effect after 2 to 3 weeks.
Dosing adjustment in renal impairment: Half-life may be prolonged with renal impairment; a reduced dose may be necessary. Use with caution and monitor blood glucose and fluid status closely.
Hyperinsulinemic hypoglycemia: Note: Diazoxide may not be effective for all types of hyperinsulinemic hypoglycemia. Dose should be individualized and may vary based on the cause (eg, genetic mutation, insulinomas) and severity of the hypoglycemic condition, blood glucose concentration, and clinical response of patient. Use the least amount of drug that achieves the desired clinical and laboratory results. For some hyperinsulinemic conditions, onset of action may vary; the manufacturer recommends discontinuation if no effect after 2 to 3 weeks; however, this may vary based on condition being treated and this timeframe. Often used in combination with a thiazide diuretic to ameliorate possible fluid retention that may occur with diazoxide therapy (Shah 2017).
Infants: Oral: Initial: 5 mg/kg/day in divided doses every 8 hours; gradually titrate; due to the long half-life it may take several days (eg, 5 days) to assess dose-response (Eichenwald 2017); usual range: 8 to 15 mg/kg/day in divided doses every 8 to 12 hours; reported range: 5 to 20 mg/kg/day in divided doses every 8 to 12 hours (Demirbilek 2017; Kapoor 2009; Shah 2017). Note: Pulmonary hypertension has been observed in neonates and infants while on diazoxide therapy; most frequently reported at doses ≥10 mg/kg/day; monitor neonates and infants closely while on therapy; consider baseline and periodic echocardiogram (Timlin 2017).
Children and Adolescents: Oral: Initial: 5 mg/kg/day in divided doses every 8 hours; reported range: 5 to 20 mg/kg/day in divided doses every 8 to 12 hours; usual range: 3 to 8 mg/kg/day in divided doses every 8 to 12 hours (Demirbilek 2017; Shah 2017; Sperling 2014).
All patients: Half-life may be prolonged with renal impairment; a reduced dose should be considered.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Diazoxide: Drug information")
Hyperinsulinemic hypoglycemia:
Note: For use when other specific medical therapy or surgical management for hypoglycemia is unsuccessful or is not feasible.
Oral: Initial: 3 mg/kg/day divided into 3 equal doses every 8 hours; dosing range: 3 to 8 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours. Adjust dose until the desired clinical and laboratory effects are produced. Note: Patients with refractory hypoglycemia may require higher doses. Discontinue if no effect after 2 to 3 weeks.
There are no dosage adjustments provided in the manufacturer's labeling; consider a dosage reduction (half-life may be prolonged).
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Hypertension (transient), hypotension, palpitations, tachycardia
Dermatologic: Cutaneous candidiasis, loss of scalp hair, pruritus, skin rash
Endocrine & metabolic: Albuminuria, diabetes mellitus with hyperosmolar coma (nonketotic), diabetic ketoacidosis, fluid retention, galactorrhea not associated with childbirth, hirsutism, hyperglycemia, increased uric acid, sodium retention
Gastrointestinal: Abdominal pain, acute pancreatitis, ageusia (transient), anorexia, diarrhea, intestinal obstruction, nausea, pancreatic necrosis, vomiting
Genitourinary: Azotemia, decreased urine output, glycosuria, hematuria, lump in breast (enlargement)
Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, decreased serum immunoglobulins (IgG), eosinophilia, hemorrhage (excessive), lymphadenopathy, neutropenia (transient)
Hepatic: Increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Infection: Herpes virus infection
Nervous system: Anxiety, asthenia, dizziness, extrapyramidal reaction, headache, insomnia, malaise, paresthesia, peripheral neuritis (poly)
Neuromuscular & skeletal: Accelerated bone maturation, gout
Ophthalmic: Blurred vision, cataract (transient), diplopia, lacrimation, scotoma (ring), subconjunctival hemorrhage
Renal: Decreased creatinine clearance, nephrotic syndrome (reversible)
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Chest pain, pericardial effusion (Avatapalle 2012)
Dermatologic: Hypertrichosis (Salido 2013)
Gastrointestinal: Necrotizing enterocolitis
Hematologic & oncologic: Hemolysis (Best 1975), immune thrombocytopenia (Thus 2019), thrombocytopenia (Adachi 2014)
Respiratory: Pulmonary hypertension (infants and neonates) (Ohnishi 2020)
Hypersensitivity to diazoxide, other thiazides, or any component of the formulation; functional hypoglycemia
Concerns related to adverse effects:
• Abnormal facial features: Development of abnormal facial features was reported in children treated >4 years for hypoglycemia hyperinsulinism.
• Hyperglycemic crises: Ketoacidosis or hyperosmolar coma may occur during treatment; usually in patients with concomitant illness; prompt recognition and treatment are essential.
Disease-related concerns:
• Heart failure: Use may lead to increased fluid retention due to antidiuretic properties and may precipitate heart failure in patients with compromised cardiac reserve.
• Gout: Use with caution in patients with hyperuricemia or a history of gout.
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Pediatric: May displace bilirubin from albumin; use caution in newborns with hyperbilirubinemia. Pulmonary hypertension has been reported in newborns and young infants and was reversible upon drug discontinuation; monitor patients (especially patients with risk factors for pulmonary hypertension) for respiratory distress and discontinue diazoxide if pulmonary hypertension is suspected.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).
Initiate treatment with diazoxide under close clinical supervision; carefully monitor blood glucose and clinical response until patient's condition becomes stable (usually several days). Regular monitoring of urine for glucose and ketones (especially under conditions of stress) are required with prolonged therapy; abnormal results should be reported to physician promptly. Periodic monitoring of blood glucose is required for dosage adjustment.
Pulmonary hypertension has been reported in newborns and infants receiving diazoxide for hypoglycemia; since the early 1970’s, eleven cases have been reported either to the FDA or within the literature; in the majority of cases, the neonate/infant had other ongoing serious medical conditions and were at high risk for development of pulmonary hypertension; reported onset was within a day to a few months after diazoxide therapy initiation and in all cases, the pulmonary hypertension resolved or improved with discontinuation of the diazoxide. Pulmonary hypertension may be dose dependent; a review of published cases reported that circulatory effects were observed most frequently at doses ≥10 mg/kg/day. Monitor neonates and infants closely for signs of respiratory distress (tachypnea, flaring nostrils, grunting, chest wall retractions), cyanosis, or feeding intolerance, particularly those neonates and infants with risk factors for pulmonary hypertension (eg, meconium aspiration syndrome, respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, sepsis, congenital diaphragmatic hernia, congenital heart disease); discontinue if pulmonary hypertension is identified (FDA 2015; Timlin 2017).
Transient cataracts have been reported in an infant in association with hyperosmolar coma; cataracts subsided following correction of hyperosmolarity. Abnormal facial features have been reported in 4 children who received diazoxide for >4 years for the treatment of hypoglycemia hyperinsulinism.
The oral suspension contains 7.25% alcohol. Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension, Oral:
Proglycem: 50 mg/mL (30 mL) [chocolate mint flavor]
Generic: 50 mg/mL (30 mL)
Yes
Suspension (Diazoxide Oral)
50 mg/mL (per mL): $12.38 - $12.40
Suspension (Proglycem Oral)
50 mg/mL (per mL): $16.26
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Proglycem: 100 mg
Oral: Shake suspension well before each use; suspension comes with calibrated dropper (to deliver dose of 10 to 50 mg, in 10 mg increments).
Shake suspension well before each use.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light. Store in carton until contents are used.
Management of hypoglycemia related to hyperinsulinism secondary to the following conditions: Islet cell adenoma, adenomatosis, or hyperplasia; extrapancreatic malignancy; nesidioblastosis; leucine sensitivity (All indications: FDA approved in neonates, infants, and children)
Management of hypoglycemia related to hyperinsulinism secondary to the following conditions: Inoperable islet cell adenoma or carcinoma; extrapancreatic malignancy (FDA approved in adults)
Diazoxide may be confused with diazePAM, Dyazide
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: Diazoxide may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: Diazoxide may decrease the serum concentration of Fosphenytoin-Phenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the adverse/toxic effect of Diazoxide. Risk C: Monitor therapy
Thiopental: May enhance the hypotensive effect of Diazoxide. Risk C: Monitor therapy
Diazoxide crosses the human placenta and appears in cord blood. Altered carbohydrate metabolism, hyperbilirubinemia, and thrombocytopenia have been reported in the fetus or neonate. Alopecia and hypertrichosis lanuginosa have also been reported in infants following maternal use of diazoxide during the last 19 to 60 days of pregnancy.
Blood glucose, serum uric acid, electrolytes, renal function (BUN, SCr); AST, CBC with differential, platelets; urine glucose and ketones (baseline and frequently during therapy initiation and then periodically); blood pressure (especially with IV therapy), heart rate; signs of pulmonary hypertension (neonates/infants [eg, respiratory, cyanosis, feeding intolerance]); consider echocardiogram in neonates and infants (baseline, after initiation [5 days of therapy], and periodically) (Timlin 2017)
Opens ATP-dependent potassium channels on pancreatic beta cells in the presence of ATP and Mg2+, resulting in hyperpolarization of the cell and inhibition of insulin release. Diazoxide binds to a different site on the potassium channel than the sulfonylureas (Doyle, 2003).
Onset of action: Hyperglycemic: Oral: Within 1 hour
Duration: Hyperglycemic: Oral: Normal renal function: ≤8 hours
Protein binding: >90%
Half-life elimination: Oral: Children: 9.5 to 24 hours; Adults: 24 to 36 hours
Excretion: Urine (50% as unchanged drug)
Altered kidney function: Plasma half-life is prolonged.
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