Diazoxide

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suspension, Oral:

Proglycem: 50 mg/mL (30 mL) [chocolate mint flavor]

Pharmacology

Mechanism of Action

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).

Pharmacokinetics/Pharmacodynamics

Excretion

Urine (50% as unchanged drug)

Onset of Action

Hyperglycemic: Oral: Within 1 hour

Duration of Action

Hyperglycemic: Oral: Normal renal function: ≤8 hours

Half-Life Elimination

Oral: Children: 9.5 to 24 hours; Adults: 24 to 36 hours

Protein Binding

>90%

Use in Specific Populations

Special Populations: Renal Function Impairment

Plasma half-life is prolonged.

Use: Labeled Indications

Hyperinsulinemic hypoglycemia: Management of hypoglycemia due to hyperinsulinism due to the following conditions in adults (ie, inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy) and infants and children (ie, leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis; may be used preoperatively as a temporary measure, and postoperatively, if hypoglycemia persists).

Note: Consider treatment with diazoxide when other specific medical therapy or surgical management for hypoglycemia due to the above conditions either has been unsuccessful or is not feasible.

Contraindications

Hypersensitivity to diazoxide, other thiazides, or any component of the formulation; functional hypoglycemia

Dosage and Administration

Dosing: Adult

Hyperinsulinemic hypoglycemia: Oral: Initial dose: 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: In certain instances, patients with refractory hypoglycemia may require higher doses. Discontinue if no effect after 2 to 3 weeks.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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).

Administration

Shake suspension well before each use.

Storage

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.

Drug Interactions

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Blood Pressure Lowering Agents: Diazoxide may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Fosphenytoin: Diazoxide may decrease the serum concentration of Fosphenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations. Monitor therapy

Phenytoin: Diazoxide may decrease the serum concentration of Phenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the adverse/toxic effect of Diazoxide. Monitor therapy

Thiopental: May enhance the hypotensive effect of Diazoxide. Monitor therapy

Test Interactions

Serum renin concentrations and IgG concentrations may be increased. Serum cortisol concentrations may be decreased. May cause a false-negative insulin response to glucagon.

Adverse Reactions

Frequency not defined.

Cardiovascular: Cardiac failure (due to sodium and water retention), hyperosmolar coma (nonketotic), hypertension (transient), hypotension, palpitations, tachycardia

Central nervous system: Anxiety, dizziness, extrapyramidal reaction, headache, insomnia, malaise, paresthesia, peripheral neuritis (poly)

Dermatologic: Cutaneous candidiasis, loss of scalp hair, pruritus, purpura, skin rash

Endocrine & metabolic: Albuminuria, diabetic ketoacidosis, fluid retention, galactorrhea, glycosuria, gout, hirsutism, hyperglycemia, sodium retention

Gastrointestinal: Abdominal pain, acute pancreatitis, ageusia (transient), anorexia, diarrhea, intestinal obstruction, nausea, pancreatic necrosis, vomiting

Genitourinary: Azotemia, decreased urine output, hematuria, lump in breast (enlargement), nephrotic syndrome (reversible), uricosuria

Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, decreased serum immunoglobulins (IgG), eosinophilia, hemorrhage (excessive), lymphadenopathy, neutropenia (transient), thrombocytopenia

Hepatic: Increased serum alkaline phosphatase, increased serum AST

Infection: Herpes virus infection

Neuromuscular & skeletal: Accelerated bone maturation, craniofacial abnormality (children with chronic use), weakness

Ophthalmic: Blurred vision, cataract (transient), diplopia, lacrimation, scotoma (ring), subconjunctival hemorrhage

Renal: Decreased creatinine clearance

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Chest pain, pulmonary hypertension (infants and neonates)

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal facial features: Development of abnormal facial features was reported in children treated >4 years for hypoglycemia hyperinsulinism.
• Hyperosmolar coma: Nonketotic hyperosmolar coma may occur during treatment; usually in patients with concomitant illness; prompt recognition and treatment are essential. Transient cataracts have been reported which subside following correction of hyperosmolarity.
• Ketoacidosis: Ketoacidosis may occur during treatment, usually in patients with concomitant illness.

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; a reduced dose should be considered.

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).

Monitoring Parameters

Clinical response, blood glucose, serum uric acid, BUN, creatinine clearance, CBC with differential, AST; urine glucose and ketones (especially under stress conditions and during prolonged treatment); serum electrolytes and uric acid; respiratory distress (neonates and infants [especially those with risk factors for pulmonary hypertension]).

Pregnancy

Pregnancy Considerations

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.

Patient Education

What is this drug used for?

• It is used to treat low blood sugar.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Lack of appetite
• Diarrhea
• Change in taste
• Loss of strength and energy

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting
• Blue/gray skin discoloration (children)
• Fast breathing (children)
• Flaring of nostrils (children)
• Grunting (children)
• Abnormal chest movements (children)
• Trouble eating (children)
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Severe constipation
• Severe abdominal pain
• Fast heartbeat
• Abnormal heartbeat
• Bruising
• Bleeding
• Severe dizziness
• Passing out
• Severe headache
• Chest pain
• Unable to pass urine
• Change in amount of urine passed
• Vision changes
• Tremors
• Trouble moving
• Hair growth on forehead, back, arms, and legs
• Stiffness
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.