Diazoxide works by blocking the release of insulin from the pancreas, thus allowing recovery from hypoglycemia in, most commonly, pediatric patients with congenital hyperinsulinemic hypoglycemia. This is a medication that is not likely to be required often, but is effective when it is called upon.
Of note, there was recently an FDA-issued warning in September 2015 regarding findings of pulmonary hypertension and respiratory distress in infants and children (especially those with other factors that may contribute to either of these). This has been found to be reversible upon discontinuation of diazoxide.
Regarding cost, one bottle contains multiple doses, as each 30mL bottle contains 1500mg of diazoxide. Depending on the age and weight of the child, a bottle would likely contain 15-30 days’ worth of medication. The question that next needs to be answered is regarding the number of days of therapy.
This is addressed in the article, “Management strategies for neonatal hypoglycemia,” published in The Journal of Pediatric Pharmacology and Therpeutics in 2013. According to the authors, the typical time it takes for these patients to see normal blood glucose levels is roughly 2-4 days, but a trial of 5-8 days is recommended before stopping the dose.2 That being said, and per the above cost calculations, consider a patient who is one year old and weighs 11kg, and the plan is to trial diazoxide for a full eight days. The total cost would be approximately $140, and the total dose over those eight days would be 17.6mL (just over half of one bottle). Overall, diazoxide has been considered a first-line agent for congenital hyperinsulinemic hypoglycemia, and has been found to be especially effective for the treatment of this disorder in infants.
Generic (Trade) Name: | diazoxide (Proglycem) |
Drug Class: | hyperglycemic agent |
Formulation: | oral suspension (for pediatric population) |
FDA-Approved Indications: | hypoglycemia, due to (usually congenital) hyperinsulinism |
Off-Label Usage: | none at this time |
Mechanism of Action: | increase in blood glucose via inhibition of insulin release from pancreas via opening of the β-cell KATP channels2 |
Adverse Drug Reactions
- sodium and fluid retention (esp. young infants and adults)
- hirsutism
- pulmonary hypertension/respiratory distress (neonates, infants, children)
- GI intolerance
- hyperglycemia/glycosuria, diabetic ketoacidosis
- hyperosmolar non-ketoacidotic coma
- rarely: hypotension, eosinophilia, decreased hemoglobin/hematocrit, increased liver enzymes, decreased CrCl, decreased urinary output, anxiety, dizziness, insomnia, pruritis, extrapyramidal signs, blurred vision, diplopia, lacrimation, fever, lymphadenopathy, gout, thrombocytopenia
Monitoring
- blood glucose
- serum electrolytes and uric acid
- BUN, SCr, CrCl
- CBC with differential
- LFTs, especially bilirubin
- urine glucose and ketones
- respiratory distress (especially in neonates and infants)
Contraindications/Warnings
Contraindications
- functional hypoglycemia (also called reactive hypoglycemia – low blood sugar in the four hours after eating, often accompanied by shakiness, sleepiness, lightheadedness, hunger)
- hypersensitivity to diazoxide or other thiazide
Precautions
- treatment under close monitoring only with regular assessment of clinical response
- prolonged use requires increased monitoring for glucosuria and ketones in the urine
- take care when administering concomitantly with other medications that also have antihypertensive effects
- may displace bilirubin from albumin (keep in mind if treating newborn with bilirubinemia)
Drug Interactions
- diuretics – potentiation of hyperglycemic and hyperuricemic effects
- warfarin – potentiation of hypoprothrombin effects
- diphenylhydantoin – may lead to loss of seizure control
- chlorpromazine – may enhance hyperglycemic action of diazoxide
How supplied, preparation, administration, and stability/storage
How supplied:
- 50mg/mL suspension
- 30 mL bottle
Dosing
- adults, children, adolescents 3 mg/kg/day divided into every 8 hour dosing
usual range: 3-8 mg/kg/day divided into every 8 or 12 hour dosing - neonates and infants 10 mg/kg/day divided every 8 hours
usual range: 8-12 mg/kg/day divided into every 8 or 12 hour dosing
*range of 5-20 mg/kg/day divided every 8 hours has been used
Administration
- shake suspension well prior to administration
Stability/Storage
- store at room temperature- 25 °C (77°F)
- may have “excursions” between 15°C and 30°C (59°F and 86°F)
- store in box until use and protect from light
Pharmacokinetics and Pharmacodynamics
- onset of action = 1 hour
- duration = 8 hours (normal renal function)
- >90% bound to serum proteins, renal excretion
- half-life = pediatrics 9-24 hours
adults 24-36 hours
- per package insert, if no effect is seen within 2-3 weeks, diazoxide should be discontinued
Hazardous/Cytotoxic
Animal studies were inconclusive regarding risks, primarily risks that were found were related to the embryonic stage of development
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