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Drug dosage identifier

Diazoxide

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Note: This is a Section 29 Drug when administered by oral preparation. This means that a record must be kept of babies to whom it has been administered, and parents should be informed that it is not registered for oral use in NZ.

Dose and administration

For hypogylcaemia 1-5

  • Recommended initial dose is 5-10mg/kg/day in 2-3 doses
  • For hypoglycaemia secondary to hyperinsulinaemia, up to 10-15mg/kg/day in 8-12 hourly doses

For severe hypertension 4

  • 1-3mg/kg for severe hypertension. Can be given every 5-15 minutes. Dose is titrated according to blood pressure response

Concurrent administration of a diuretic (e.g. hydrochlorathiazide) is recommended. 2,6

Indications

  1. Hypoglycaemia (due to hyperinsulinaemia)
  2. Hypertensive crisis (not the drug of choice in neonates)

Contraindications and precautions

  • Compensatory hypertension with aortic coarctation or AV shunt.
  • Caution in infants with congestive heart failure.
  • Caution in infants with renal insufficiency and impaired carbohydrate metabolism.

Clinical pharmacology

Diazoxide is a nondiuretic hypotensive and anithypoglycaemic agent that is structurally related to the thiazide diuretics4. It reduces peripheral vascular resistance and blood pressure as a result of direct vasodilatory effect on smooth muscle in peripheral arterioles. Diazoxide causes sodium and water retention and decreased urinary output, which can result in expansion of plasma and extracellular fluid volume, oedema and congestive cardiac failure.

Diazoxide increases blood glucose concentration by inhibiting pancreatic insulin secretion, stimulating the release of catecholamines and/or increasing the hepatic release of glucose. Diazoxide has a marked inhibitory effect on glucose induced insulin secretion.  After oral administration of diazoxide suspension, the hyperglycaemic effects begin within 1 hour and last approximately 8 hours in patients with normal renal function.1,4

Diazoxide crosses the placenta and brain barrier. Animal studies have shown adverse effects of diazoxide on fetal development, presumed to be secondary to altered glucose metabolism.4  Excretion in breast milk is not known. Use during lactation has not been studied.  Use with extreme caution.

The effect of diazoxide after an IV bolus is usually maximal within 5 minutes and will persist up to 24 hours. Vd is 0.18L/kg. Elimination is mainly hepatic (80%) and 20% renal. Elimination half life is 15-30 hours.  Approximately 90% of diazoxide in the blood is bound to plasma proteins. 4  Elimination half life following a single oral or IV dose has reportedly ranged from 21-45 hours in adults with normal renal function, limited data suggests that the terminal elimination half life may be shorter in children.1

Possible adverse effect

  1. Sodium and water retention, oedema.
  2. Hyperglycaemia.
  3. Hypotension.
  4. Hypertrichosis.
  5. Neonatal jaundice (displaces protein-bound fraction).
  6. Gastrointestinal disturbances (nausea and vomiting).
  7. Arrhythmias, tachycardia.
  8. Cerebral ischemia/convulsions.
  9. Blood dyscrasias (neutropenia, leukopenia, and thrombocytopenia).
  10. Transient cataracts with prolonged use.

Special considerations

  1. Is NOT a drug of choice in treatment of hypertensive emergencies in newborns.
  2. Extravasation can cause severe inflammatory reaction.
  3. Hypokalaemia potentiates the hyperglycaemic effect.
  4. Diazoxide causes sodium retention and diuretics may need to be administered concomitantly.  Doses of >20mg/kg/day often result in fluid retention precipitating congestive heart failure.
  5. Concomitant administration with diuretics, anti-hypertensives, and corticosteroids potentiates hyperglycaemia and hypotension.  Concomitant administration with phenytoin has resulted in both failure to achieve seizure control and phenytoin toxicity 4.

ANTIDOTE: discontinue diazoxide; administer insulin as necessary for hyperglycaemia; treat hypotension with sympathomimetic agents.

Management of Diazoxide administration

Description

IV preparation

  • Clear colourless solution 15 mg/ml in 20 ml ampoules.
  • pH adjusted to 11.5 by sodium hydroxide.
  • For IV use only.

Oral preparation

Proglycem 50mg/ml

Prescription

  • Individual doses are charted on the stat pages of the drug prescription chart in mg/dose.
  • Maintenance doses are charted on the prescription chart in mg/dose.

Administration

IV Injection

  • Administered only intravenously. Do NOT administer IM or SC.
  • Administered by a doctor/NS-ANP, or a nurse with Neonatal IV Drug Certification.
  • Do NOT further dilute.
  • Filter prior to administration through a Pall 0.2 micron filter.
  • Administer by IV injection over 30 seconds.
  • No compatibility data available.
  • Do NOT mix with other drugs, IV solutions, blood or blood products.
  • Use a separate line for diazoxide.

Oral

Administer with food.

Nursing considerations

  • Observe site closely during administration for extravasation. May cause severe inflammatory reaction.
  • Observe for signs of adverse effects.
  • Monitor glucose levels carefully.
  • Monitor blood pressure (preferably continuously).
  • Continuous cardiorespiratory monitoring. Observe for arrhythmias.
  • Monitor fluid balance carefully.
  • Weigh daily.
  • Nurse flat during infusion and for 1 hour after infusion.

Storage

IV Preparation

  • Unopened store in a cool place <25ºC. Do NOT freeze.
  • Protect from light, heat and freezing. Darkened solutions have decreased potency. Do NOT use.
  • Discard after use.

Oral Preparation

  • Store in a cool place <25°. Do not freeze.
  • Protect from light.

References

  1. Alexander, S, Anazodo, A and Hussain, K. Interactions of diazoxide with frusemide, spironolactone, and acetylsalicylic acid in a patient with hyperinsulism of infancy and Fallot tetralogy. Eur J Pediatr. 162: 806-807.
  2. Aynsley-Green A, Hussain K, Hall J, Saudubray JM, Nihoul-Fekete C, De Lonlay-Debeney P, Brunelle F, Otonkoski T, Thornton P and Lindley KJ. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal Ed 2000; 82: F98-F107
  3. De Lonlay P, Touati G, Robert Jaen-Jacques and Saudubray J-M. Persistent hyperinsulinaemic hypoglycaemia. Semin Neonatol 2002; 7: 95-100
  4. Diazoxide: AHFS Detalied Monogrpah. Medscape.
    http://www.medscape.com/druginfo/monograph?
    cid=med&drugid=10322&drugname=Diazoxide+IV&monotype=monograph. Accessed on 30/07/2007.
  5. McGowan JE. Neonatal Hypoglycemia. Neoreviews. July 1999; e6-e15.
  6. Lindley KJ, Dunne MJ. Contemporary strategies in the diagnosis and management of neonatal hyperinsulinaemic hypoglycaemia. Early Human Development. 2005; 81: 61-72.

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Document Control

  • Date last published: 31 August 2018
  • Document type: Clinical Guideline
  • Services responsible: ADHB Pharmacy, Neonatology
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years