DIAZOXIDE

Diazoxide DBL

Reviewed by Dr Mariam Buksh, Karen Anderson-Hawke (NS-ANP), and Helen Lamb (NS-ANP)
November 2007
Administration Newborn Drug Protocol Index Newborn Services Home Page

Dose and Administration

  1. For hypogylcaemia 1-5
    1. Recommended initial dose is 5-10mg/kg/day in 2-3 doses
    2. For hypoglycaemia secondary to hyperinsulinaemia, up to 10-15mg/kg/day in 8-12 hourly doses
  2. For severe hypertension 4
    1. 1-3mg/kg for severe hypertension.  Can be given every 5-15 minutes.  Dose is titrated according to blood pressure response
  3. 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

  1. Compensatory hypertension with aortic coarctation or AV shunt.
  2. Caution in infants with congestive heart failure.
  3. 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 diuretics 4. 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 Effects

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