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Doxapram

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Dose and administration

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Continuous Intravenous Infusion

  • Start at 0.5mg/kg/hour and, if necessary, titrate upwards at increments of 0.5 mg/kg/hour to a usual maximum of 1.5 mg/kg/hour
  • Review continuing use on a daily basis. There is some evidence that the effect may not be sustained.

Indications

Apnoea of prematurity unresponsive to caffeine citrate (or aminophylline).

Contraindications and precautions 

Precautions

Impaired renal or hepatic function

Clinical pharmacology

Doxapram is a respiratory stimulant, acting principally through the central respiratory centres in the medulla. Stimulation of peripheral carotid chemoreceptors may also contribute to the respiratory action. The resultant effect is an increase in tidal volume with an increase in respiratory rate. Doxapram has a quick onset and short duration of action. A release in catecholamines has been noted following the use of doxapram, leading to a pressor effect, attributed to an increase in cardiac output rather than a peripheral vasoconstriction.

Doxapram undergoes extensive hepatic metabolism, with very little free drug appearing in the urine.

Possible adverse effects

  • Hypertension is the most common adverse effect seen in preterm infants, and can even occur at low doses7. Monitor blood pressure regularly.
  • QTc prolongation, 2nd degree heart block, arrhythmias.
  • Seizures (may be associated with high doses), irritability, flushing, sweating, involuntary movements, muscle spasm.
  • Respiratory distress
  • Vomiting, diarrhoea, urinary retention.
  • Extravasation may cause thrombophlebitis or skin irritation.

Drug interactions

Special considerations

  • Do not use in conjunction with mechanical ventilation.
  • Monitor:
    B.P. and pulse rate (sudden onset of hypotension or dyspnoea suggests that doxapram should be stopped)
    Blood gases: consider ventilation if there is a deterioration in blood gas parameters without clinical improvement
  • Watch for accumulation if high doses are infused for more than 36 to 48 hours.
  • Signs of overdose are: excessive pressor effect, tachycardia, skeletal muscle hyperactivity (tremors), enhanced deep tendon reflexes.
  • Some preparations of doxapram contain benzyl alcohol as a preservative (e.g.Wyeth brand of Dopram®). Benzyl alcohol may cause significant metabolic and neurological disturbance in infants.
  • Doxapram is not licensed for use in children. There are limited trials evaluating its use in neonates for the treatment of apnoea.

Management of Doxapram administration

Description

  • Doxapram hydrochloride 20mg/ml. pH 3.5 - 5
  • Dopram® (Anpharm): Doxapram 20mg/ml (Anpharm brand does not contain preservative)

This brand is not licensed in N.Z. (2011) and therefore only available under Section 29 of the Medicines Act. Prescription

Prescription

  • Dilute to 1 - 2 mg/ml for administration5
  • Maximum concentration for administration is 2mg/ml8,9
  • Charted on the medication chart as a continuous infusion giving the amount of doxapram to be added and the base fluid type and volume, specifying the dose in mg/kg/hour and the equivalent ml/hour rate
  • Charted on the fluid chart as ml/hour and mg/kg/hour

Administration

  • Compatible with glucose 5%, glucose 10%, sodium chloride 0.9%.
  • Incompatible with parenteral nutrition, alkaline solutions (e.g. sodium bicarbonate , and frusemide so run separately).
  • Administer as a continuous infusion via a syringe pump
  • Change preparation every 24 hours

Nursing considerations

  • Babies on doxapram will usually also be receiving CPAP and need meticulous care in its application.
  • Capillary or arterial blood gases as ordered.
  • Monitor vital signs (BP, pulse rate, saturations).

Storage

  • Store at room temperature below 25°C. Do not refrigerate.
  • Vials and amps are single use only.

Selected references

  1. Sweetman S. (Ed.) Martindale: The Extra Pharmacopoeia. (33rd. ed). London : Royal Pharmaceutical Society; 2002.
  2. Dopram® (data sheet online). Wyeth-Ayerst Laboratories (Date of preparation 22 June 1999). Available from http.//www.medsafe.govt.nz/profs.htm
  3. Doxapram, Hutchison TA, Shahan DR (eds): Drugdex ® system. Micromedex ® Inc., Greenwood Village, Colorado. (Edition expires 12/2003).
  4. Medicines for Children. Royal College of Paediatrics and Child Health. London: RCPCH Publications Limited, 1999
  5. Martin, J, Managing editor. BNF for children 2010-2011. London: BMJ Group, Pharmaceutical Press & RCPCH Publications Ltd; 2010.
  6. Barrington KJ, Finer NN, Torok-Both G, Jamali F, Coutts RT. Dose-response relationship of doxapram in the therapy for the refractory idiopathic apnea of prematurity. Pediatrics. 1987; 80 (1):22-27.
  7. Huon C, Rey E, Mussat P, Moriette G. Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study. Acta Paediatr. 1998; 87:1180-4.
  8. Phelps SJ, Hak EB, Crill CM, editors. Teddy bear book: Pediatric injectable drugs. 8th ed. Bethesda, MD: American Society of Heath-System Pharmacists; 2007.
  9. Trissel LA. Handbook on Injectable Drugs. American Society of Health-System Pharmacists (ASHP) 16th Edition.

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Document Control

  • Date last published: 30 November 2011
  • Document type: Drug Dosage Guideline
  • Services responsible: ADHB Pharmacy, Neonatology
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years