Disclaimer to the On-line Edition
This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.



  • to decrease the incidence and severity of neonatal apnea


  • caffeine is a methylxanthine type of drug (like theophylline)
  • a potent CNS stimulant
  • stimulates central respiratory centre in medulla and increases the sensitivity to carbon dioxide
  • increases cardiac contractility and may produce tachycardia
  • increases renal blood flow and GFR
  • largely excreted unchanged in the urine of neonates; metabolism similar to that in adults begins to occur at about 3 - 4 months of age
  • 3 mechanisms of action have been proposed: translocation of intracellular calcium, increase in cyclic 3'5' AMP, and inhibition of adenosine effects; the latter is possibly the most important
  • in premature infants, 3 to 32 days old, the following parameters were reported:
    • mean volume of distribution (Vd) = 0.9 L/kg (range 0.5 to 1.3 L/kg)
    • mean serum half life (t1/2) = 100h (range 40 to 230h)
    • mean total body clearance (TBC) = 9 mL/kg/h (range 2.5 to 17mL/kg/h)
  • therapeutic serum concentration is 25 to 80 micromol/L
  • because of the extended half life, a blood sample for therapeutic drug monitoring may be taken at any time during the 24 hour dosage interval

Side Effects

  • caffeine has a wide therapeutic index, i.e. the serum levels which result in side effects are generally much higher than the therapeutic range
  • side effects which have been reported to occur at serum concentrations greater than the therapeutic range include transient jitteriness and tachycardia (if these side effects occur and are persistent, withdraw caffeine therapy to determine if it is responsible).
  • in 3 term infants, who received 36 to 136 mg/kg/day, acute toxicity manifested as tachypnea, fine tremor of the extremities, opisthotonus (a form of spasm in which the head and heels are bent backward and the body bowed forward), tonic - clonic movements and nonpurposeful jaw and lip movements.


  • caffeine citrate is very acidic (ph 3 to 4); therefore DO NOT GIVE IM
  • if heart rate is greater than 18O beats/min, consult with physicians before administering dose



10 mg/kg of caffeine base - slow IV infusion over 30 minutes or po

(first dose to be given 24 hours after the loading dose)

2.5 mg/kg of caffeine base q24h

  • slow IV infusion over 30 minutes or po (IV push results in noticeable vein irritation)
  • reassess dosage weekly taking into account weight increase of the infant; (the 7 doses until reassessment includes the loading dose)


  • caffeine (base) 10mg/ml, present as caffeine citrate in:
    1. syringes for IV use
    2. single use vials for IV use
    3. bottles for oral use
  • these are all extemporaneous products which are specially prepared by the Department of Pharmacy


  1. Aranda J V, Gondin D and Sasyniuk B I. Pharmacologic considerations in the therapy of neonatal apnea. Pediatric Clinics of North America, 1981; 28, 113-133.
  2. Aranda J V, Cook C E, Gorman W et al. Pharmacokinetic profile of caffeine in the premature newborn infant with apnea. The Journal of Pediatrics,1979; 94, 663-668.
  3. Roberts, RJ: Drug Therapy in Infants, W.B. Saunders, Toronto, 1984.

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