Caffeine

Caffeine

Indication

• To decrease the incidence and severity of neonatal apnea

Pharmacology

• 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

Precautions

• 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

Dose

• 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)
• Compatible with TPN and LIPID

Available

• 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