Mechanism of effect
Increases levels of 3'5' cyclic AMP by inhibiting phosphodiesterase; CNS stimulant which increases medullary respiratory center sensitivity to carbon dioxide, stimulates central inspiratory drive, and improves skeletal muscle contraction (diaphragmatic contractility); prevention of apnea may occur by competitive inhibition of adenosine
- Central Nervous System Stimulant
- Phosphodiesterase Enzyme Inhibitor, Nonselective
Vd: Neonates: 0.8 to 0.9 L/kg;
Adults: 0.6 L/kg.
Hepatic, via demethylation by CYP1A2.
Note: In neonates, interconversion between caffeine and theophylline has been reported (caffeine levels are ~25% of measured theophylline after theophylline administration and ~3% to 8% of caffeine would be expected to be converted to theophylline)
Neonates: Urine (86% unchanged).
Infants ≥9 months, Children, Adolescents, and Adults: Urine (1% unchanged).
Time to Peak
Serum: Preterm neonates: Oral: 30 minutes to 2 hours.
Neonates: 72 to 96 hours.
Infants ≥9 months, Children, Adolescents, and Adults: 5 hours.
Use: Labeled Indications
Caffeine citrate: Treatment of idiopathic apnea of prematurity
Caffeine and sodium benzoate: See Off-Label uses.
Caffeine [OTC labeling]: Restore mental alertness or wakefulness when experiencing fatigue
Usual Pediatric Dose for Apnea of Prematurity
28 Weeks to Less Than 33 Weeks Gestational Age:
-Loading Dose: 20 mg/kg IV over 30 minutes one time.
-Maintenance Dose: 5 mg/kg orally or IV over 10 minutes every 24 hours.
-Treatment Duration: Safety and efficacy of this drug for treatment of apnea of prematurity have not been established beyond 12 days.
Use: Short-term treatment of apnea of prematurity in infants.
Renal Dose Adjustments
Caffeine Citrate: Use with caution in infants with impaired renal function; monitor serum drug concentrations and adjust dose accordingly to avoid toxicity.
Liver Dose Adjustments
Caffeine Citrate: Use with caution in infants with impaired hepatic function; monitor serum drug concentrations and adjust dose accordingly to avoid toxicity.
Safety and efficacy of caffeine citrate for treatment of apnea of prematurity have only been established in pediatric patients 28 weeks to less than 33 weeks gestational age.
Consult WARNINGS section for additional precautions.
Caffeine Citrate: Data not available.
Hypersensitivity to caffeine or any component of the formulation; sodium benzoate is not for use in neonates
Side effects requiring immediate medical attention
Along with its needed effects, caffeine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking caffeine:
black, tarry stools
blood in the stools or urine
burning feeling or tenderness in the stomach
coughing or vomiting blood
decreased urine output
rapid, shallow breathing
rapid weight gain
severe stomach pain
swelling of the face, ankles, or hands
unusual tiredness or weakness
vomiting of blood or material that looks like coffee grounds
Get emergency help immediately if any of the following symptoms of overdose occur while taking caffeine:
Symptoms of overdose
• Anxiety: Avoid use in patients with anxiety, agitation, or tremor.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; avoid use in patients with symptomatic cardiac arrhythmias.
• Gastrointestinal disease: Use with caution in patients with a history of peptic ulcer and/or gastroesophageal reflux.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; may lower seizure threshold leading to new onset or breakthrough seizure activity.
Dosage form specific issues:
• OTC products: OTC products contain 200 mg of caffeine per tablet approximately the amount of caffeine similar to one cup of coffee; limit the use of other caffeine-containing beverages or foods.
• Product interchangeability: Caffeine citrate should not be interchanged with caffeine and sodium benzoate.
Other warnings and precautions:
• Transcutaneous electrical nerve stimulation: Analgesia from transcutaneous electrical nerve stimulation may be lessened with concomitant caffeine use (Marchand 1995).
Points of recommendation
May be administered without regard to feedings or meals. May administer injectable formulation (caffeine citrate) orally.
AU TGA pregnancy category: A
US FDA pregnancy category: C
Breast feeding warning
Caffeine appears in breastmilk rapidly after maternal ingestion as it readily crosses the placenta into the fetal circulation. Fussiness, jitteriness and poor sleep patterns have been reported in the infants of mothers with very high caffeine intakes (equivalent to about 10 or more cups of coffee per day). Studies in mothers taking 5 cups of coffee per day found no stimulatory effects in infants 3 weeks of age or older. Preterm and younger newborn infants metabolize caffeine very slowly and therefore a lower maternal intake is preferable. Coffee intake of more than 450 mL daily may decrease breastmilk iron concentrations and result in mild iron deficiency anemia in some breastfed infants.
Caution is recommended
Excreted into human milk: Yes
Caffeine group drugs