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Methylxanthine (Apnoea of Prematurity) Pregnancy: Not applicable to the treated population — this is a neonatal medicine. The SPC records that caffeine at high doses was embryotoxic and teratogenic in animal studies, but states these effects are not relevant to short-term administration in the preterm infant population, and that effects on reproductive performance observed in animals are not relevant to its indication in preterm newborn infants. Breast-feeding: caffeine is excreted into breast milk and readily crosses the placenta into the foetal circulation; breast-feeding mothers of newborn infants treated with caffeine citrate should not ingest caffeine-containing foods, beverages or medicinal products containing caffeine, and baseline plasma caffeine concentrations should be measured in newborns whose mothers consumed large quantities of caffeine prior to delivery.

Caffeine Citrate

Brand names: Peyona

Caffeine citrate is a methylxanthine central nervous system stimulant used to treat apnoea of prematurity in neonates.

Adult dose

Dose: Not applicable — no adult dose is given in the SPC. This product's posology is stated only for the treatment of apnoea of prematurity in preterm newborn infants; the full regimen is in the paediatric dose below
Route: Not applicable — the SPC states routes (intravenous infusion by syringe infusion pump or other metered infusion device, or oral administration such as through a nasogastric tube) only for the preterm newborn regimen
Frequency: Not applicable — see the paediatric (neonatal) dose
Max: Not applicable — no adult maximum is stated because no adult indication exists in this SPC
NO ADULT DOSE IS PUBLISHED, and none is expected: this is a neonatal page. §4.2 states that treatment should be initiated under the supervision of a physician experienced in neonatal intensive care and administered only in a neonatal intensive care unit with adequate facilities for patient surveillance and monitoring.

Paediatric dose

Dose: 20 mg/kg
Route: Loading dose: slow intravenous infusion over 30 minutes, using a syringe infusion pump or other metered infusion device. Maintenance dose: slow intravenous infusion over 10 minutes by the same means, or oral administration such as through a nasogastric tube. The product must NOT be given by intramuscular, subcutaneous, intrathecal or intraperitoneal injection
Frequency: Loading dose: once. Maintenance: 5 mg/kg every 24 hours, beginning 24 hours after the loading dose
Max: No absolute (weight-independent) maximum is stated. In preterm newborn infants with insufficient clinical response to the recommended loading dose, a second loading dose of 10-20 mg/kg maximum may be given after 24 hours; higher maintenance doses of 10 mg/kg body weight could be considered in case of insufficient response, taking into account the potential for accumulation of caffeine due to its long half-life in preterm newborn infants
Concentration: 20 mg/ml
THE 20 mg/kg FIGURE IS THE ONE-TIME LOADING DOSE — THE MAINTENANCE DOSE IS FOUR TIMES SMALLER (5 mg/kg every 24 hours). §4.2 verbatim: 'The recommended dose regimen in previously untreated infants is a loading dose of 20 mg caffeine citrate per kg body weight administered by slow intravenous infusion over 30 minutes, using a syringe infusion pump or other metered infusion device. After an interval of 24 hours, maintenance doses of 5 mg per kg body weight may be administered by slow intravenous infusion over 10 minutes every 24 hours. Alternatively, maintenance doses of 5 mg per kg body weight may be administered by oral administration, such as through a nasogastric tube every 24 hours.' The SPC's own dose table gives the loading dose as 1.0 mL/kg body weight = 20 mg/kg IV over 30 minutes, once, and the maintenance dose as 0.25 mL/kg body weight = 5 mg/kg IV over 10 minutes or orally, every 24 hours beginning 24 hours after the loading dose. SALT WARNING, verbatim: 'The dose expressed as caffeine base is one-half the dose when expressed as caffeine citrate (20 mg caffeine citrate are equivalent to 10 mg caffeine base).' Every figure on this page is caffeine CITRATE. CONCENTRATION: 20 mg/ml, from the product's own name and independently confirmed by the SPC's volume column (20 mg/kg = 1.0 mL/kg; 5 mg/kg = 0.25 mL/kg). INSUFFICIENT RESPONSE: a second loading dose of 10-20 mg/kg maximum may be given after 24 hours, and higher maintenance doses of 10 mg/kg could be considered; the diagnosis of apnoea of prematurity may need to be reconsidered if patients do not respond adequately to a second loading dose or a maintenance dose of 10 mg/kg/day. RENAL IMPAIRMENT: there is increased potential for accumulation — a reduced daily maintenance dose is required and should be guided by plasma caffeine measurements; no dose recommendations have been established beyond that. HEPATIC: in very premature infants clearance does not depend on hepatic function, but in older infants hepatic disease may indicate a need to monitor plasma levels and may require dose adjustment. PREPARATION: the product may be used undiluted or diluted in sterile infusion solutions such as glucose 50 mg/ml (5%), sodium chloride 9 mg/ml (0.9%) or calcium gluconate 100 mg/ml (10%), immediately after withdrawal from the ampoule.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Paediatric weight-based calculator

THE 20 mg/kg FIGURE IS THE ONE-TIME LOADING DOSE — THE MAINTENANCE DOSE IS FOUR TIMES SMALLER (5 mg/kg every 24 hours). §4.2 verbatim: 'The recommended dose regimen in previously untreated infants is a loading dose of 20 mg caffeine citrate per kg body weight administered by slow intravenous infusion over 30 minutes, using a syringe infusion pump or other metered infusion device. After an interval of 24 hours, maintenance doses of 5 mg per kg body weight may be administered by slow intravenous infusion over 10 minutes every 24 hours. Alternatively, maintenance doses of 5 mg per kg body weight may be administered by oral administration, such as through a nasogastric tube every 24 hours.' The SPC's own dose table gives the loading dose as 1.0 mL/kg body weight = 20 mg/kg IV over 30 minutes, once, and the maintenance dose as 0.25 mL/kg body weight = 5 mg/kg IV over 10 minutes or orally, every 24 hours beginning 24 hours after the loading dose. SALT WARNING, verbatim: 'The dose expressed as caffeine base is one-half the dose when expressed as caffeine citrate (20 mg caffeine citrate are equivalent to 10 mg caffeine base).' Every figure on this page is caffeine CITRATE. CONCENTRATION: 20 mg/ml, from the product's own name and independently confirmed by the SPC's volume column (20 mg/kg = 1.0 mL/kg; 5 mg/kg = 0.25 mL/kg). INSUFFICIENT RESPONSE: a second loading dose of 10-20 mg/kg maximum may be given after 24 hours, and higher maintenance doses of 10 mg/kg could be considered; the diagnosis of apnoea of prematurity may need to be reconsidered if patients do not respond adequately to a second loading dose or a maintenance dose of 10 mg/kg/day. RENAL IMPAIRMENT: there is increased potential for accumulation — a reduced daily maintenance dose is required and should be guided by plasma caffeine measurements; no dose recommendations have been established beyond that. HEPATIC: in very premature infants clearance does not depend on hepatic function, but in older infants hepatic disease may indicate a need to monitor plasma levels and may require dose adjustment. PREPARATION: the product may be used undiluted or diluted in sterile infusion solutions such as glucose 50 mg/ml (5%), sodium chloride 9 mg/ml (0.9%) or calcium gluconate 100 mg/ml (10%), immediately after withdrawal from the ampoule.

Verify in a children's formulary

Contraindications

  • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
  • NOTE: this is the SPC's complete §4.3 — it lists no other contraindication. Apnoea of prematurity is a diagnosis of exclusion, and other causes of apnoea (central nervous system disorders, primary lung disease, anaemia, sepsis, metabolic disturbances, cardiovascular abnormalities or obstructive apnoea) should be ruled out or properly treated before starting treatment
  • Extreme caution must be exercised in newborns with seizure disorders — caffeine is a CNS stimulant and seizures have been reported in caffeine overdose (a §4.4 caution, not a §4.3 contraindication)
  • Use with caution in newborns with known cardiovascular disease, and administer with caution if there were unusual rhythm disturbances on the cardiotocograph before birth (a §4.4 caution, not a §4.3 contraindication)

Side effects

  • Common: hyperglycaemia
  • Common: tachycardia
  • Common: infusion site phlebitis, infusion site inflammation
  • Uncommon: convulsion
  • Uncommon: arrhythmia
  • Rare: hypersensitivity reaction
  • Not known: sepsis
  • Not known: hypoglycaemia, failure to thrive, feeding intolerance
  • Not known: irritability, jitteriness, restlessness, brain injury
  • Not known: deafness
  • Not known: increased left ventricular output and increased stroke volume
  • Not known: regurgitation, increased gastric aspirate, necrotising enterocolitis
  • Not known: urine output increased, urine sodium and calcium increased, haemoglobin decreased, thyroxine decreased
  • Effects are dose related and may necessitate measurement of plasma levels and dose reduction
  • NOTE: the SPC's §4.8 was truncated at the source-fetch limit in this capture — this list reproduces the tabulated reactions that were retrieved and may not be complete; consult the SPC

Monitoring

  • Plasma caffeine concentrations may need to be monitored periodically throughout treatment in cases of incomplete clinical response or signs of toxicity
  • Take blood samples just before the next dose in the case of therapeutic failure, and 2 to 4 hours after the previous dose when suspecting toxicity
  • A therapeutic plasma range has not been determined in the literature; caffeine levels in studies associated with clinical benefit ranged from 8 to 30 mg/L, and no safety concerns have normally been raised with plasma levels below 50 mg/L
  • Monitor and consider dose adjustment in: very premature infants (under 28 weeks gestational age and/or body weight under 1000 g), particularly on parenteral nutrition; hepatic or renal impairment; seizure disorders; known and clinically significant cardiac disease; co-administration of medicines known to interfere with caffeine metabolism; and infants whose mothers consume caffeine while providing breast milk
  • Measure BASELINE caffeine levels in infants whose mothers may have ingested large quantities of caffeine before delivery, and in infants previously treated with theophylline (which is metabolised to caffeine)
  • Monitor for necrotising enterocolitis — a possible association with methylxanthines has been reported, although a causal relationship has not been established
  • Duration: the optimal duration has not been established; in practice treatment is usually continued until the infant has reached a post-menstrual age of 37 weeks, by which time apnoea of prematurity usually resolves spontaneously. It is recommended that administration is stopped when the patient has had 5-7 days without a significant apnoeic attack
  • No dose tapering is required on cessation because of slow elimination in this population, but monitoring should continue for approximately one week after stopping because of the risk of recurrent apnoea
  • Breast-feeding mothers of treated newborns should not ingest caffeine-containing foods, beverages or medicines

Clinical monograph

How it works

It stimulates the respiratory centre and increases sensitivity to carbon dioxide, largely through antagonism of adenosine receptors, reducing apnoeic episodes.

Prescribing in practice

  • It has a narrow therapeutic range in neonates and can cause tachycardia, cardiac arrhythmias, jitteriness and feed intolerance if exposure is excessive.
  • Dosing in this vulnerable population should follow a children's formulary, and care is needed to distinguish caffeine citrate from caffeine base when prescribing.
  • Treatment is usually continued until the infant has been free of apnoea for a sustained period before discontinuation is considered.

Monitoring

Monitor heart rate, frequency of apnoeic episodes and feeding tolerance, with plasma levels checked only if toxicity or treatment failure is suspected.

Counselling the patient

  • This medicine helps your baby's breathing by reducing pauses in breathing.
  • The team will watch your baby's heart rate and feeding while on treatment.
  • Let staff know if you notice your baby becoming very jittery or unsettled.

Evidence & guidelines

The CAP trial showed caffeine therapy for apnoea of prematurity reduced bronchopulmonary dysplasia and improved neurodevelopmental outcomes.

Reference: CAP trial (NEJM 2006); BAPM Caffeine Guidelines; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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