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Caffeine citrate parenteral

Updated 2 Feb 2023 | Respiratory stimulants


Parenteral formulations of caffeine citrate.

Drugs List

  • caffeine citrate 10mg/ml solution for infusion ampoule
  • caffeine citrate 20mg/ml solution for infusion
  • GENCEBOK 10mg/1ml solution for infusion ampoule
  • PEYONA (CAFFEINE CITRATE) 20mg/ml solution for infusion
  • Therapeutic Indications


    Apnoea of prematurity


    The MHRA has recommended that doses specified when prescribing should always be expressed as caffeine citrate because of a risk of confusion and potential for dosing errors (2 mg caffeine citrate is equivalent to 1 mg caffeine base).


    Loading dose
    20 mg/kg by slow intravenous infusion over 30 minutes. An interval of 24 hours should pass before maintenance dose.

    Those with insufficient response can receive a second loading dose 24 hours after the first loading dose.

    Second loading dose: 10 to 20 mg/kg by slow intravenous infusion.

    Maintenance dose
    5 mg/kg by slow intravenous infusion over 10 minutes every 24 hours.

    A higher maintenance dose can be considered in cases of insufficient response.

    Higher maintenance dose: 10 mg/kg by slow intravenous infusion over 10 minutes every 24 hours.

    Additional Dosage Information

    If there is no clinical response to the second loading dose or maintenance dose of 10mg/kg/day, caffeine blood levels should be measured before further doses are given. Failure to respond could be an indication of another cause of apnoea. In cases of therapeutic failure, blood samples should be taken before the next dose and 2 to 4 hours after previous dose when monitoring for suspected toxicity. Plasma levels should not normally exceed 50 micrograms/ml (optimally 10 to 30 micrograms/ml).

    If the patient has recurrent apnoea, caffeine citrate administration can be restarted with either a maintenance dose or a half loading lose, depending upon the time interval from stopping caffeine citrate to recurrence of apnoea.


    For intravenous infusion by controlled intravenous infusion, using a syringe infusion pump or other metered infusion device only.

    Caffeine citrate can be either used without dilution or diluted in sterile solutions for infusion such as glucose 50mg/ml (5%), or sodium chloride 9mg/ml (0.9%) or calcium gluconate 100mg/ml (10%) immediately after withdrawal from the ampoule.

    Maintenance dose may be administered orally as an alternative to injection (no dosage adjustment), such as through a nasogastric tube every 24 hours.


    None known

    Precautions and Warnings

    Cardiac arrhythmias
    Cardiac disorder
    Gastroesophageal reflux
    Hepatic impairment
    Renal impairment

    Avoid caffeine while breastfeeding: May affect infant's baseline levels
    Caffeine intake prior to birth may affect infant's baseline levels
    Doses must always be stated as caffeine citrate
    Treatment to be initiated and supervised by a specialist
    Administration carried out in centres with intensive care facilities
    Discard any unused portion
    For single use only
    Monitor fluid and electrolyte status
    Monitor plasma concentrations of this drug
    Monitor plasma levels and adapt dose in patients with hepatic impairment
    Monitor plasma levels and adapt dose in patients with renal impairment
    May aggravate gastro-oesophageal reflux

    Baseline plasma caffeine concentrations should be measured prior to initiation of the treatment with caffeine citrate in cases where there may be pre-existing caffeine in the blood of neonates whose mothers may have ingested large quantities of caffeine prior to delivery, or neonates who have previously been treated with theophylline (metabolised to caffeine).

    Prior to treatment, exclude other causes of apnoea such as central nervous system disorders, primary lung disease, anaemia, sepsis, metabolic disturbances, cardiovascular abnormalities, or obstructive apnoea.

    Monitor patient for 1 week after treatment due to the risk of apnoea recurrence after cessation of caffeine citrate. The prolonged half-life of caffeine and the potential for accumulation requires patients to be monitored.

    Discontinue treatment if the patient has not experienced significant apnoeic attack for 5 to 7 days.

    Treatment should continue until the child has reached a gestational age of 37 weeks, by which time apnoea of prematurity usually resolves spontaneously. Treatment may continue beyond this point, based on clinical judgement in individual cases, considering factors such as response to treatment and presence of apnoeic episodes.

    Dose adjustment may be needed for at risk patients such as very premature infants (less than 28 weeks gestational age and/or body weight below 1kg), infants whose mothers consume caffeine while providing breast milk, infants with renal and/or hepatic impairment, seizure disorder, clinically significant cardiac disorders, and patients on treatments that can interfere with caffeine metabolism.

    Pregnancy and Lactation


    Not indicated in patients of child bearing age, relevant data is not available.


    Not indicated in patients of child bearing age, relevant data is not available.

    Breastfeeding mothers of neonates treated with caffeine citrate should not ingest caffeine-containing foods and beverages or medicinal products containing caffeine, since caffeine is excreted into breastmilk.

    Side Effects

    Brain injury
    Decrease in blood thyroxine values
    Decrease in haemoglobin
    Gastric aspiration
    Gastroesophageal reflux
    Hypersensitivity reactions
    Increased calcium excretion
    Increased left ventricular output
    Increased sodium excretion
    Increased stroke volume
    Increased urination
    Inflammation (injection site)
    Necrotising enterocolitis
    Phlebitis (injection site)
    Suppressed erythropoietin synthesis


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: September 2013

    Reference Sources

    Summary of Product Characteristics: Caffeine Citrate 10 mg/ml solution for injection. Viridian Pharma Ltd. Revised February 2008.

    Summary of Product Characteristics: Gencebok 10 mg/ml solution for infusion. Gennisium Pharma. Revised January 2021.

    Summary of Product Characteristics: Peyona (caffeine citrate) 20 mg/ml solution for infusion and oral solution. Chiesi Ltd. Revised January 2012.

    NICE Evidence Services Available at: Last accessed: 16 December 2022

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