Peyona (Caffeine Citrate)
Central nervous system stimulant for treating apnea of prematurity in newborns
Quick Facts About Peyona
Key Takeaways About Peyona
- Hospital-only medication: Peyona must only be used in a neonatal intensive care unit (NICU) with proper monitoring equipment and experienced staff
- Proven efficacy in premature infants: Caffeine citrate significantly reduces apnea episodes and has been shown to improve long-term neurodevelopmental outcomes
- Two routes of administration: Can be given intravenously (loading and maintenance doses) or orally (maintenance doses only)
- Breastfeeding mothers should avoid caffeine: Caffeine passes into breast milk and can add to the baby's caffeine load
- Regular blood monitoring required: Caffeine blood levels should be checked throughout treatment to prevent toxicity
What Is Peyona and What Is It Used For?
Peyona contains the active substance caffeine citrate, a central nervous system stimulant belonging to the methylxanthine group. It is used to treat apnea of prematurity — brief episodes where premature babies stop breathing because their brainstem respiratory center is not yet fully mature.
Apnea of prematurity is a common condition affecting premature infants, particularly those born before 34 weeks of gestational age. During an apneic episode, the baby ceases to breathe for 15–20 seconds or longer, which can lead to a drop in oxygen saturation and heart rate (bradycardia). These episodes occur because the neural circuits controlling breathing in the brainstem are still immature at birth in preterm infants.
Caffeine citrate works by stimulating the central nervous system, specifically the respiratory centers in the brainstem. As a competitive antagonist of adenosine receptors (primarily A1 and A2A subtypes), it increases respiratory drive, enhances diaphragmatic contractility, and improves the sensitivity of the chemoreceptors that detect carbon dioxide levels in the blood. This pharmacological action results in more regular and sustained breathing patterns.
The landmark Caffeine for Apnea of Prematurity (CAP) trial, one of the largest randomized controlled trials in neonatal medicine, demonstrated that caffeine citrate not only reduces apnea episodes effectively but also decreases the incidence of bronchopulmonary dysplasia (BPD) and improves neurodevelopmental outcomes at 18–21 months of corrected age. These findings have made caffeine citrate one of the standard-of-care medications in neonatal intensive care worldwide.
Peyona is approved by the European Medicines Agency (EMA) and is indicated specifically for the treatment of primary apnea of prematurity in newborn infants. It is manufactured by Chiesi Farmaceutici S.p.A. and is available as a clear, colorless solution in glass ampoules, supplied in packs of 10 ampoules. Each milliliter contains 20 mg of caffeine citrate, equivalent to 10 mg of caffeine base.
Before starting Peyona treatment, the physician must rule out or appropriately treat other potential causes of apnea, such as sepsis, metabolic disorders, intracranial abnormalities, or airway obstruction. Peyona is specifically indicated for primary (idiopathic) apnea of prematurity caused by brainstem immaturity.
What Should You Know Before Peyona Is Given to Your Baby?
Before treatment with Peyona begins, the baby's medical team must evaluate for contraindications, assess potential drug interactions, and consider relevant precautions. Parents should inform the medical team of any known allergies, concurrent medications, or maternal caffeine consumption.
Contraindications
Peyona must not be used if the newborn is allergic (hypersensitive) to caffeine citrate or any of the other ingredients in the formulation. The excipients include citric acid, sodium citrate, and water for injections. Allergic reactions to caffeine are extremely rare but have been reported. Signs of an allergic reaction may include rash, swelling, or breathing difficulties.
Warnings and Precautions
The treating physician should be informed and exercise caution in the following situations:
- Seizures: If the baby has a history of seizures or is at risk of seizure activity, caffeine may lower the seizure threshold
- Cardiac disease: Caffeine can increase heart rate and may exacerbate underlying cardiac conditions
- Renal or hepatic impairment: Immature or impaired kidney or liver function can affect caffeine metabolism and excretion, potentially leading to accumulation and toxicity
- Gastroesophageal reflux: Caffeine may worsen gastroesophageal reflux, which is common in premature infants
- Increased urine output: Caffeine has mild diuretic properties and may increase urine production
- Poor weight gain or feeding intolerance: These should be monitored closely as caffeine can affect feeding patterns
- Maternal caffeine consumption: If the mother consumed significant amounts of caffeine before delivery, the baby may already have elevated caffeine levels at birth
There is a potential increased risk of necrotizing enterocolitis (NEC), a serious intestinal condition with bloody stools, when Peyona is used in combination with medications that reduce gastric acid secretion, such as histamine H2-receptor blockers (e.g., ranitidine) or proton pump inhibitors (e.g., omeprazole). The medical team should weigh this risk carefully.
Breastfeeding Considerations
If the mother is breastfeeding while her baby is being treated with Peyona, she should avoid drinking coffee or consuming other products with high caffeine content. Caffeine is excreted in breast milk at concentrations approximately 50–80% of maternal serum levels. Since the baby is already receiving therapeutic doses of caffeine, additional caffeine from breast milk could lead to excessive plasma concentrations and increase the risk of side effects such as tachycardia, jitteriness, and irritability.
Common dietary sources of caffeine that breastfeeding mothers should limit include coffee, tea, cola drinks, energy drinks, and chocolate. The medical team can provide guidance on acceptable caffeine intake levels during the treatment period.
Peyona contains less than 1 mmol (23 mg) of sodium per dose, making it essentially sodium-free. This is generally not a concern even in very low birth weight infants with restricted sodium intake.
How Does Peyona Interact with Other Drugs?
Peyona can interact with several medications commonly used in neonatal care. The most significant interactions involve theophylline, doxapram, cimetidine, ketoconazole, phenobarbital, and phenytoin. The medical team must be informed of all medications the baby is receiving.
Drug interactions in neonates are particularly important because premature infants have immature hepatic enzyme systems (particularly CYP1A2) that metabolize caffeine. This results in a prolonged half-life of approximately 72–96 hours in premature neonates compared to 5–6 hours in adults. Any drug that affects these metabolic pathways can significantly alter caffeine levels.
| Interacting Drug | Used For | Type of Interaction | Clinical Significance |
|---|---|---|---|
| Theophylline | Breathing difficulties | Additive methylxanthine effects; caffeine is a metabolite of theophylline | Major — avoid concurrent use or monitor closely |
| Doxapram | Respiratory stimulation | Additive CNS stimulation | Major — may increase risk of toxicity |
| Cimetidine | Gastric ulcer disease | Inhibits caffeine metabolism (CYP1A2 inhibitor) | Moderate — may increase caffeine levels |
| Ketoconazole | Fungal infections | Inhibits caffeine metabolism | Moderate — dose adjustment may be needed |
| Phenobarbital | Epilepsy / seizure control | Induces caffeine metabolism (CYP1A2 inducer) | Moderate — may reduce caffeine efficacy |
| Phenytoin | Epilepsy / seizure control | Induces caffeine metabolism | Moderate — may reduce caffeine efficacy |
| H2-blockers / PPIs | Gastric acid reduction | May increase risk of necrotizing enterocolitis (NEC) | Major — use with extreme caution |
If the baby has previously been treated with theophylline, this is particularly important to communicate to the medical team, as theophylline is metabolized to caffeine in neonates. Concurrent use or sequential use without an adequate washout period can lead to supratherapeutic caffeine levels and increase the risk of toxicity.
The immature hepatic metabolism in premature infants means that even drugs classified as having "moderate" interactions can have clinically significant effects. The medical team will monitor caffeine plasma levels and adjust doses accordingly when any of these interacting drugs are co-administered.
What Is the Correct Dosage of Peyona?
Peyona dosing is based on body weight. The loading dose is 20 mg/kg of caffeine citrate (equivalent to 10 mg/kg caffeine base) given intravenously. The maintenance dose is 5 mg/kg of caffeine citrate (equivalent to 2.5 mg/kg caffeine base) given once daily, either intravenously or orally.
Peyona must only be used in a neonatal intensive care unit (NICU) where adequate equipment for patient monitoring and surveillance is available. Treatment should be initiated under the supervision of a physician experienced in neonatal intensive care. The physician will calculate the exact dose based on the baby's body weight.
Loading Dose (First Dose)
20 mg/kg body weight of caffeine citrate (equivalent to 1 ml/kg body weight), administered as a controlled intravenous infusion over 30 minutes using a syringe pump or metered infusion device.
Maintenance Dose (Starting 24 Hours After Loading Dose)
5 mg/kg body weight of caffeine citrate (equivalent to 0.25 ml/kg body weight), given once every 24 hours. The maintenance dose can be administered either:
- Intravenously over 10 minutes, or
- Orally (by mouth or via nasogastric tube)
| Dose Type | Caffeine Citrate | Caffeine Base | Volume | Route |
|---|---|---|---|---|
| Loading dose | 20 mg/kg | 10 mg/kg | 1 ml/kg | IV infusion over 30 min |
| Maintenance dose | 5 mg/kg every 24h | 2.5 mg/kg every 24h | 0.25 ml/kg | IV over 10 min or oral |
Blood Level Monitoring
To prevent toxic effects, the physician may need to regularly check caffeine levels in the baby's blood throughout the course of treatment. Therapeutic plasma concentrations of caffeine typically range from 8 to 30 mg/L (micrograms per milliliter). Levels above 40–50 mg/L are associated with increased toxicity risk. Monitoring is especially important in infants with hepatic or renal impairment, those receiving interacting medications, or when the clinical response is suboptimal.
Treatment Duration
The treating physician determines the exact duration of treatment based on the baby's clinical response. Typically, if the baby has been free of apnea episodes for 5 to 7 consecutive days, the physician will consider discontinuing treatment. In many cases, treatment is continued until the infant reaches approximately 33–35 weeks of corrected gestational age, by which time the brainstem respiratory centers have usually matured sufficiently.
Overdose
If a baby receives too much caffeine citrate, the following symptoms may occur:
- Fever and rapid breathing (tachypnea)
- Jitteriness, muscle tremors, and seizures
- Vomiting and feeding intolerance
- High blood sugar (hyperglycemia)
- Low potassium levels (hypokalemia)
- Elevated blood urea nitrogen
- Elevated white blood cell count (leukocytosis)
- Tachycardia and cardiac arrhythmias
If overdose is suspected, Peyona treatment should be stopped immediately. There is no specific antidote for caffeine toxicity. Management is supportive and may include exchange transfusion in severe cases. The physician will monitor vital signs, correct electrolyte imbalances, and treat seizures if they occur.
What Are the Side Effects of Peyona?
Like all medicines, Peyona can cause side effects, though not all patients experience them. It can be difficult to distinguish medication side effects from common complications of prematurity. The most common side effects include local reactions at the infusion site, tachycardia, and changes in blood sugar levels.
Side effects in premature neonates receiving caffeine citrate must be interpreted carefully, as many of the observed effects overlap with the typical medical challenges faced by premature infants. The medical team continuously monitors for both expected complications of prematurity and potential medication-related adverse effects.
Common Side Effects
May affect up to 1 in 10 patients
- Local inflammatory reactions at the infusion site
- Tachycardia (rapid heartbeat)
- Hyperglycemia (elevated blood sugar levels)
Uncommon Side Effects
May affect up to 1 in 100 patients
- Seizures (central nervous system stimulation)
- Cardiac arrhythmia (irregular heartbeat)
Rare Side Effects
May affect up to 1 in 1,000 patients
- Allergic reactions
Frequency Not Known
Cannot be estimated from available data
- Necrotizing enterocolitis (NEC) — serious intestinal disease with bloody stools
- Sepsis (blood infection)
- Hypoglycemia (low blood sugar), impaired growth, feeding intolerance
- Irritability, nervousness, and restlessness
- Brain injury
- Deafness
- Gastroesophageal reflux, increased aspiration of gastric contents
- Increased urine output, increased urinary sodium and calcium excretion
- Decreased hemoglobin levels (after prolonged treatment)
- Decreased thyroid hormone levels (at start of treatment)
It is important to note that many of the effects listed under "frequency not known" are conditions that frequently occur in premature infants regardless of caffeine treatment. Establishing a direct causal relationship is often challenging. The overall safety profile of caffeine citrate in premature neonates is well-established, with the benefits of reducing apnea generally outweighing the risks.
Parents and caregivers should report any suspected side effects to the baby's medical team immediately. Healthcare professionals are encouraged to report suspected adverse reactions through their national pharmacovigilance systems to enable continuous monitoring of the medicine's benefit–risk balance.
How Should Peyona Be Stored?
Peyona should be stored out of sight and reach of children, used before the expiry date, and does not require any special storage conditions. Once opened, the solution should be used immediately.
Peyona does not have any special storage temperature requirements and can be stored at room temperature. However, as with all parenteral solutions, the ampoules should be visually inspected for particulate matter and discoloration before administration. The solution should be clear and colorless. Any ampoule showing visible particles, cloudiness, or discoloration should not be used.
Once an ampoule is opened, the solution should be used immediately. Any remaining solution that is not used should be discarded. The product should not be used after the expiry date printed on the label, where the expiry date refers to the last day of the stated month. Peyona is supplied as glass ampoules containing either 1 ml or 3 ml of solution, packed in cartons of 10 ampoules.
What Does Peyona Contain?
Each milliliter of Peyona contains 20 mg of caffeine citrate (equivalent to 10 mg of caffeine base). The other ingredients are citric acid, sodium citrate, and water for injections.
The active substance in Peyona is caffeine citrate. The relationship between caffeine citrate and caffeine base is important for dosing accuracy: 20 mg of caffeine citrate is equivalent to 10 mg of caffeine base (a 2:1 ratio). All dosing recommendations for Peyona are expressed in terms of caffeine citrate, but some other caffeine products may express doses in terms of caffeine base, so healthcare providers must be careful to use the correct units.
The ampoule sizes and their caffeine content are:
- 1 ml ampoule: contains 20 mg caffeine citrate (equivalent to 10 mg caffeine base)
- 3 ml ampoule: contains 60 mg caffeine citrate (equivalent to 30 mg caffeine base)
The excipients (inactive ingredients) serve specific pharmaceutical functions: citric acid acts as a pH buffer and stabilizer, sodium citrate functions as a buffering agent to maintain the solution's pH within an acceptable range, and water for injections serves as the solvent. The final solution has a near-neutral pH suitable for both intravenous and oral administration.
Peyona is manufactured by Alfasigma S.p.A. (Alanno, Italy) and Chiesi Pharmaceuticals GmbH (Vienna, Austria). The marketing authorization is held by Chiesi Farmaceutici S.p.A. (Parma, Italy).
Frequently Asked Questions About Peyona
Peyona (caffeine citrate) is used to treat apnea of prematurity, a condition in which premature babies have episodes where they temporarily stop breathing. These breathing pauses occur because the respiratory control center in the baby's brainstem is not yet fully developed. Caffeine citrate stimulates the brain's respiratory centers, reducing the frequency and severity of these episodes. It is used exclusively in neonatal intensive care units (NICUs) under specialist supervision.
Peyona is first given as a loading dose of 20 mg/kg body weight via controlled intravenous infusion over 30 minutes. Starting 24 hours later, a maintenance dose of 5 mg/kg is given once daily. The maintenance dose can be given either intravenously (over 10 minutes) or orally. The oral route is often preferred once the baby tolerates enteral feeding, as it is less invasive. A syringe pump or metered infusion device is used for intravenous administration to ensure precise dosing.
The most common side effects (affecting up to 1 in 10 patients) include local inflammatory reactions at the infusion site, tachycardia (rapid heartbeat), and hyperglycemia (elevated blood sugar). Less common side effects include seizures and cardiac arrhythmia. Many observed effects in premature infants overlap with typical complications of prematurity, making it challenging to attribute them solely to caffeine treatment. Overall, caffeine citrate has a well-established safety profile in neonatal medicine.
Breastfeeding mothers should avoid coffee and other high-caffeine products while their baby is being treated with Peyona. Caffeine is excreted in breast milk at concentrations that are 50–80% of maternal serum levels. Since the baby is already receiving therapeutic doses of caffeine, additional caffeine from breast milk could increase the risk of side effects such as tachycardia, jitteriness, and irritability. The medical team can advise on acceptable levels of caffeine intake during the treatment period.
The duration of treatment is individualized and determined by the physician. Generally, if the baby has been free of apnea episodes for 5–7 consecutive days, the doctor will consider stopping treatment. Treatment is often continued until the infant reaches approximately 33–35 weeks of corrected gestational age, when the brainstem respiratory centers have typically matured enough to maintain normal breathing. The physician may also consider a gradual dose reduction rather than abrupt discontinuation.
Yes. The Caffeine for Apnea of Prematurity (CAP) trial, one of the largest studies in neonatal medicine, showed that caffeine therapy not only reduces apnea episodes but also decreases the rate of bronchopulmonary dysplasia (BPD) and improves neurodevelopmental outcomes at 18–21 months of corrected age. Follow-up studies at 5 and 11 years of age have also shown improved motor function and reduced rates of developmental coordination disorder in children who received caffeine treatment as neonates.
References
This article is based on the following peer-reviewed sources and official guidelines:
- European Medicines Agency (EMA). Peyona (caffeine citrate) — Summary of Product Characteristics. Last updated 2024. Available at: ema.europa.eu/en/medicines/human/EPAR/peyona
- Schmidt B, Roberts RS, Davis P, et al. Caffeine therapy for apnea of prematurity. New England Journal of Medicine. 2006;354(20):2112–2121. DOI: 10.1056/NEJMoa054065
- Schmidt B, Roberts RS, Davis P, et al. Long-term effects of caffeine therapy for apnea of prematurity. New England Journal of Medicine. 2007;357(19):1893–1902. DOI: 10.1056/NEJMoa073679
- Schmidt B, Roberts RS, Anderson PJ, et al. Academic performance, motor function, and behavior 11 years after neonatal caffeine citrate therapy for apnea of prematurity. JAMA Pediatrics. 2017;171(6):564–572. DOI: 10.1001/jamapediatrics.2017.0238
- Henderson-Smart DJ, De Paoli AG. Methylxanthine treatment for apnoea in preterm infants. Cochrane Database of Systematic Reviews. 2010;(12):CD000140. DOI: 10.1002/14651858.CD000140.pub2
- World Health Organization. WHO Model List of Essential Medicines for Children — 9th List. 2023. Available at: who.int
- British National Formulary for Children (BNFc). Caffeine citrate monograph. NICE Evidence Services. Available at: bnfc.nice.org.uk
About the Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, consisting of licensed specialist physicians with expertise in neonatology, pediatrics, and clinical pharmacology.
Medical Writing
Content created by physicians with clinical experience in neonatal intensive care and pharmacotherapy. All medical claims are supported by peer-reviewed evidence (Level 1A).
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Independently reviewed by the iMedic Medical Review Board following WHO, EMA, and AAP guidelines. Reviewed for accuracy, completeness, and clinical relevance.
Last medical review: . Next scheduled review: January 2027. Editorial standards: iMedic Editorial Standards.