Introduction
Cafcit (caffeine citrate) is a methylxanthine derivative used primarily for the treatment of apnea of prematurity in neonates. As a central nervous system stimulant, it represents one of the most commonly prescribed medications in neonatal intensive care units worldwide. This synthetic formulation provides precise dosing and improved stability compared to caffeine extracted from natural sources.
Mechanism of Action
Cafcit exerts its therapeutic effects through multiple mechanisms. Primarily, it acts as a competitive antagonist at adenosine A1 and A2A receptors in the brainstem. This adenosine receptor blockade leads to increased neuronal activity and respiratory drive. Additionally, caffeine inhibits phosphodiesterase enzymes, resulting in increased intracellular cyclic AMP levels, and mobilizes intracellular calcium stores. These combined actions stimulate the respiratory center, increase chemoreceptor sensitivity to carbon dioxide, and enhance diaphragmatic contractility.
Indications
- Treatment of apnea of prematurity in infants greater than 28 days gestational age
- Prophylaxis of apnea of prematurity in infants undergoing extubation
- Short-term treatment of apnea occurring in infants with bronchopulmonary dysplasia
Dosage and Administration
Loading dose: 20 mg/kg caffeine citrate (equivalent to 10 mg/kg caffeine base) IV or orally Maintenance dose: 5 mg/kg caffeine citrate (equivalent to 2.5 mg/kg caffeine base) IV or orally once daily Administration:- IV administration: Infuse over at least 30 minutes
- Oral administration: May be given via nasogastric or orogastric tube
- Dosing interval: Once every 24 hours
- Timing: Administer in the morning to minimize sleep disruption
- Renal impairment: Dose reduction required for significant impairment
- Hepatic impairment: Use with caution and consider dose reduction
- Geriatric and adult patients: Not indicated for use
Pharmacokinetics
Absorption: Well absorbed orally with bioavailability approximately 100% Distribution: Vd: 0.8-0.9 L/kg; crosses blood-brain barrier and placenta Protein binding: 25-36% Metabolism: Hepatic via CYP1A2-mediated demethylation to active metabolites Elimination: Half-life: 40-230 hours in preterm infants (age-dependent); primarily renal excretion Time to peak concentration: 30 minutes to 2 hours after administrationContraindications
- Hypersensitivity to caffeine or any component of the formulation
- History of cardiac arrhythmias
- Severe renal impairment without appropriate dose adjustment
- Seizure disorders (relative contraindication)
Warnings and Precautions
- Cardiac effects: May cause tachycardia, increased blood pressure, and arrhythmias
- Neurological effects: May lower seizure threshold and cause irritability
- Metabolic effects: May cause hyperglycemia and increased metabolic rate
- Gastrointestinal effects: May cause necrotizing enterocolitis (NEC) and feeding intolerance
- Renal effects: May increase renal calcium excretion
- Drug withdrawal: Abrupt discontinuation may cause rebound apnea
- Monitoring required: Continuous cardiorespiratory monitoring essential
Drug Interactions
- Ketoconazole, Cimetidine: May decrease caffeine clearance
- Phenobarbital, Phenytoin: May increase caffeine clearance
- Adenosine: Caffeine may antagonize effects
- Beta-blockers: Potential pharmacodynamic interaction
- Theophylline: Additive toxicity potential
- CYP1A2 inhibitors/inducers: May significantly affect caffeine levels
Adverse Effects
Common (≥10%):- Tachycardia
- Feeding intolerance
- Irritability
- Jitteriness
- Increased alertness
- Vomiting
- Gastric irritation
- Diuresis
- Hyperglycemia
- Weight loss
- Cardiac arrhythmias
- Seizures
- Necrotizing enterocolitis
- Intracranial hemorrhage (theoretical risk)
- Hepatotoxicity
Monitoring Parameters
- Continuous: Cardiorespiratory monitoring for apnea, bradycardia, desaturation
- Cardiac: Heart rate, rhythm, blood pressure (at least every 6-8 hours)
- Neurological: Assessment for jitteriness, irritability, seizure activity
- Metabolic: Serum glucose monitoring, electrolyte status
- Therapeutic drug monitoring: Serum caffeine levels (target range: 5-20 mcg/mL)
- Renal function: BUN, creatinine, urine output
- Growth parameters: Daily weight, head circumference
Patient Education
For parents/caregivers:- Understand that Cafcit is used to help regulate breathing patterns
- Recognize potential side effects: increased alertness, irritability, feeding changes
- Maintain consistent administration schedule as directed
- Do not discontinue medication abruptly without medical supervision
- Report any concerning symptoms: excessive irritability, vomiting, rapid heart rate
- Understand that multiple weeks of therapy are typically required
- Know that dose adjustments are based on infant's weight and response
References
1. Schmidt B, et al. Caffeine Therapy for Apnea of Prematurity. N Engl J Med. 2006;354(20):2112-2121. 2. Cafcit [package insert]. Lake Forest, IL: Akorn Pharmaceuticals; 2021. 3. Charles BG, et al. Population pharmacokinetics of caffeine in preterm neonates. Eur J Clin Pharmacol. 2008;64(9):899-906. 4. Henderson-Smart DJ, Steer P. Prophylactic caffeine to prevent postoperative apnea in preterm infants. Cochrane Database Syst Rev. 2001;(4):CD000048. 5. Natarajan G, et al. Update on pharmacologic management of neonatal abstinence syndrome. J Perinatol. 2011;31(11):692-701. 6. American Academy of Pediatrics Committee on Fetus and Newborn. Apnea of prematurity. Pediatrics. 2016;137(1):e20153757.