CAFCIT
Clinical safety rating
cautionComprehensive clinical and safety monograph for CAFCIT (CAFCIT).
Caffeine citrate is a central nervous system stimulant. It competitively blocks adenosine receptors (A1 and A2A subtypes), leading to increased neuronal firing and release of neurotransmitters such as dopamine and norepinephrine. In neonates, it stimulates respiratory centers, increases minute ventilation, and improves sensitivity to hypercapnia.
| Metabolism | Primarily hepatic via cytochrome P450 1A2 (CYP1A2) to paraxanthine, theobromine, and theophylline. Minor metabolism via CYP3A4, CYP2E1, and N-acetyltransferase. |
| Excretion | Renal: approximately 86% as unchanged drug and metabolites (paraxanthine, theophylline, theobromine) with about 1% unchanged; biliary/fecal: negligible. |
| Half-life | Terminal elimination half-life: In neonates (postmenstrual age 28-44 weeks), 40-230 hours (mean ~100 hours); in adults, 3-6 hours. Clinical context: Prolonged in preterm neonates due to immature hepatic function. |
| Protein binding | Approximately 36% bound to serum albumin in neonates; in adults, about 50% bound to albumin. |
| Volume of Distribution | Neonates: 0.8-1.0 L/kg; adults: 0.4-0.6 L/kg. Clinical meaning: Reflects distribution into body water, with higher Vd in neonates due to higher total body water. |
| Bioavailability | Oral: 85-100% (well absorbed); intravenous: 100%. |
| Onset of Action | Intravenous: within 15-30 minutes for apnea of prematurity; oral: 30-60 minutes. |
| Duration of Action | Intravenous: 24-48 hours for apnea reduction; oral: similar. Clinical note: Due to long half-life, dosing every 24 hours is typical in neonates. |
| Molecular Weight | 212.2 Da (caffeine citrate; caffeine base: 194.19 Da) |
Caffeine citrate: IV or PO, loading dose 20 mg/kg (caffeine base) once, then maintenance 5 mg/kg (caffeine base) once daily. Onset of action: 15-30 minutes IV; peak effect: 30-120 minutes. Duration: 40-100 hours.
| Dosage form | SOLUTION |
| Renal impairment | No specific GFR-based dose adjustments are recommended; however, monitor for accumulation in renal impairment due to prolonged half-life (up to 100 hours in neonates). Consider reducing dose or extending interval if severe renal dysfunction. |
| Liver impairment | No specific Child-Pugh based adjustments provided. Caution in severe hepatic impairment due to prolonged clearance. Monitor for adverse effects. |
| Pediatric use | Neonates (≤28 days): Caffeine citrate IV or PO; loading dose 20 mg/kg (caffeine base) once, then maintenance 5 mg/kg (caffeine base) once daily starting 24 hours after loading. Adjust to maintain therapeutic plasma levels (5-25 mg/L). Infants >28 days and children: dosing not established for apnea of prematurity; use weight-based dosing with caution. |
| Geriatric use | No specific dose adjustments in elderly; consider lower initial doses due to possible reduced clearance and increased sensitivity to CNS stimulation. |
| 1st trimester | Use only if clearly needed; caffeine citrate crosses placenta and may cause fetal tachycardia or arrhythmias. Limited human data, but animal studies show reduced fetal weight and delayed ossification at high doses. |
| 2nd trimester | Use with caution; monitor fetal heart rate. Potential for caffeine accumulation in fetus due to immature metabolism. |
| 3rd trimester | Avoid near term; neonatal caffeine half-life significantly prolonged, risk of caffeine toxicity (jitteriness, tachypnea, poor feeding). |
Clinical note
Comprehensive clinical and safety monograph for CAFCIT (CAFCIT).
| Placental transfer | Caffeine readily crosses the placenta with fetal concentrations similar to maternal. Fetal metabolism is immature, leading to prolonged exposure. |
| Breastfeeding | Caffeine citrate is excreted into breast milk in small amounts (0.06-1.5% of maternal dose). Infant exposure is generally low but may accumulate in preterm infants. Caution with high maternal doses; monitor infant for irritability or sleep disturbances. |
| Lactation Rating | L2 (Probably Compatible) |
| Teratogenic Risk | Caffeine (Cafcit) is FDA Pregnancy Category C. In first trimester, studies suggest possible association with low birth weight but not major malformations. Avoid high doses. In second and third trimesters, caffeine crosses placenta; high maternal intake linked with reduced uteroplacental blood flow, fetal growth restriction, and preterm birth. Avoid excessive intake. |
| Fetal Monitoring | Monitor maternal heart rate/BP, especially in hypertensive disorders. Fetal: ultrasound for growth if prolonged high dose; assess for fetal tachycardia if maternal levels high. Neonatal: observe for jitteriness, apnea (especially if used for apnea of prematurity). |
| Fertility Effects | Moderate caffeine intake (200-300 mg/day) may delay conception in some women; high intake (>500 mg/day) associated with decreased fertility. No evidence of permanent reproductive harm. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to caffeine or any componentHistory of cardiac arrhythmias (e.g., ventricular tachycardia)Uncontrolled seizure disorder
| Precautions | Use with caution in neonates with seizure disorders, as caffeine may lower seizure threshold., Monitor for signs of toxicity including tachycardia, irritability, and feeding intolerance., Renal impairment may prolong half-life; adjust dose in severe renal dysfunction., Hepatic impairment may reduce clearance., May exacerbate gastroesophageal reflux disease (GERD). |
| Food/Dietary | No significant food interactions. Avoid caffeine-containing products (coffee, tea, soda, chocolate) due to additive stimulant effects. |
| Clinical Pearls | CAFCIT (caffeine citrate) is used for apnea of prematurity. Loading dose: 20 mg/kg IV/PO; maintenance: 5-10 mg/kg/day. Therapeutic levels 8-20 mg/L; monitor for tachycardia, feeding intolerance. Reduce dose with hepatic impairment. Discontinue if seizures occur. |
| Patient Advice | This medication helps your baby breathe more regularly by stimulating the respiratory center. · It may cause increased heart rate, jitteriness, or feeding problems. · Do not give extra caffeine (coffee, tea, cola) while on this medicine. · Report any signs of irritability, vomiting, or seizures to the doctor immediately. |
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