Title Caffeine Citrate Dose
Loading dose: 20 to 25 mg/kg of caffeine citrate IV over 30 minutes or orally.
(Equivalent to 10 to 12.5 mg/kg caffeine base).
Maintenance dose: 5 to 10 mg/kg per dose of caffeine citrate IV slow push or orally every 24 hours. (Equivalent to 2.5 to 5 mg/kg caffeine base).
Maintenance dose should be started 24 hours after the loading dose.
May consider an additional loading dose and higher maintenance doses if able to monitor serum concentrations.
(Please note that emphasis has changed to caffeine citrate due to commercially
available product. This product (Cafcit®) may be administered both intravenously and orally).
Uses
Treatment of neonatal apnea, including post-extubation and post-anesthesia. (More favorable therapeutic index than aminophylline).
Pharmacology
The pharmacological effects of caffeine are mediated by its antagonism of the actions of adenosine at cell surface receptors. It is rapidly distributed in the brain, with CNS levels approximating plasma levels. Caffeine increases the respiratory center output, chemoreceptor sensitivity to CO2, smooth muscle relaxation, and cardiac output.
Oxygen consumption may be increased and weight gain may be reduced. Renal effects include diuresis and increased urinary calcium excretion. Orally administered caffeine citrate is rapidly and completely absorbed. There is almost no first-pass metabolism. In
neonates, approximately 86% is excreted unchanged in the urine, with the remainder metabolized via the CYP1A2 enzyme system. The serum half-life of caffeine ranges from 40 to 230 hours, decreasing with advancing postmenstrual age until 60 weeks PMA. Half-life is prolonged in infants with cholestatic hepatitis.
Adverse Effects
Adverse effects are usually mild, and include restlessness, vomiting, and functional cardiac symptoms. There has been a suggested association with NEC, but causality has never been proven. Loading doses of 25 mg/kg caffeine (50 mg/kg caffeine citrate) have been reported to decrease cerebral and intestinal blood flow velocity.
Monitoring
Baseline caffeine levels are recommended in neonates previously treated with theophylline and neonates born to mothers who consumed caffeine prior to delivery.
If using the suggested doses, measuring serum concentrations is probably not
necessary. Monitoring of serum drug concentration should be based on a trough level determined on approximately day 5 of therapy. Therapeutic trough serum concentration is 5 to 25 mcg/mL. Concentrations greater than 40 to 50 mcg/mL are toxic. Assess for agitation. Monitor heart rate; consider withholding dose if greater than 180 beats per minute.
Special Considerations/Preparation
Both Cafcit® Oral Solution and Cafcit® Injection for intravenous administration are preservative free and available in 3-mL single use vials. Each mL of Cafcit® contains 20 mg of caffeine citrate (equivalent to 10 mg caffeine base). Store at room
temperature.
Alternatively, an oral solution may be prepared by dissolving 2.5 g of caffeine anhydrous powder in 250 mL of water, yielding a final concentration of 10 mg/mL.
Solution is stable for 4 weeks refrigerated. Crystals form when stored at low
temperature but dissolve at room temperature without loss of potency. Do not freeze.
Solution Compatibility
D5W and D50W.
Terminal Injection Site Compatibility
Dex/AA solutions. Alprostadil, amikacin, aminophylline, calcium gluconate, cefotaxime, cimetidine, clindamycin, dexamethasone, dobutamine, dopamine,
doxapram, epinephrine, fentanyl, gentamicin, heparin (concentration less than or equal to 1 unit/mL), isoproterenol, lidocaine, metoclopramide, morphine, nitroprusside, pancuronium, penicillin G, phenobarbital, sodium bicarbonate, and vancomycin.
Terminal Injection Site Incompatibility
Acyclovir, furosemide, ibuprofen lysine, lorazepam, nitroglycerin, and oxacillin.
References
Schmidt B, Roberts RS, Davis P, et al: Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 2007;357:1893-1902.
Schmidt B, Roberts RS, Davis P, et al: Caffeine therapy for apnea of prematurity. N Engl J Med 2006;354:2112-2121.
Steer P, Flenady V, Shearman A, et al: High dose caffeine citrate for extubation of preterm infants: a randomized controlled trial. Arch Dis Child Fetal Neonatal Ed 2004;89:F499-F503.
Comer AM, Perry CM, Figgitt DP: Caffeine citrate: A review of its use in apnoea of prematurity. Paediatr Drugs 2001;3:61-70.
Bauer J, Maier K, Linderkamp O, Hentschel R: Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea. Pediatrics 2001;107:660-663.
Erenberg A, Leff RD, Haack DG, et al: Caffeine citrate for the treatment of apnea of prematurity: A double-blind, placebo-controlled study. Pharmacotherapy2000;20:644-652.
Anderson BJ, Gunn TR, Holford NHG, et al: Caffeine overdose in a premature infant:
Clinical course and pharmacokinetics. Anaesth Intensive Care1999;27:307-311.
Lane AJP, Coombs RC, Evans DH, et al: Effect of caffeine on neonatal splanchnic blood flow. Arch Dis Child Fetal Neonatal Ed1999;80:F-128-F129.
Lee TC, Charles B, Steer P: Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity. Clin Pharmacol Ther1997;61:628-640.
Falcao AC, Fernandez de Gatta MM, Delgado Iribarnegaray MF, et al: Population pharmacokinetics of caffeine in premature neonates. Eur J Clin
Pharmacol1997;52:211-217.
Zanardo V, Dani C, Trevisanuto D: Methylxanthines increase renal calcium excretion in preterm infants. Biol Neonate 1995;68:169-74.
Product Information, Bedford Laboratories, 2008 Title Caffeine Citrate
Dose
Loading dose: 20 to 25 mg/kg of caffeine citrate IV over 30 minutes or orally.
(Equivalent to 10 to 12.5 mg/kg caffeine base).
Maintenance dose: 5 to 10 mg/kg per dose of caffeine citrate IV slow push or orally every 24 hours. (Equivalent to 2.5 to 5 mg/kg caffeine base).
Maintenance dose should be started 24 hours after the loading dose.
May consider an additional loading dose and higher maintenance doses if able to monitor serum concentrations.
(Please note that emphasis has changed to caffeine citrate due to commercially
available product. This product (Cafcit®) may be administered both intravenously and orally).
Uses
Treatment of neonatal apnea, including post-extubation and post-anesthesia. (More favorable therapeutic index than aminophylline).
Pharmacology
The pharmacological effects of caffeine are mediated by its antagonism of the actions of adenosine at cell surface receptors. It is rapidly distributed in the brain, with CNS levels approximating plasma levels. Caffeine increases the respiratory center output, chemoreceptor sensitivity to CO2, smooth muscle relaxation, and cardiac output.
Oxygen consumption may be increased and weight gain may be reduced. Renal effects include diuresis and increased urinary calcium excretion. Orally administered caffeine citrate is rapidly and completely absorbed. There is almost no first-pass metabolism. In neonates, approximately 86% is excreted unchanged in the urine, with the remainder metabolized via the CYP1A2 enzyme system. The serum half-life of caffeine ranges from 40 to 230 hours, decreasing with advancing postmenstrual age until 60 weeks PMA. Half-life is prolonged in infants with cholestatic hepatitis.
Adverse Effects
Adverse effects are usually mild, and include restlessness, vomiting, and functional cardiac symptoms. There has been a suggested association with NEC, but causality has never been proven. Loading doses of 25 mg/kg caffeine (50 mg/kg caffeine citrate) have been reported to decrease cerebral and intestinal blood flow velocity.
Monitoring
Baseline caffeine levels are recommended in neonates previously treated with theophylline and neonates born to mothers who consumed caffeine prior to delivery.
If using the suggested doses, measuring serum concentrations is probably not
necessary. Monitoring of serum drug concentration should be based on a trough level determined on approximately day 5 of therapy. Therapeutic trough serum concentration is 5 to 25 mcg/mL. Concentrations greater than 40 to 50 mcg/mL are toxic. Assess for agitation. Monitor heart rate; consider withholding dose if greater than 180 beats per minute.
Special Considerations/Preparation
Both Cafcit® Oral Solution and Cafcit® Injection for intravenous administration are preservative free and available in 3-mL single use vials. Each mL of Cafcit® contains 20 mg of caffeine citrate (equivalent to 10 mg caffeine base). Store at room
temperature.
Alternatively, an oral solution may be prepared by dissolving 2.5 g of caffeine anhydrous powder in 250 mL of water, yielding a final concentration of 10 mg/mL.
Solution is stable for 4 weeks refrigerated. Crystals form when stored at low
temperature but dissolve at room temperature without loss of potency. Do not freeze.
Solution Compatibility D5W and D50W.
Terminal Injection Site Compatibility
Dex/AA solutions. Alprostadil, amikacin, aminophylline, calcium gluconate, cefotaxime, cimetidine, clindamycin, dexamethasone, dobutamine, dopamine,
doxapram, epinephrine, fentanyl, gentamicin, heparin (concentration less than or equal to 1 unit/mL), isoproterenol, lidocaine, metoclopramide, morphine, nitroprusside, pancuronium, penicillin G, phenobarbital, sodium bicarbonate, and vancomycin.
Terminal Injection Site Incompatibility
Acyclovir, furosemide, ibuprofen lysine, lorazepam, nitroglycerin, and oxacillin.
References
Schmidt B, Roberts RS, Davis P, et al: Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 2007;357:1893-1902.
Schmidt B, Roberts RS, Davis P, et al: Caffeine therapy for apnea of prematurity. N Engl J Med 2006;354:2112-2121.
Steer P, Flenady V, Shearman A, et al: High dose caffeine citrate for extubation of preterm infants: a randomized controlled trial. Arch Dis Child Fetal Neonatal Ed 2004;89:F499-F503.
Comer AM, Perry CM, Figgitt DP: Caffeine citrate: A review of its use in apnoea of prematurity. Paediatr Drugs 2001;3:61-70.
Bauer J, Maier K, Linderkamp O, Hentschel R: Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea. Pediatrics 2001;107:660-663.
Erenberg A, Leff RD, Haack DG, et al: Caffeine citrate for the treatment of apnea of prematurity: A double-blind, placebo-controlled study. Pharmacotherapy2000;20:644-652.
Anderson BJ, Gunn TR, Holford NHG, et al: Caffeine overdose in a premature infant:
Clinical course and pharmacokinetics. Anaesth Intensive Care1999;27:307-311.
Lane AJP, Coombs RC, Evans DH, et al: Effect of caffeine on neonatal splanchnic blood flow. Arch Dis Child Fetal Neonatal Ed1999;80:F-128-F129.
Lee TC, Charles B, Steer P: Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity. Clin Pharmacol Ther1997;61:628-640.
Falcao AC, Fernandez de Gatta MM, Delgado Iribarnegaray MF, et al: Population pharmacokinetics of caffeine in premature neonates. Eur J Clin
Pharmacol1997;52:211-217.
Zanardo V, Dani C, Trevisanuto D: Methylxanthines increase renal calcium excretion in preterm infants. Biol Neonate 1995;68:169-74.
Product Information, Bedford Laboratories, 2008