Caffeine Citrate (2 brand names, 1 dosage form, 2 routes)
Available dosage forms: SOLUTION.
Routes of administration: ORAL, INTRAVENOUS.
Brand Names
- CAFCIT
- CAFFEINE CITRATE
Related Health Topics
Indications and Usage
Caffeine citrate injection is indicated for the treatment of apnea of prematurity.
Dosage and Administration
Prior to initiation of caffeine citrate, baseline serum levels of caffeine should be measured in infants previously treated with theophylline, since preterm infants metabolize theophylline to caffeine. Likewise, baseline serum levels of caffeine should be measured in infants born to mothers who consumed caffeine prior to delivery, since caffeine readily crosses the placenta. The recommended loading dose and maintenance doses of caffeine citrate follow. Dose of caffeine citrate Volume Dose of caffeine citrate mg/kg Route Frequency Loading Dose 1 mL/kg 20 mg/kg Intravenous* (over 30 minutes) One Time Maintenance Dose 0.25 mL/kg 5 mg/kg Intravenous* (over 10 minutes) or Orally Every 24 hours** *Using a syringe infusion pump **Beginning 24 hours after the loading dose NOTE THAT THE DOSE OF CAFFEINE BASE IS ONE-HALF THE DOSE WHEN EXPRESSED AS CAFFEINE CITRATE (e.g., 20 mg of caffeine citrate is equivalent to 10 mg of caffeine base). Serum concentrations of caffeine may need to be monitored periodically throughout treatment to avoid toxicity. Serious toxicity has been associated with serum levels greater than 50 mg/L. Caffeine citrate should be inspected visually for particulate matter and discoloration prior to administration. Vials containing discolored solution or visible particulate matter should be discarded. Drug Compatibility To test for drug compatibility with common intravenous solutions or medications, 20 mL of caffeine citrate injection were combined with 20 mL of a solution or medication, with the exception of an Intralipid ®admixture, which was combined as 80 mL/80 mL. The physical appearance of the combined solutions was evaluated for precipitation. The admixtures were mixed for 10 minutes and then assayed for caffeine. The admixtures were then continually mixed for 24 hours, with further sampling for caffeine assays at 2, 4, 8, and 24 hours. Based on this testing, caffeine citrate injection USP, 60 mg/3 mL is chemically stable for 24 hours at room temperatu
Contraindications
Caffeine citrate injection is contraindicated in patients who have demonstrated hypersensitivity to any of its components.
Adverse Reactions
Overall, the reported number of adverse events in the double-blind period of the controlled trial was similar for the caffeine citrate and placebo groups. The following table shows adverse events that occurred in the double-blind period of the controlled trial and that were more frequent in caffeine citrate-treated patients than placebo. ADVERSE EVENTS THAT OCCURRED MORE FREQUENTLY IN CAFFEINE CITRATE INJECTION-TREATED PATIENTS THAN PLACEBO DURING DOUBLE-BLIND THERAPY Adverse Event (AE) Caffeine citrate N=46 n (%) Placebo N=39 n (%) BODY AS A WHOLE Accidental Injury 1 (2.2) 0 (0.0) Feeding Intolerance 4 (8.7) 2 (5.1) Sepsis 2 (4.3) 0 (0.0) CARDIOVASCULAR SYSTEM Hemorrhage 1 (2.2) 0 (0.0) DIGESTIVE SYSTEM Necrotizing Enterocolitis 2 (4.3) 1 (2.6) Gastritis 1 (2.2) 0 (0.0) Gastrointestinal Hemorrhage 1 (2.2) 0 (0.0) HEMIC AND LYMPHATIC SYSTEM Disseminated Intravascular Coagulation 1 (2.2) 0 (0.0) METABOLIC AND NUTRITIVE DISORDERS Acidosis 1 (2.2) 0 (0.0) Healing Abnormal 1 (2.2) 0 (0.0) NERVOUS SYSTEM Cerebral Hemorrhage 1 (2.2) 0 (0.0) RESPIRATORY SYSTEM Dyspnea 1 (2.2) 0 (0.0) Lung Edema 1 (2.2) 0 (0.0) SKIN AND APPENDAGES Dry Skin 1 (2.2) 0 (0.0) Rash 4 (8.7) 3 (7.7) Skin Breakdown 1 (2.2) 0 (0.0) SPECIAL SENSES Retinopathy of Prematurity 1 (2.2) 0 (0.0) UROGENITAL SYSTEM Kidney Failure 1 (2.2) 0 (0.0) In addition to the cases above, three cases of necrotizing enterocolitis were diagnosed in patients receiving caffeine citrate during the open-label phase of the study. Three of the infants who developed necrotizing enterocolitis during the trial died. All had been exposed to caffeine. Two were randomized to caffeine, and one placebo patient was “rescued” with open-label caffeine for uncontrolled apnea. Adverse events described in the published literature include: central nervous system stimulation (i.e., irritability, restlessness, jitteriness), cardiovascular effects (i.e., tachycardia, increased left ventricular output, and increased stroke volume), gastrointestin
Drug Interactions
Cytochrome P450 1A2 (CYP1A2) is known to be the major enzyme involved in the metabolism of caffeine. Therefore, caffeine has the potential to interact with drugs that are substrates for CYP1A2, inhibit CYP1A2, or induce CYP1A2. Few data exist on drug interactions with caffeine in preterm neonates. Based on adult data, lower doses of caffeine may be needed following coadministration of drugs which are reported to decrease caffeine elimination (e.g., cimetidine and ketoconazole) and higher caffeine doses may be needed following coadministration of drugs that increase caffeine elimination (e.g., phenobarbital and phenytoin). Caffeine administered concurrently with ketoprofen reduced the urine volume in four healthy volunteers. The clinical significance of this interaction in preterm neonates is not known. Interconversion between caffeine and theophylline has been reported in preterm neonates. The concurrent use of these drugs is not recommended.
Overdosage
Following overdose, serum caffeine levels have ranged from approximately 24 mg/L (a postmarketing spontaneous case report in which an infant exhibited irritability, poor feeding, and insomnia) to 350 mg/L. Serious toxicity has been associated with serum levels greater than 50 mg/L (see PRECAUTIONS , Laboratory Tests and DOSAGE AND ADMINISTRATION ). Signs and symptoms reported in the literature after caffeine overdose in preterm infants include fever, tachypnea, jitteriness, insomnia, fine tremor of the extremities, hypertonia, opisthotonos, tonic-clonic movements, nonpurposeful jaw and lip movements, vomiting, hyperglycemia, elevated blood urea nitrogen, and elevated total leukocyte concentration. Seizures have also been reported in cases of overdose. One case of caffeine overdose complicated by development of intraventricular hemorrhage and long-term neurological sequelae has been reported. Another case of caffeine citrate overdose (from New Zealand); not caffeine citrate of an estimated 600 mg caffeine citrate (approximately 322 mg/kg) administered over 40 minutes was complicated by tachycardia, ST depression, respiratory distress, heart failure, gastric distention, acidosis, and a severe extravasation burn with tissue necrosis at the peripheral intravenous injection site. No deaths associated with caffeine overdose have been reported in preterm infants. Treatment of caffeine overdose is primarily symptomatic and supportive. Caffeine levels have been shown to decrease after exchange transfusions. Convulsions may be treated with intravenous administration of diazepam or a barbiturate such as pentobarbital sodium.