Caffeine CitrateInjection, USP

Caffeine Citrate Injection, USP

For Intravenous Administration

INDICATIONS AND USAGE
Caffeine citrate injection is indicated for the treatment of apnea of prematurity.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Caffeine citrate injection is contraindicated in patients who have demonstrated hypersensitivity to any of its components.

WARNINGS
Necrotizing Enterocolitis
During the double-blind, placebo-controlled clinical trial, 6 cases of necrotizing enterocolitis developed among the 85 infants studied (caffeine=46, placebo=39), with 3 cases resulting in death. Five of the 6 patients with necrotizing enterocolitis were randomized to or had been exposed to caffeine citrate.
Reports in the published literature have not established a causal relationship. As with all preterm infants, patients being treated with caffeine citrate should be carefully monitored for the development of necrotizing enterocolitis.

PRECAUTIONS
General
Apnea of prematurity is a diagnosis of exclusion. Other causes of apnea should be ruled out or properly treated prior to initiation of caffeine citrate.

Caffeine is a central nervous system stimulant and in cases of caffeine overdose, seizures have been reported. Caffeine citrate should be used with caution in infants with seizure disorders.
The duration of treatment of apnea of prematurity in the placebo-controlled trial was limited to 10 to 12 days. The efficacy of Caffeine Citrate for longer periods of treatment has not been established. Safety and efficacy of Caffeine Citrate for use in the prophylactic treatment of sudden infant death syndrome (SIDS) or prior to extubation in mechanically ventilated infants have also not been established.

Cardiovascular
Caffeine has been shown to increase heart rate, left ventricular output, and stroke volume in published studies. Therefore, caffeine citrate should be used with caution in infants with cardiovascular disease.

Renal and Hepatic Systems
Caffeine citrate should be administered with caution in infants with impaired renal or hepatic function. Serum concentrations of caffeine should be monitored and dose administration of caffeine citrate should be adjusted to avoid toxicity.

Laboratory Tests
Prior to initiation of caffeine citrate, baseline serum levels of caffeine should be measured in infants previously treated with theophylline. Serious toxicity has been reported in the literature when serum caffeine levels exceed 50 mg/L. Serum concentrations of caffeine may need to be monitored periodically throughout treatment to avoid toxicity.

In clinical studies reported in the literature, cases of hypoglycemia and hyperglycemia have been observed. Therefore, serum glucose may need to be periodically monitored in infants receiving caffeine citrate.

Drug Interactions
Few data exist on drug interactions with caffeine in preterm neonates. Interconversion between caffeine and theophylline has been reported. The concurrent use of these drugs is not recommended.

ADVERSE REACTIONS
The following adverse events occurred in the double-blind period of the controlled trial
and were more frequent in caffeine citrate (N=46) treated patients than placebo (N=39): 8.7% feeding intolerance; 8.7% rash; 4.3% sepsis; 4.3% necrotizing enterocolitis; 2.2% accidental injury; 2.2% hemorrhage; 2.2% gastritis; 2.2% gastrointestinal hemorrhage; 2.2% disseminated intravascular coagulation; 2.2% acidosis; 2.2% healing abnormal; 2.2% cerebral hemorrhage; 2.2% dyspnea; 2.2% lung edema; 2.2% dry skin; 2.2% skin breakdown; 2.2% retinopathy of prematurity; 2.2% kidney failure. See WARNINGS.

OVERDOSAGE
Following overdose, serious toxicity has been associated with caffeine citrate.

Dosage and Administration
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).

For additional Safety Information, please see Full Prescribing Information.

You are encouraged to report adverse drug events to American Regent Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

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