Pronunciation:

(KAF een)

U.S. Brand Names:

Synonyms:

Generic Available:

Use:

Caffeine citrate: Treatment of idiopathic apnea of prematurity

Caffeine and sodium benzoate: Treatment of acute respiratory depression (not a preferred agent)

Caffeine [OTC labeling]: Restore mental alertness or wakefulness when experiencing fatigue

Use - Unlabeled/Investigational:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Caffeine citrate should not be interchanged with caffeine and sodium benzoate. Avoid use of products containing sodium benzoate in neonates; has been associated with a potentially fatal toxicity ("gasping syndrome") in neonates, including metabolic acidosis, respiratory distress, gasping respirations, seizures, intracranial hemorrhage, hypotension, and cardiovascular collapse. In vitro and animal studies have shown that benzoate also displaces bilirubin from protein-binding sites. Neonates receiving caffeine citrate should be closely monitored for the development of necrotizing enterocolitis. Caffeine serum levels should be closely monitored to optimize therapy and prevent serious toxicity.

Adverse Reactions:

Cardiovascular: Angina, arrhythmia (ventricular), chest pain, flushing, palpitation, sinus tachycardia, tachycardia (supraventricular), vasodilation

Central nervous system: Agitation, delirium, dizziness, hallucinations, headache, insomnia, irritability, psychosis, restlessness

Dermatologic: Urticaria

Gastrointestinal: Esophageal sphincter tone decreased, gastritis

Neuromuscular & skeletal: Fasciculations

Ocular: Intraocular pressure increased (>180 mg caffeine), miosis

Renal: Diuresis

Overdosage/Toxicology:

Drug Interactions:

Benzodiazepines: Caffeine may diminish the sedative or anxiolytic effects of benzodiazepines.

CYP1A2 inducers: May decrease the levels/effects of caffeine. Example inducers include aminoglutethimide, carbamazepine, phenobarbital, and rifampin.

CYP1A2 inhibitors: May increase the levels/effects of caffeine. Example inhibitors include amiodarone, fluvoxamine, ketoconazole, and rofecoxib.

Quinolone antibiotics (specifically ciprofloxacin, norfloxacin, ofloxacin): May increase the levels/effects of caffeine.

Stability:

Caffeine citrate: Injection and oral solution contain no preservatives; injection is chemically stable for at least 24 hours at room temperature when diluted to 10 mg/mL (as caffeine citrate) with D5W, D50W, Intralipid® 20%, and Aminosyn® 8.5%; also compatible with dopamine (600 mcg/mL), calcium gluconate 10%, heparin (1 unit/mL), and fentanyl (10 mcg/mL) at room temperature for 24 hours.

Compatibility:

Stable in D5W, D50W, Intralipid® 20%, Aminosyn® 8.5%

Compatible: Calcium gluconate 10%, dopamine (600 mcg/mL), fentanyl (10 mcg/mL), heparin (1 unit/mL)

Mechanism of Action:

Pharmacodynamics/Kinetics:

Distribution: Vd:

Neonates: 0.8-0.9 L/kg

Children >9 months to Adults: 0.6 L/kg

Protein binding: 17% (children) to 36% (adults)

Metabolism: Hepatic, via demethylation by CYP1A2. Note: In neonates, interconversion between caffeine and theophylline has been reported (caffeine levels are ~25% of measured theophylline after theophylline administration and ~3% to 8% of caffeine would be expected to be converted to theophylline)

Half-life elimination:

Neonates: 72-96 hours (range: 40-230 hours)

Children >9 months and Adults: 5 hours

Time to peak, serum: Oral: Within 30 minutes to 2 hours

Excretion:

Neonates month: 86% excreted unchanged in urine

Infants >1 month and Adults: In urine, as metabolites

Dosage:

Note:Caffeine citrate should not be interchanged with the caffeine sodium benzoate formulation.

Caffeine citrate: Neonates: Apnea of prematurity: Oral, I.V.:

Loading dose: 10-20 mg/kg as caffeine citrate (5-10 mg/kg as caffeine base). If theophylline has been administered to the patient within the previous 3 days, a full or modified loading dose (50% to 75% of a loading dose) may be given.

Maintenance dose: 5 mg/kg/day as caffeine citrate (2.5 mg/kg/day as caffeine base) once daily starting 24 hours after the loading dose. Maintenance dose is adjusted based on patient's response and serum caffeine concentrations.

Caffeine and sodium benzoate:

Children: Stimulant: I.M., I.V., SubQ: 8 mg/kg every 4 hours as needed

Children 12 years and Adults: OTC labeling (stimulant): Oral: 100-200 mg every 3-4 hours as needed

Adults:

Respiratory depression: I.M., I.V.: 250 mg as a single dose; may repeat as needed. Maximum single dose should be limited to 500 mg; maximum amount in any 24-hour period should generally be limited to 2500 mg

Spinal puncture headache (unlabeled use):

I.V.: 500 mg in 1000 mL NS infused over 1 hour, followed by 1000 mL NS infused over 1 hour; a second course of caffeine can be given for unrelieved headache pain in 4 hours.

Oral: 300 mg as a single dose

Stimulant/diuretic (unlabeled use): I.M., I.V.: 500 mg, maximum single dose: 1 g

Dosage adjustment in renal impairment: No dosage adjustment required.

Administration:

Oral: May be administered without regard to feedings or meals; may administer injectable formulation (caffeine citrate) orally

Parenteral:

Caffeine citrate: Infuse loading dose over at least 30 minutes; maintenance dose may be infused over at least 10 minutes; may administer without dilution or diluted with D5W to 10 mg caffeine citrate/mL

Caffeine and sodium benzoate: I.V. as slow direct injection; for spinal headaches, dilute in 1000 mL NS and infuse over 1 hour; follow with 1000 mL NS, infuse over 1 hour; may administer I.M. undiluted

Reference Range:

Therapeutic: Apnea of prematurity: 8-20 mcg/mL

Potentially toxic: >20 mcg/mL

Toxic: >50 mcg/mL

Patient Education:

Anesthesia and Critical Care Concerns/Other Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

Caplet (Caffedrine®, Vivarin®): 200 mg [OTC]

Injection, solution, as citrate [preservative free] (Cafcit®): 20 mg/mL (3 mL) [equivalent to 10 mg/mL caffeine base]

Injection, solution [with sodium benzoate]: Caffeine 125 mg/mL and sodium benzoate 125 mg/mL (2 mL); caffeine 121 mg/mL and sodium benzoate 129 mg/mL (2 mL)

Lozenge: 75 mg [OTC; Hazelnut coffee or mochamint flavor]

Solution, oral, as citrate (Cafcit®): 20 mg/mL (3 mL) [equivalent to 10 mg/mL caffeine base]

Tablet:

Lucidex: 100 mg [OTC]

NoDoz® Maximum Strength, Vivarin®: 200 mg [OTC]

International Brand Names: