Version July 2025
Apnea of prematurity: Caffeine citrate: Note: Dose expressed as caffeine citrate; caffeine base is 1/2 the dose of the caffeine citrate:
Manufacturer's labeling: Preterm neonates:
Loading dose: IV: 20 mg/kg caffeine citrate as a one-time dose.
Maintenance dose: Oral, IV: 5 mg/kg/dose caffeine citrate once daily, beginning 24 hours after loading dose.
Alternate dosing: GA <32 weeks:
Loading dose: IV: 20 to 40 mg/kg caffeine citrate (Ref); loading doses as high as 80 mg/kg of caffeine citrate have been reported (Ref), but should be utilized with caution (See Note).
Maintenance dose: Oral, IV: 5 to 20 mg/kg/dose caffeine citrate once daily starting 24 hours after the loading dose (Ref).
Note: Higher doses (Load: 40 mg/kg and 80 mg/kg; maintenance dose: 20 mg/kg/dose) were shown to significantly decrease the incidence of apnea, need for oxygen therapy, and extubation failures; incidence of tachycardia was conflicting with one study showing an increased incidence with higher doses compared to low dose (23% vs 8%) while the other showed no significant difference between low and high dose (Ref). Loading doses of 80 mg/kg must be used with caution; one study evaluating the prophylactic use of high-dose caffeine (total dose of 80 mg/kg over 36 hours) compared to standard dose showed patients in the high-dose group had a higher incidence of cerebellar hemorrhage (36% vs 10%) along with increased tone and abnormal movements (Ref); although not statistically significant, these patients also trended towards a higher incidence of seizures and increased EEG measured seizure duration over the first 72 hours; however, there was no difference in the number of clinical seizures requiring treatment, status epilepticus, IVH, hypoglycemia, or perinatal hypoxic ischemia between the 2 groups (Ref).
Dosing: Altered Kidney Function: Neonatal: Preterm Neonates: Use with caution with impaired renal function; monitor serum concentrations and adjust dose to avoid toxicity; has not been studied.
Dosing: Altered Liver Function: Neonatal: Preterm Neonates: Use with caution with impaired hepatic function; monitor serum concentrations and adjust dose to avoid toxicity; has not been studied.
Note: Caffeine citrate should not be interchanged with the caffeine sodium benzoate formulation. Caffeine and sodium benzoate dosing presented as the combination (caffeine base amount is 50% of the caffeine and sodium benzoate combination).
Stimulant: OTC labeling: Caffeine (base): Children ≥12 years and Adolescents: Oral: 100 to 200 mg every 3 to 4 hours as needed
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
(For additional information see "Caffeine: Drug information")
Note: Caffeine citrate should not be interchanged with the caffeine sodium benzoate formulation. Dosing presented as the combination of caffeine and sodium benzoate unless otherwise noted (caffeine base amount is 50% of the caffeine and sodium benzoate combination).
Augmentation of seizure induction during electroconvulsive therapy (ECT) (off-label use): IV: Initial: 500 to 1,000 mg caffeine and sodium benzoate (equivalent to 250 to 500 mg caffeine base); if necessary during subsequent ECT sessions, may titrate dose up or down in increments of 250 to 500 mg caffeine and sodium benzoate (equivalent to 125 to 250 mg caffeine base); a maximum dose of 2,000 mg caffeine and sodium benzoate (equivalent to 1,000 mg caffeine base) during an ECT session has been reported (Ref).
Postdural puncture headache (off-label use): Oral: 300 mg (caffeine base) as a single dose (Ref).
Reversal of dipyridamole- or regadenoson-induced adverse reactions (eg, angina, hypotension) during nuclear cardiac stress testing (alternative agent) (off-label use): Caffeine citrate: IV: 60 mg (diluted in 25 mL of D5W) over 3 to 5 minutes (Ref).
Stimulant: OTC labeling: Oral: 200 mg (caffeine base) every 3 to 4 hours as needed.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution.
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are for the IV formulation in preterm infants.
1% to 10%:
Dermatologic: Epidermal thinning, skin rash, xeroderma
Endocrine & metabolic: Acidosis
Gastrointestinal: Gastritis, gastrointestinal hemorrhage
Hematologic & oncologic: Disseminated intravascular coagulation, hemorrhage
Infection: Sepsis
Nervous system: Cerebral hemorrhage
Ophthalmic: Retinopathy of prematurity
Renal: Kidney failure
Respiratory: Dyspnea, pulmonary edema
Miscellaneous: Abnormal healing, reduced intake of food/liquids (feeding intolerance)
Frequency not defined: Gastrointestinal: Necrotizing enterocolitis
Postmarketing:
Cardiovascular: Cardiac disorder (including increased left ventricular output, increased stroke volume, tachycardia)
Endocrine & metabolic: Hyperglycemia, hypoglycemia
Gastrointestinal: Gastrointestinal disease (including increased gastric aspirate, gastrointestinal intolerance)
Genitourinary: Increased urine output
Nervous system: Central nervous system stimulation (including irritability, jitteriness, restlessness)
Renal: Increased creatinine clearance, increased urinary sodium, increased urine calcium excretion
Hypersensitivity to caffeine or any component of the formulation; sodium benzoate is not for use in neonates.
OTC labeling: When used for self-medication, do not use in children <12 years of age or as a substitute for sleep.
Disease-related concerns:
• Anxiety: Avoid use in patients with anxiety, agitation, or tremor.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease; avoid use in patients with symptomatic cardiac arrhythmias.
• Gastrointestinal disease: Use with caution in patients with a history of peptic ulcer and/or gastroesophageal reflux.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; may lower seizure threshold leading to new onset or breakthrough seizure activity.
Special populations:
• Neonates: Caffeine citrate should be closely monitored for the development of necrotizing enterocolitis in the neonate; caffeine serum levels should be closely monitored to optimize therapy and prevent serious toxicity. 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.
Dosage form specific issues:
• Product interchangeability: Caffeine citrate should not be interchanged with caffeine and sodium benzoate.
Other warnings and precautions:
• Self-medication (OTC use): OTC products contain 200 mg of caffeine per tablet, approximately the amount of caffeine similar to 1 cup of coffee. When used for self-medication (OTC), limit the use of caffeine containing medications, foods, or beverages; too much caffeine may cause irritability, nervousness, sleeplessness, and tachycardia. Discontinue use and contact health care provider if drowsiness or fatigue are persistent or recur.
• Transcutaneous electrical nerve stimulation: Analgesia from transcutaneous electrical nerve stimulation may be lessened with concomitant caffeine use (Marchand 1995).
During a caffeine citrate double-blind, placebo-controlled study, 6 of 85 patients developed necrotizing enterocolitis (NEC) with 3 cases resulting in death; 5 of these 6 patients had received caffeine citrate. In a large randomized, placebo-controlled trial which compared caffeine citrate to placebo in ~2,000 patients with apnea of prematurity, the incidence of NEC was similar between the caffeine group and placebo group (6.3% vs 6.7%) (Schmidt 2006). Although no causal relationship has been established, neonates who receive caffeine citrate should be closely monitored for the development of NEC. Caffeine serum levels should be closely monitored to optimize therapy and prevent serious toxicity.
The incidence of cerebellar hemorrhage was shown to be increased in patients receiving high-dose caffeine citrate (80 mg/kg total load over 36 hours) compared to those receiving standard doses (36% vs 10%) in a randomized, controlled trial in preterm neonates (n=74; GA ≤30 weeks; PNA ≤24 hours); in addition, this group also had subtle neurobehavioral differences including increased tone and abnormal movements at term equivalent age (McPherson 2015). In a post hoc analysis of this same group of neonates the high-dose group also trended towards a higher incidence of seizures (40% vs 58%; p = 0.1) and an increase in seizure duration (48.9 vs 170.9 seconds; p = 0.1) as indicated by continuous limited channel aEEG monitoring over the first 72 hours of life, although this was not statistically significant. No difference in the number of clinical seizures requiring treatment or status epilepticus were noted between the groups; also no difference in the rates of IVH, hypoglycemia or perinatal hypoxic ischemia were noted (Vesoulis 2016). Authors noted that these adverse effects discouraged the potential for a larger trial; if use deemed necessary, close monitoring is recommended (McPherson 2015; Vesoulis 2016). In a large randomized, placebo-controlled trial which compared caffeine citrate (load: 20 mg/kg; maintenance: 5 to 10 mg/kg/dose) to placebo in ~2,000 patients (birthweight: 500 to 1,250 g; GA: mean: 27 weeks) with apnea of prematurity, the incidence of brain injury as evidenced by ultrasound and death were similar between the caffeine citrate and placebo groups. Long-term follow up at both 18 months and 5 years corrected age again showed no difference in death or adverse neurodevelopmental outcomes between the 2 groups (Schmidt 2006; Schmidt 2007; Schmidt 2012).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution, as citrate [preservative free]:
Cafcit: 60 mg/3 mL (3 mL) [equivalent to 10 mg/mL caffeine base]
Generic: 60 mg/3 mL (3 mL) [equivalent to 10 mg/mL caffeine base]
Injection, solution [with sodium benzoate]:
Generic: Caffeine 125 mg/mL and sodium benzoate 125 mg/mL (2 mL)
Solution, oral, as citrate [preservative free]:
Cafcit: 60 mg/3 mL (3 mL) [equivalent to 10 mg/mL caffeine base] [DSC]
Generic: 60 mg/3 mL (3 mL) [equivalent to 10 mg/mL caffeine base]
Tablet, oral:
Keep Alert: 200 mg
FT Stay Awake: 200 mg
Stay Awake: 200 mg
Stay Awake Maximum Strength: 200 mg
Vivarin: 200 mg
Generic: 200 mg
Yes: Tablet, caffeine and sodium benzoate injection, injection, oral solution
Solution (Caffeine Citrate Intravenous)
60 mg/3 mL (per mL): $2.11 - $14.00
Solution (Caffeine Citrate Oral)
60 mg/3 mL (per mL): $4.80 - $9.60
Solution (Caffeine-Sodium Benzoate Injection)
125-125 mg/mL (per mL): $21.91
Tablets (Caffeine Oral)
200 mg (per each): $0.11
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Infusion, solution, as citrate [preservative free]:
Peyona: 20 mg/mL (1 mL)
Solution, oral, as citrate [preservative free]:
Peyona: 20 mg/mL (1 mL)
Note: A caffeine citrate oral solution (20 mg/mL) is commercially available.
10 mg/mL Oral Solution
A 10 mg/mL oral solution of caffeine (as citrate) may be prepared from 10 g citrated caffeine powder combined with 10 g citric acid USP and dissolved in 1000 mL distilled water. Label “shake well”. Stable for 3 months at room temperature (Nahata 2014).
20 mg/mL Oral Solution
A 20 mg/mL oral solution of caffeine (as citrate) may be made from 10 g citrated caffeine powder and dissolved in 250 mL sterile water for irrigation. Stir solution until completely clear, then add a 2:1 mixture of simple syrup and cherry syrup in sufficient quantity to make 500 mL. Label "shake well" and "refrigerate". Stable for 90 days (Eisenberg 1984).
Oral: May be administered without regard to feedings or meals.
Parenteral: Caffeine citrate: IV: May administer undiluted or further diluted with D5W. Infuse loading dose over at least 30 minutes; maintenance dose may be infused over at least 10 minutes.
Oral: May be administered without regard to feedings or meals. May administer injectable formulation (caffeine citrate) orally.
Parenteral:
Caffeine citrate: Reversal of dipyridamole- or regadenoson-induced adverse reactions during cardiac stress testing: Infuse dose (diluted in 25 mL D5W) over 3 to 5 minutes (Ref).
Caffeine and sodium benzoate: Note: Use a 0.22 micron in-line filter when administering (Ref).
Direct IV injection: Administer slowly.
Store at 20°C to 25°C (68°F to 77°F).
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.
Caffeine citrate: Treatment of apnea of prematurity (FDA approved in preterm neonates).
Caffeine (base): Restore mental alertness or wakefulness when experiencing fatigue (OTC Product: FDA approved in ages ≥12 years and adults).
Caffeine and sodium benzoate: Treatment (in conjunction with supportive measures) of acute respiratory depression associated with overdose of CNS depressant drugs (not a preferred agent) (FDA approved in adults); has also been used for treatment of postdural puncture headaches.
Substrate of CYP1A2 (Major), CYP2C9 (Minor), CYP2D6 (Minor), CYP2E1 (Minor), CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acebrophylline: May increase stimulatory effects of CNS Stimulants. Risk X: Avoid
Adenosine: Caffeine and Caffeine Containing Products may decrease therapeutic effects of Adenosine. Management: Monitor for decreased effect of adenosine if patient is receiving caffeine; significantly higher adenosine doses or alternative agents may be required. Discontinue caffeine 24 hours in advance of scheduled diagnostic use of adenosine if possible. Risk D: Consider Therapy Modification
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bornaprine: Sympathomimetics may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Broccoli: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor
Bromperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Bromperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Bromperidol: Caffeine and Caffeine Containing Products may decrease absorption of Bromperidol. Risk C: Monitor
BuPROPion: May increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor
Cannabinoid-Containing Products: May increase tachycardic effects of Sympathomimetics. Risk C: Monitor
Cannabis: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: CYP1A2 Inhibitors (Weak) may increase serum concentration of CloZAPine. Risk C: Monitor
Cocaine (Topical): May increase hypertensive effects of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider Therapy Modification
CYP1A2 Inducers (Moderate): May decrease serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
CYP1A2 Inhibitors (Moderate): May increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
CYP1A2 Inhibitors (Strong): May increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
Diazoxide Choline: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid
Dihydralazine: Sympathomimetics may decrease therapeutic effects of Dihydralazine. Risk C: Monitor
Doxofylline: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Doxofylline. Risk X: Avoid
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Esketamine (Injection): May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for elevated heart rate, hypertension, and arrhythmias may be increased. Risk C: Monitor
Esketamine (Nasal): May increase hypertensive effects of CNS Stimulants. Risk C: Monitor
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Formoterol: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Formoterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Formoterol. Risk C: Monitor
Guanethidine: May increase hypertensive effects of Sympathomimetics. Guanethidine may increase arrhythmogenic effects of Sympathomimetics. Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Indacaterol: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Indacaterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Indacaterol. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid
Landiolol: Sympathomimetics may decrease therapeutic effects of Landiolol. Risk C: Monitor
Levothyroxine: May increase therapeutic effects of Sympathomimetics. Sympathomimetics may increase therapeutic effects of Levothyroxine. Levothyroxine may increase adverse/toxic effects of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Risk C: Monitor
Linezolid: May increase hypertensive effects of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider Therapy Modification
Lithium: Caffeine and Caffeine Containing Products may decrease serum concentration of Lithium. Risk C: Monitor
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
MigALAstat: Caffeine and Caffeine Containing Products may decrease serum concentration of MigALAstat. Risk X: Avoid
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Norfloxacin: May increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Olodaterol: Caffeine and Caffeine Containing Products may increase adverse/toxic effects of Olodaterol. Caffeine and Caffeine Containing Products may increase hypokalemic effects of Olodaterol. Risk C: Monitor
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Pipemidic Acid: May increase serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Primaquine: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Regadenoson: Caffeine and Caffeine Containing Products may decrease vasodilatory effects of Regadenoson. Management: Avoid use of caffeine and caffeine-containing products for at least 12 hours prior to regadenoson administration. Risk D: Consider Therapy Modification
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Solriamfetol: CNS Stimulants may increase hypertensive effects of Solriamfetol. CNS Stimulants may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Solriamfetol: Sympathomimetics may increase hypertensive effects of Solriamfetol. Sympathomimetics may increase tachycardic effects of Solriamfetol. Risk C: Monitor
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sympathomimetics: May increase adverse/toxic effects of Sympathomimetics. Risk C: Monitor
Tedizolid: May increase adverse/toxic effects of Sympathomimetics. Specifically, the risk for increased blood pressure and heart rate may be increased. Risk C: Monitor
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase serum concentration of Theophylline Derivatives. Risk C: Monitor
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
TiZANidine: CYP1A2 Inhibitors (Weak) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
Tobacco (Smoked): May decrease serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Warfarin: Caffeine and Caffeine Containing Products may decrease anticoagulant effects of Warfarin. Risk C: Monitor
Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Caffeine crosses the placenta; serum concentrations in the fetus are similar to those in the mother (Grosso 2005).
Based on current studies, usual dietary exposure to caffeine is unlikely to cause congenital malformations (Brent 2011). However, available data show conflicting results related to maternal caffeine use and the risk of other adverse events, such as spontaneous abortion or growth retardation (Brent 2011; Jahanfar 2013; Nehlig 1994). Chronic maternal consumption of high amounts of caffeine during pregnancy may lead to neonatal withdrawal at delivery (eg, apnea, irritability, jitteriness, vomiting) (Martin 2007).
The half-life of caffeine is prolonged during the second and third trimesters of pregnancy and maternal and fetal exposure is also influenced by maternal tobacco or alcohol consumption (Brent 2011; Koren 2000). Current guidelines recommend limiting caffeine intake from all sources to ≤200 mg/day during pregnancy (ACOG 2010).
Apnea of prematurity: Heart rate, number and severity of apnea spells, serum caffeine concentration (as appropriate)
Stimulant: Insomnia, tachycardia
Therapeutic: Apnea of prematurity: 8 to 20 mcg/mL (SI: 41.2 to 103 micromole/L)
Potentially toxic: >20 mcg/mL (SI: >103 micromole/L)
Toxic: >50 mcg/mL (SI: >257.5 micromole/L)
Increases levels of 3'5' cyclic AMP by inhibiting phosphodiesterase; CNS stimulant which increases medullary respiratory center sensitivity to carbon dioxide, stimulates central inspiratory drive, and improves skeletal muscle contraction (diaphragmatic contractility); prevention of apnea may occur by competitive inhibition of adenosine
Distribution: Vd:
Neonates: 0.8 to 0.9 L/kg.
Adults: 0.6 L/kg.
Protein binding: 36%.
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 to 96 hours.
Infants ≥9 months, Children, Adolescents, and Adults: 5 hours.
Time to peak, serum: Preterm neonates: Oral: 30 minutes to 2 hours.
Excretion:
Neonates: Urine (86% unchanged).
Infants ≥9 months, Children, Adolescents, and Adults: Urine (1% unchanged).
Pregnancy and cirrhosis: Half-life is increased.
