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Caffeine: Drug information

Caffeine: Drug information
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For additional information see "Caffeine: Patient drug information" and "Caffeine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Cafcit;
  • FT Stay Awake [OTC];
  • Keep Alert [OTC];
  • Stay Awake Maximum Strength [OTC];
  • Stay Awake [OTC];
  • Vivarin [OTC]
Brand Names: Canada
  • Peyona
Pharmacologic Category
  • Central Nervous System Stimulant;
  • Phosphodiesterase Enzyme Inhibitor, Nonselective
Dosing: Adult

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

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

Postdural puncture headache (off-label use): Oral: 300 mg (caffeine base) as a single dose (Ref).

Reversal of dipyridamole- or regadenoson-induced adverse reactions during nuclear cardiac stress testing

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

Stimulant: OTC labeling: Oral: 200 mg (caffeine base) every 3 to 4 hours as needed.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Use with caution.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Use with caution.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Caffeine: Pediatric drug information")

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

Stimulant: OTC labeling: Caffeine (base): Children ≥12 years and Adolescents: Oral: 100 to 200 mg every 3 to 4 hours as needed

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Adverse Reactions

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

Contraindications

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.

Warnings/Precautions

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).

Warnings: Additional Pediatric Considerations

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).

Dosage Forms: US

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

Generic Equivalent Available: US

Yes: Tablet, caffeine and sodium benzoate injection, injection, oral solution

Pricing: US

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

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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)

Administration: Adult

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.

Administration: Pediatric

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.

Use: Labeled Indications

Caffeine citrate: Treatment of apnea of prematurity.

Caffeine and sodium benzoate: See Off-Label uses.

Caffeine [OTC labeling]: Helps restore mental alertness or wakefulness when experiencing drowsiness or fatigue.

Use: Off-Label: Adult

Augmentation of seizure induction during electroconvulsive therapy (caffeine and sodium benzoate); Postdural puncture headache (caffeine base); Reversal of dipyridamole- or regadenoson-induced adverse reactions (eg, angina, hypotension) during nuclear cardiac stress testing (caffeine citrate) (alternative agent)

Metabolism/Transport Effects

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);

Drug Interactions

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.

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

Pregnancy Considerations

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).

Breastfeeding Considerations

Caffeine and its metabolites are present in breast milk (Berlin 1981; Hildebrandt 1983; Martin 2007; Oo 1995; Ryu 1985a).

Actual breast milk concentrations vary widely. The source of caffeine, how caffeinated beverages are brewed, the amount ingested, and the postpartum age of the mother affect concentrations in breast milk (Berlin 1984; Davanzo 2014; Ryu 1985b; Staychansky 1998; Tyrala 1979)

Breast milk concentrations are dependent upon maternal intake from all sources and ability to metabolize caffeine (eg, smoker versus nonsmoker) (Brent 2011). Peak breast milk concentrations generally occur within 1 to 2 hours (Berlin 1984; Calvaresi 2016; Nehlig 1994; Stavchansky 1988). In one study, caffeine was not detected in the breast milk of women ingesting <100 mg (Berlin 1984). Caffeine can be detected in the saliva and serum of some breastfed infants (Hildebrandt 1983; Ryu 1985a). The ability of the breastfeeding child to metabolize caffeine is age-dependent and higher serum concentrations are found in preterm infants (Atkinson 1988; Hildebrant 1983).

Maternal caffeine ingestion may decrease iron concentrations of breast milk (Nehlig 1994). Irritability and jitteriness have been reported in the breastfeeding infant following larger than acceptable amounts of maternal caffeine ingestion (Clement 1989; Rustin 1989). Infant heart rates and sleep patterns were not found to be affected in normal, full-term infants exposed to lesser amounts of caffeine (Ryu 1985b) or older infants (Santos 2012). Long-term effects on infant exposure have not been evaluated (O'Connor 2016).

Moderate amounts of caffeine are considered acceptable with breastfeeding (Ito 2000). Ingestion of <300 mg/day is recommended (O'Connor 2016). Caution is recommended if breastfeeding premature infants, infants small for gestational age, or if exposure to unusually high amounts of caffeine occurs (Atkinson 1988; Nehlig 1994). When maternal caffeine is from dietary sources (eg, coffee), maternal ingestion right after breastfeeding may minimize infant exposure (Calvaresi 2016).

Monitoring Parameters

Apnea of prematurity: Heart rate, number and severity of apnea spells, serum caffeine concentration (as appropriate).

Stimulant: Insomnia, tachycardia.

Reference Range

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)

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

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).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Pregnancy and cirrhosis: Half-life is increased.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Peyona;
  • (AR) Argentina: Cafeina citrato richet | Enerjet;
  • (AT) Austria: Coffekapton | Gencebok | Lecikur | Peyona;
  • (AU) Australia: Amcal alert caffeine | Cafnea | Pharmacy choice stay alert;
  • (BE) Belgium: Gencebok | Peyona;
  • (BG) Bulgaria: Nymusa | Peyona;
  • (BR) Brazil: Fatigan Plus | Peyona;
  • (CH) Switzerland: Peyona;
  • (CL) Chile: Ativase;
  • (CO) Colombia: Caf clin | Cafeinnova | Citrato de cafeina | Peyona | Ticaff;
  • (CZ) Czech Republic: Nymusa | Peyona;
  • (DE) Germany: Coffein | Nymusa | Peyona;
  • (DK) Denmark: Nymusa;
  • (DO) Dominican Republic: Acrocaf;
  • (EC) Ecuador: Citrato de cafeina | Despertol | Ticaff;
  • (EE) Estonia: Cofi-tabs | Gencebok | Kofeiini | Lecikur | Nymusa | Peyona;
  • (EG) Egypt: Caffeinospire;
  • (ES) Spain: Gencebok | Nymusa | Peyona;
  • (FI) Finland: Coffein pharmia | Cofi-tabs | Gencebok | Nymusa | Peyona;
  • (FR) France: Gencebok | Nymusa;
  • (GB) United Kingdom: Fenapin | Gencebok | Nymusa | Peyona | Pro plus;
  • (GR) Greece: Nymusa | Peyona;
  • (HR) Croatia: Peyona;
  • (HU) Hungary: Coffeini | Nymusa | Peyona;
  • (IE) Ireland: Peyona | Pro plus;
  • (IN) India: Apnicaf | Caff aop | Cafirate | Cafneon | Capnea | Noapnea;
  • (IT) Italy: Caffeina citrato monico | Nymusa | Peyona;
  • (JP) Japan: Kafe Soft | Respia;
  • (KW) Kuwait: Peyona;
  • (LT) Lithuania: Nymusa | Peyona;
  • (LV) Latvia: Nymusa | Peyona;
  • (MT) Malta: Nymusa;
  • (MX) Mexico: Peyona | Ticaff | Zaat;
  • (MY) Malaysia: Cafnea | Peyona;
  • (NL) Netherlands: Gencebok | Nymusa | Peyona;
  • (NO) Norway: Koffein | Peyona;
  • (NZ) New Zealand: Caffeine | No doz | No doz plus;
  • (PE) Peru: Citrato de cafeina | D spierto | Taxigen | Vcafa;
  • (PK) Pakistan: Peyona;
  • (PL) Poland: Cafcit | Nymusa | Peyona;
  • (PR) Puerto Rico: Cafcit | Lucidex | No doz;
  • (PT) Portugal: Nymusa | Peyona;
  • (QA) Qatar: Cooper Caffeine Citrate | Peyona;
  • (RO) Romania: Nymusa;
  • (RU) Russian Federation: Coffeine sodium benzoate | Sodium caffeine benzoate;
  • (SA) Saudi Arabia: Peyona;
  • (SE) Sweden: Gencebok | Koffein recip | Nymusa | Peyona;
  • (SI) Slovenia: Nymusa | Peyona;
  • (SK) Slovakia: Nymusa | Peyona;
  • (TN) Tunisia: Cafeine;
  • (TR) Turkey: Kafesit | Kafsiton | Peyona;
  • (TW) Taiwan: Cafnea | Peyona;
  • (UA) Ukraine: Peyona;
  • (UY) Uruguay: Cafnea;
  • (ZW) Zimbabwe: Peppalets
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