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Acetaminophen (paracetamol) and caffeine: Drug information

Acetaminophen (paracetamol) and caffeine: Drug information
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For additional information see "Acetaminophen (paracetamol) and caffeine: Patient drug information" and "Acetaminophen (paracetamol) and caffeine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Excedrin Tension Headache [OTC];
  • Panadol Extra [OTC]
Pharmacologic Category
  • Analgesic, Nonopioid
Dosing: Adult
Pain

Pain: Oral: Acetaminophen 500 mg/caffeine 65 mg/tablet: Two tablets every 6 hours as needed; maximum: 8 tablets (acetaminophen 4,000 mg/caffeine 520 mg) per 24 hours.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Also see individual agents.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use caution. Also see individual agents.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Acetaminophen (paracetamol) and caffeine: Pediatric drug information")

Note: All sources of acetaminophen (eg, prescription, OTC, combination products) should be considered when evaluating a patient's maximum daily dose. To lower the risk for hepatotoxicity, limit daily acetaminophen dose to ≤75 mg/kg/day (maximum number of daily doses determined by product), not to exceed 4,000 mg/day; while recommended doses are generally considered safe, hepatotoxicity has been reported (rarely) even with doses below recommendations (Ref).

Pain; mild muscle aches or headache

Pain; mild muscle aches or headache: Children ≥12 years and Adolescents: Acetaminophen 500 mg/caffeine 65 mg per tablet: 2 tablets every 6 hours as needed; maximum daily dose: 8 tablets per 24 hours (acetaminophen 4,000 mg/caffeine 520 mg per 24 hours); refer to product labeling for additional information.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Mild to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling for acetaminophen or caffeine. Based on adult acetaminophen pharmacokinetic studies, dosage adjustment may not be necessary for short courses. In adult pharmacokinetic studies, plasma concentrations of acetaminophen did not differ in renal impairment patients when compared to healthy patients for short courses of treatment (ie, 3 days); however, accumulation of the glucuronide and sulfate conjugate metabolites in renal impairment has been described following a single dose of acetaminophen up to repeat dosing for 10 days; the clinical significance of this finding is unknown (Ref).

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use caution. Also see individual agents.

Adverse Reactions

See individual agents.

Contraindications

OTC labeling: When used for self-medication, do not use with other drugs containing acetaminophen or if you are allergic to acetaminophen, caffeine, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Hepatotoxicity: Acetaminophen has been associated with severe liver damage. Hepatotoxicity is usually associated with excessive intake and often involves more than one product that contains acetaminophen. Do not exceed more than 6 tablets in 24 hours and do not combine with other products that contain acetaminophen.

• Skin reactions: Serious and potentially fatal skin reactions, including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have occurred rarely with acetaminophen use. Discontinue therapy at the first appearance of skin rash (FDA 2013).

Disease-related concerns:

• Ethanol use: Use with caution with concomitant alcohol use; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

Other warnings/precautions:

• Caffeine: Contains an amount of caffeine similar to one cup of coffee; limit the use of caffeine-containing beverages or foods during therapy.

• Dosage limit: Limit acetaminophen dose from all sources (prescription, OTC, combination products) and all routes of administration (IV, oral, rectal) to <4 g/day (adults and pediatric patients ≥12 years of age).

• Self-medication (OTC use): When used for self-medication, patients should be instructed to contact health care provider if symptoms get worse or new symptoms appear, redness or swelling is present in the painful area, fever lasts >3 days, or pain lasts longer than 10 days.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Excedrin Tension Headache: Acetaminophen 500 mg and caffeine 65 mg [contains benzoic acid, fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow)]

Excedrin Tension Headache: Acetaminophen 500 mg and caffeine 65 mg [aspirin free; contains benzoic acid, fd&c blue #1 (brill blue) aluminum lake, fd&c red #40 (allura red ac dye)]

Excedrin Tension Headache: Acetaminophen 500 mg and caffeine 65 mg [aspirin free; contains benzoic acid, fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]

Panadol Extra: Acetaminophen 500 mg and caffeine 65 mg [contains benzoic acid, fd&c blue #2 (indigo carm) aluminum lake, fd&c yellow #6(sunset yellow)alumin lake]

Generic Equivalent Available: US

No

Pricing: US

Tablets (Excedrin Tension Headache Oral)

500-65 mg (per each): $0.20

Tablets (Panadol Extra Oral)

500-65 mg (per each): $0.20

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.

Administration: Pediatric

Oral: May be administered without regard to meals; consider administration with food if GI upset occurs (based on individual components).

Use: Labeled Indications

Pain: Temporary relief of minor aches and pains caused by headache or muscle aches.

Medication Safety Issues
International issues:

Anacin New [India] may be confused with Anacin brand name for lidocaine/prilocaine [Korea]; Anacin 81 brand name for aspirin [Puerto Rico]; Anacin 3 brand name for acetaminophen [Taiwan]

Other safety concerns:

Duplicate therapy issues: This product contains acetaminophen, which may be a component of other combination products. Do not exceed the maximum recommended daily dose of acetaminophen.

Metabolism/Transport Effects

Refer to individual components.

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

Alcohol (Ethyl): May increase hepatotoxic effects of Acetaminophen. Risk C: Monitor

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

Atazanavir: May increase serum concentration of UGT1A1 Substrates. Management: Do not use UGT1A1 substrates for which small increases in exposure can cause serious adverse effects together with atazanavir, and use caution with any UGT1A1 substrate, even when small changes in exposure are less likely to cause serious adverse effects. Risk D: Consider Therapy Modification

Atomoxetine: May increase hypertensive effects of Sympathomimetics. Atomoxetine may increase tachycardic effects of Sympathomimetics. Risk C: Monitor

Belumosudil: May increase serum concentration of UGT1A1 Substrates. Management: Avoid coadministration of belumosudil with substrates of UGT1A1 for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the UGT1A1 substrate may be required. Risk D: Consider Therapy Modification

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

Busulfan: Acetaminophen may increase serum concentration of Busulfan. 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

CarBAMazepine: May increase metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. 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

Dapsone (Topical): May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Risk C: Monitor

Dasatinib: Acetaminophen may increase hepatotoxic effects of Dasatinib. Dasatinib may increase serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and dasatinib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider Therapy Modification

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

Flucloxacillin: May increase adverse/toxic effects of Acetaminophen. Specifically, the risk for high anion gap metabolic acidosis may be increased. Risk C: Monitor

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

Fosphenytoin-Phenytoin: May decrease serum concentration of Acetaminophen. Specifically, serum concentrations of acetaminophen may be decreased (leading to decreased efficacy), but the formation of the toxic N-acetyl-p-benzoquinone imine (NAPQI) metabolite may be increased (leading to increased hepatotoxicity). 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

Imatinib: Acetaminophen may increase hepatotoxic effects of Imatinib. Risk C: Monitor

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Acetaminophen may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). 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

Isoniazid: May increase hepatotoxic effects of Acetaminophen. Isoniazid may increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor

Kratom: May increase adverse/toxic effects of Sympathomimetics. Risk X: Avoid

LamoTRIgine: Acetaminophen may decrease serum concentration of LamoTRIgine. Risk C: Monitor

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

Local Anesthetics: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor

Lorlatinib: May decrease serum concentration of Acetaminophen. 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

MetyraPONE: May increase serum concentration of Acetaminophen. More importantly, by inhibiting the conjugative metabolism of acetaminophen, metyrapone may shift the metabolism towards the oxidative route that produces a hepatotoxic metabolite. Risk X: Avoid

MigALAstat: Caffeine and Caffeine Containing Products may decrease serum concentration of MigALAstat. Risk X: Avoid

Mitapivat: May decrease serum concentration of UGT1A1 Substrates. Risk C: Monitor

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

Nitric Oxide: May increase adverse/toxic effects of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. 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

PHENobarbital: May increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor

Phenylephrine (Systemic): Acetaminophen may increase serum concentration of Phenylephrine (Systemic). 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

Prilocaine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor for signs of methemoglobinemia when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid use of these agents with prilocaine/lidocaine cream in infants less than 12 months of age. Risk C: Monitor

Primaquine: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Primaquine. Specifically, the risk for methemoglobinemia may be increased. Management: Avoid concomitant use of primaquine and other drugs that are associated with methemoglobinemia when possible. If combined, monitor methemoglobin levels closely. Risk D: Consider Therapy Modification

Primidone: May increase metabolism of Acetaminophen. Specifically, formation of the hepatotoxic NAPQI metabolite may be increased. Risk C: Monitor

Probenecid: May increase serum concentration of Acetaminophen. Probenecid may also limit the formation of at least one major non-toxic metabolite, possibly increasing the potential for formation of the toxic NAPQI metabolite. Management: Consider limiting acetaminophen use in combination with probenecid. Probenecid may reduce clearance of acetaminophen to one of its non-toxic metabolities, increasing the risk for acetaminophen toxicity, even a lower doses. Risk D: Consider Therapy Modification

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

RifAMPin: May increase hepatotoxic effects of Acetaminophen. RifAMPin may decrease serum concentration of Acetaminophen. Risk C: Monitor

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 Nitrite: Methemoglobinemia Associated Agents may increase adverse/toxic effects of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. 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

SORAfenib: Acetaminophen may increase hepatotoxic effects of SORAfenib. SORAfenib may increase serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and sorafenib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider Therapy Modification

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

Vaccines: Acetaminophen may decrease therapeutic effects of Vaccines. Management: Consider avoiding routine prophylactic use of acetaminophen before or during vaccine administration when possible. Acetaminophen is still recommended to treat fevers and/or pain that occurs after vaccination. Risk D: Consider Therapy Modification

Vitamin K Antagonists: Acetaminophen may increase anticoagulant effects of Vitamin K Antagonists. This appears most likely with daily acetaminophen doses exceeding 1.3 or 2 g/day for multiple consecutive days. 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

Treatment for migraine headaches in pregnant patients should be individualized (AHS [Ailani 2021]). The acute treatment of migraine headaches in pregnant patients should be initiated with acetaminophen. When acetaminophen monotherapy is ineffective, acetaminophen in combination with caffeine may be considered. Do not exceed the total recommended daily dose of acetaminophen or caffeine; caffeine intake from all sources should be limited to ≤200 mg/day during pregnancy (ACOG 2022).

Also refer to individual monographs for additional information.

Breastfeeding Considerations

Acetaminophen and caffeine are present in breast milk.

Treatment for migraine headaches in lactating patients should be individualized (AHS [Ailani 2021]). The acute treatment of migraine headaches in lactating patients should be initiated with acetaminophen. When acetaminophen monotherapy is ineffective, acetaminophen in combination with caffeine may be considered. Do not exceed the total recommended daily dose of acetaminophen or caffeine (ACOG 2022).

Also refer to individual monographs for additional information.

Dietary Considerations

Limit the use of caffeine-containing beverages or foods.

Mechanism of Action

Acetaminophen: Although not fully elucidated, the analgesic effects are believed to be due to activation of descending serotonergic inhibitory pathways in the CNS. Interactions with other nociceptive systems may be involved as well (Smith 2009). Antipyresis is produced from inhibition of the hypothalamic heat-regulating center.

Caffeine: Blocks adenosine receptors (mainly A1 and A2A subtypes), induces calcium mobilization from the sarcoplasmic reticulum and inhibits calcium reuptake, increases levels of cyclic AMP by inhibiting phosphodiesterase (Cappelletti 2015).

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

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

  • (AE) United Arab Emirates: Cafenol | Excedrin tension headache | Midrone | Omol | Panadol extra | Panadol extra optizorb | Panadrex max;
  • (AR) Argentina: Dolanet | Mejoral cafeina | Parageniol caff;
  • (AT) Austria: Vivimed;
  • (AU) Australia: Amcal + para extra | Amcal+para extra | Apohealth paracetamol plus caffeine | Blooms the chemist paracetamol plus caffeine | Chemists' own paracetamol extra | Chemmart pharmacy paracetamol extra | Coles pain relief extra | Gold cross paracetamol plus caffeine | Hedanol extra | Help@hand for pain relief extra | Medichoice paracetamol extra | Medihealth paracetamol & caffeine | Medix pain relief extra | Medreich paracetamol extra | Nyal paracetamol plus caffeine | Panadol extra | Panadol extra optizorb | Paracetamol/caffeine gxp | Pharmacist formula paracetamol xtra | Pharmacy action paracetamol extra | Pharmacy choice paracetamol extra | Pharmacy health paracetamol & caffeine | Pharmacy health paracetamol extra | Priceline paracetamol & caffeine | Priceline paracetamol extra | Priceline pharmacy paracetamol & caffeine | Terrywhite chemmart paracetamol extra | Trust umol extra | Vidalife para xtra;
  • (BD) Bangladesh: Ace plus | Ampol plus | Asmol plus | Atp extra | Benalgin plus | Cafenol | Caffo | Caftyl | Capdol | Clofamol | Dc plus | Fap plus | Fea plus | Momodol extra | Napa extra | Neopara plus | Nor plus | Pac | Pamix extra | Paracet plus | Paragesic c | Paraxia Plus | Pax | Pol plus | Pyrenol | Pyrex plus | Pyrexil plus | Qcet cafe | Reliv plus | Sb opa plus | Tacs | Tamen turbo | Temfin | Temol extra | Temrif plus | Ty Plus | Ucet extra;
  • (BE) Belgium: Antigriphine | Dafalgan plus caffeine | Finidol | Finimal;
  • (BF) Burkina Faso: Anapain extra | Panadol extra | Strimol extra;
  • (BG) Bulgaria: Apap extra | Panadol extra | Tylol Plus;
  • (BR) Brazil: Abidor caf | Cefadrin | Maxidrin | Paracetamol+cafeina | Tylenol DC;
  • (CH) Switzerland: Dafalgan extra | Dialgine | Dolo kranit | Panadol extra | Sanalgin N;
  • (CI) Côte d'Ivoire: Algesic extra | Analgan extra | Efdol Caffeine | Panda extra | Para caf | Strimol extra;
  • (CL) Chile: Kitadol max | Panadol plus | Panagesic con cafeina | Saridon;
  • (CN) China: Bufferin plus | Jia he bai fu ning | Paracetamol and caffeine;
  • (CO) Colombia: Acetaminofen con cafeina | Acetaminofen+cafeina | Acetaminofen+cafeina forte | Adorem plus | Analper caf | Antalgine | Antalgine forte | Atacadol activo | Balance forte | Balanceforte | Dolex forte | Dolofen forte;
  • (CZ) Czech Republic: Panadol extra | Panadol extranovum | Paracetamol/kofein Dr. Muller pharma | Paracetamol/kofein xantis | Paralen esxtra | Paramax Combi | Parapyrex combi;
  • (DE) Germany: Azur | Coffalon n | Fineural paracetamol coffein | Octadon p | Optalidon | Optalidon mit Paracetamol & Coffein | Para caf | Paracetamol plus coffein axicur | Temagin paracetamol plus | Vivimed mit Coffein gegen Kopfschmerzen | Zentragress;
  • (DO) Dominican Republic: Acrogesico forte | Boska | Pain Max ultra | Sinedol ultra | Ultrafen ultra | Winasorb ultra;
  • (EC) Ecuador: Bephen forte | Dolgitan forte | Dominal | Finalin | Finalin forte | Finalin junior plus | Kronafen | Migra doloxen | Normotemp migra | Paracetamol cafeina indeurce | Rapid migra | Rapiflash | Sinalgia forte | Tapsin analgesico | Tempra plus;
  • (EE) Estonia: Panadol extra | Paramax extra;
  • (EG) Egypt: Abimol | Bienadol | Gescamoli extra | Jencafemol | Panadol extra | Prontoplus | Pyral extra | Vetocetamol;
  • (ES) Spain: Gelocatil plus;
  • (ET) Ethiopia: Acetaminophen and caffeine | Paingo extra | Panadol extra | Paracetamol + caffeine | Paracetamol and caffeine | Snip pain;
  • (FI) Finland: Panadol coffein | Panadol comp | Paramax Comp;
  • (FR) France: Algodol cafeine | Cefaline hauth | Cetafeine | Claradol cafeine | Dalfeine | Dolidon | Prontadol;
  • (GB) United Kingdom: Hedex extra | Mandanol Plus | Nurodol | Panadol extra | Paracetamol & caffeine | Paracetamol Extra Strength Pain Relief | Paracetamol plus | Solpadeine Headache;
  • (GR) Greece: Algine | Apotel Extra | Panadol extra;
  • (HK) Hong Kong: Analgesic | Arfen plus | Christamol extra | Fortolin Extra | Ho chai kung analgesic | Onilene | Panadol extra | Panadol extra advance | Panadol menstrual | Paragesic | Paramol Extra | Paramol forte | Picapan | Pocetmol | Pontamol | Qualafin | Sanladol | Suta Extra | Xenidel;
  • (HR) Croatia: Panadol extra;
  • (HU) Hungary: Miralgin | Panadol extra | Panadol rapid extra | Paramax Comp;
  • (ID) Indonesia: Bodrex | Boska | Cafmosol | Exadon | Head-o | Indo sakit kepala | Oskadon | Panadol extra | Paramex sk | Poldan | Prodol | Rataka;
  • (IE) Ireland: Panadol cold & flu relief | Panadol extra | Paralief extra;
  • (IL) Israel: Paramol Plus;
  • (IN) India: Aaram | Algina plus | Anacin new | Cafepar | Cafipar | Combiflam plus | Crocin pain relief | Doliza Plus | Dolopar | Noache | Pacimol active | Palgin-n | Pantac | Paraldim | Saridon advance | Saridon plus | Senmol active | Stopache | Sudrek | Trimol-s | X cold;
  • (IQ) Iraq: Acetamol extra | Paracedol extra | Piodol extra | Samadol extra;
  • (JO) Jordan: Adol extra | Antamol | Feverol Extra | Midrone | Pamol extra | Panadol extra | Panda extra;
  • (KE) Kenya: Cinepar extra | Curamol plus | Napa extra | Neladol extra | Painotab | Panadol extra | Panadol extra with optizorb | Sonadol extra | Sonamol extra | Uncle joe extra;
  • (KR) Korea, Republic of: Acephen | Aceteming | Anacxen | Anophen | Dgmif aceca | Ecathina | Penzal s | Saridon s | Tanaxen;
  • (KW) Kuwait: Adol extra | Panadol extra | Panadrex max;
  • (LB) Lebanon: Adol extra | Dolocet extra | Excedrin aspirin free | Panadol extra | Panadol extra with optizorb;
  • (LT) Lithuania: Panadol extra | Panadol extra optizorb | Paramax extra;
  • (LU) Luxembourg: Algostase | Antigriphine | Finimal;
  • (LV) Latvia: Panadol extra | Paramax extra;
  • (MA) Morocco: Algik | Claradol cafeine | Panalgic;
  • (MX) Mexico: Andox Plus | Andox t | Bio nrgy | Mejoral 5.0 | Panadol plus | Quimofeina | Saridon | Sedalmerck max | Sindo | Tempire pfc | Tempra boost | Tempra es3;
  • (MY) Malaysia: Napa extra | Panadol extra;
  • (NG) Nigeria: Albemol plus | Bacarex | Barogin | Bioramol extra | Bleorex | Consuka | Decoco | Emcap extra | Emydrex | Forpain | Henacaff | Jubidrex | Koheal | Medik 55 | Olidrex | Panadol extra | Panextra | Paraunic extra | Poledrex | Sakura extra | Sandrex | Specdrex | Stalpara extra | Surelgin | Suremol extra | Talidrex | Uncle leo paracetamol & caffeine | Zakurex | Zapar extra;
  • (NL) Netherlands: Albert Heijn Paracetamol/coffeine | Idyl paracetamol/coffeine | Livsane paracetamol met coffeine | Panadol plus | Para-don | Paracetamol comp | Paracetamol comp. | Paracetamol/coffeine | Paracetamol/coffeine triangle Pharma | Roter paracof | San paracetamol+coffeine;
  • (NO) Norway: Paracetduo;
  • (NZ) New Zealand: Panadol extra | Paracetamol & caffeine;
  • (PE) Peru: Tapsin analgesico | Tapsin forte;
  • (PH) Philippines: Calpol extra | Reliepain | Rexidol forte;
  • (PK) Pakistan: Adol extra | Amadol | Amole plus | Calpol plus | Cepmol extra | Danidol extra | Delmol extra | Detamol | Estadol | Febrol xtra | Fevamol extra | Feveren extra | Mytomol extra | Panadol extra | Panafin | Para plus | Paradeine plus | Paragray extra | Parapol extra | Parol plus | Pedrol | Rgesic | Samophen extra | Terinal | Trigin | Tyladol | Tylol | Weladol plus | Zancpal extra;
  • (PL) Poland: Etoran extra | Gripex control duo | Kofepar | Pabialgin neo | Panacit extra | Paramax Comp;
  • (PR) Puerto Rico: Excedrin tension headache | Panadol extra;
  • (PT) Portugal: Ben u ron caff | Nygen | Panadol extra | Paramolan caf;
  • (PY) Paraguay: Fiedol | Opadol;
  • (QA) Qatar: Adol Extra | Dolocet Extra | Excedrin Tension Headache | Fevadol Extra | Feverol Extra | Midrone Extra | Omol Extra | Panadol Cold and Flu Early Symptoms | Panadol Extra | Panadol Extra Optizorb | Panadrex Max | Panalex Extra | Panda Extra;
  • (RO) Romania: Antigripal pc | Efisen c | Extradol | Panacit extra | Panadol extra | Paracof;
  • (RU) Russian Federation: Migrenium | Migrenol | Panadol extra | Paralen extra | Solpadeine fast | Strike plus | Strimol plus;
  • (SA) Saudi Arabia: Adol extra | Amol extra | Fevadol extra | Midrone | Panadol extra | Panda extra | Prontopyrin plus;
  • (SE) Sweden: Alvedon comp | Paracut comp;
  • (SG) Singapore: Panadol extra;
  • (SI) Slovenia: Panadol extra | Paramax Comp;
  • (SK) Slovakia: Panadol extra | Paracetamol/kofein Dr. Muller pharma | Paracetamol/kofein xantis | Paralen extra | Paramax extra | Parapyrex combi;
  • (SL) Sierra Leone: Samdrex;
  • (SR) Suriname: Ace plus | Da paracetamol met coffeine | Finimal | Idyl paracetamol/coffeine | Leidapharm paracetamol/coffeine | Livsane paracetamol met coffeine | Paracetamol + caffeine | Paracetamol plus coffeine | Paracetamol/coffeine | Paracetamol/coffeine sanias | Paracetamol/coffeine teva;
  • (TN) Tunisia: Adol extra | Algesic extra | Algidol extra | Analgan extra | Novadol extra | Panadol extra;
  • (TR) Turkey: Adafen | Comax | Darvolin | Geralgine p | Gripal | Kataljin p | Medafein | Nopain plus | Novaldon | Pacofen s | Panadol extra | Paramidon | Setakaf | Tylol Plus | Vermol;
  • (TW) Taiwan: Ac | Aceca | Acecaine | Analgesic | Analgesic extra tablets taisho | Anliton | Arfen plus | Bae shu teng extra | Bytonlin | Carmeiton | Chinteng Tozy Extra | Cold free aceca | Cosuston extra | Daraffin | Depyretin extra | Fotonrin | Paceton | Panadol extra | Panadol extra optizorb | Panatol | Penidol | Pinsu extra | Proton Forte | Puanton | Pulodol | Punaolin | Putonrin | Pyrinin | Pyrudon Extra | Suta Extra | Take | Tempte | Tinten extra | Toncachi | Tonsiau | Tozy | U Chiu Analgesic | U chu plus analgesic | Welger Extra Strength Pain Relief;
  • (UA) Ukraine: Bol ran neo | Cafapar | Citramon | Copacil | Pafein | Panadol extra | Panadol extra advance | Rapimax;
  • (UG) Uganda: Adol extra | Curamol plus | Extradol | Finadol ultra | Fremol extra | Kamadol plus | Painol p | Painotab | Panadol extra | Panadol extra with optizorb | Polymol extra | Snip pain | Strimol extra;
  • (UY) Uruguay: Dolex cafeina | Dolosedol Cafeina;
  • (VE) Venezuela, Bolivarian Republic of: Acetaminofen cafeina | Atamel plus | Cafenol | Parsel plus | Tempra plus;
  • (VN) Viet Nam: Acetab extra | Bivinadol extra | Datadol extra | Glotadol extra | Hapacol extra | Ophazidon | Pancidol extra plus;
  • (ZM) Zambia: Curamol plus | Painol p;
  • (ZW) Zimbabwe: Asalen
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