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Ibuprofen and acetaminophen: Drug information

Ibuprofen and acetaminophen: Drug information
(For additional information see "Ibuprofen and acetaminophen: Pediatric drug information" and see "Ibuprofen and acetaminophen: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Acetaminophen-Ibuprofen [OTC];
  • Advil Dual Action [OTC];
  • Motrin Dual Action [OTC]
Pharmacologic Category
  • Analgesic, Nonopioid;
  • Nonsteroidal Anti-inflammatory Drug (NSAID), Oral
Dosing: Adult
Analgesic

Analgesic: Oral: Acetaminophen 250 mg/ibuprofen 125 mg per tablet: Two tablets every 8 hours as needed (maximum: 6 tablets [acetaminophen 1.5 g/ibuprofen 750 mg]/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; use with caution. Also refer to individual agents.

KDIGO 2012 guidelines provide the following recommendations for nonsteroidal anti-inflammatory drugs:

eGFR 30 to <60 mL/minute/1.73 m2: Avoid use in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m2: Avoid use.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution to avoid adverse effects and discontinue if hepatic function worsens. Also see individual agents.

Dosing: Older Adult

Refer to adult dosing. Unless alternative agents are ineffective and a gastroprotective agent can be administered, avoid short-term scheduled use in combination with corticosteroids, anticoagulants, or antiplatelet agents or chronic use with or without medications that increase risk for bleeding (Ref).

Dosing: Pediatric

(For additional information see "Ibuprofen and acetaminophen: Pediatric drug information")

Analgesic

Analgesic: Children ≥12 years and Adolescents: Acetaminophen 250 mg/ibuprofen 125 mg per tablet: Oral: Two tablets every 8 hours as needed; maximum daily dose: 6 tablets/24 hours.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, clearance may be reduced; active metabolites may accumulate. Use with caution; initiate at lower doses or longer dosing intervals followed by careful titration. See individual monographs for specific adjustments.

KDIGO 2012 guidelines provide the following recommendations for nonsteroidal anti-inflammatory drugs (Ref):

eGFR 30 to <60 mL/minute/1.73 m2: Avoid use in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m2: Avoid use.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, product contains acetaminophen; use with caution. Cases of hepatotoxicity at daily acetaminophen dosages <4,000 mg/day have been reported. See individual monographs.

Adverse Reactions

See individual agents.

Contraindications

OTC labeling: When used for self-medication, do not use if previous allergic reaction to any other pain reliever/fever reducer; do not use with other drug products containing acetaminophen; prior to or following cardiac surgery.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure to ibuprofen, anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Use of ibuprofen is contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including fatal myocardial infarction (MI) and stroke. Risk may occur early during treatment and may increase with dose and duration of use. Avoid use in patients with a recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk (ACC/AHA [Amsterdam 2014]). Avoid use in patients undergoing revascularization procedures. New-onset hypertension or exacerbation of hypertension may occur. NSAIDs may also impair response to antihypertensive agents; monitor BP; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure (FDA 2015).

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects that may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events: NSAIDs cause an increased risk of serious GI inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. Use with caution in patients on concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids), advanced hepatic disease, coagulopathy, use of alcohol, or in elderly patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events. In patients with a history of GI ulcer bleeding requiring NSAID therapy, a COX-2 inhibitor in combination with a proton pump inhibitor is recommended to reduce the risk of recurrent bleeding (Barkun 2019). Discontinue use if GI bleeding occurs. Use is contraindicated in patients with active GI bleeding or peptic ulcer. Some product labeling contraindicates use in patients with a history of gastrointestinal bleeding or perforation related to NSAID therapy and/or patients with a history of ulcerative colitis, Crohn disease, recurrent peptic ulceration, or GI hemorrhage.

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Rarely, NSAID use has been associated with potentially severe blood dyscrasias.

• Hepatotoxicity: Acetaminophen has been associated with acute liver failure, at times resulting in liver transplant and death. Hepatotoxicity is usually associated with excessive acetaminophen intake and often involves >1 product that contains acetaminophen. Do not exceed the maximum recommended daily dose (>4 g daily in adults) (Lancaster 2015). Hepatotoxicity has been reported with therapeutic doses of acetaminophen in patients with alcohol use disorder. In addition, chronic daily dosing may also result in liver damage in some patients (Bolesta 2002). Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, liver necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, angiotensin-converting enzyme [ACE]-inhibitors). Monitor potassium closely.

• Infection: May mask signs and symptoms of infection (eg, pain, fever, inflammation) resulting in delayed diagnosis.

• Ophthalmic events: Ophthalmologic adverse effects have been reported with NSAID use. Discontinue therapy and refer for ophthalmologic evaluation if symptoms occur.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors or angiotensin II receptor blockers, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: May cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; may occur without warning. Discontinue use at first sign of skin rash (or any other hypersensitivity).

Disease-related concerns:

• Aseptic meningitis: NSAIDs may increase the risk of aseptic meningitis, especially in patients with systemic lupus erythematosus and mixed connective tissue disorders.

• Asthma: Use with caution in patients with asthma. Use of ibuprofen is contraindicated in patients with aspirin-sensitive asthma; severe and potentially fatal bronchospasm may occur.

• Coronary artery bypass graft surgery: Avoid ibuprofen use in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.

• Coronavirus disease 2019 (COVID-19): Clinical or population-based data regarding the risks of NSAIDs in the setting of COVID-19 are limited (FDA Safety Communication 2020; Kim 2020). Some experts recommend the use of acetaminophen as the preferred antipyretic agent, when possible, and if NSAIDs are needed, to use the lowest effective dose and shortest duration (EMA 2020; Kim 2020). In general, for patients already taking an NSAID for a comorbid condition, it is recommended to continue the NSAID as directed by their health care provider (EMA 2020; NIH 2020; WHO 2020).

• Ethanol use: Use acetaminophen with caution in patients with alcoholic liver disease; consuming ≥3 alcoholic drinks/day may increase the risk of liver damage. Patients should avoid ethanol or limit to <3 drinks/day.

• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced doses may be required due to extensive hepatic metabolism. Patients with advanced hepatic disease are at an increased risk of GI bleeding and kidney failure with NSAIDs (AASLD [Biggins 2021]; AASLD [Runyon 2013]).

Special populations:

• Older adult: Older adult patients are at increased risk for adverse effects (especially peptic ulceration, CNS effects, renal toxicity) from NSAIDs even at low doses; use with caution.

Other warnings/precautions:

• Self-medication (OTC use): Should not be used with other products containing acetaminophen. Patients should be instructed to contact health care provider if new symptoms occur, if redness or swelling occurs in the painful area, or for pain lasting >10 days. Consuming ≥3 alcoholic beverages/day or taking longer than recommended may increase the risk of GI bleeding. Also see individual agents.

Warnings: Additional Pediatric Considerations

Hepatoxicity has been reported in patients using acetaminophen. In pediatric patients, this is most commonly associated with supratherapeutic dosing, more frequent administration than recommended, and use of multiple acetaminophen-containing products; however, hepatotoxicity has been rarely reported with recommended dosages (AAP [Sullivan 2011]; Heard 2014). All sources of acetaminophen (eg, prescription, OTC, combination) should be considered when evaluating a patient's maximum daily dose. To lower the risk for hepatotoxicity, the maximum daily acetaminophen dose should be limited to ≤75 mg/kg/day (maximum of 5 daily doses), not to exceed 4,000 mg/day (AAP [Sullivan 2011]; Heard 2014; Krenzelok 2012; Lavonas 2010). Acetaminophen avoidance or a lower total daily dose (2,000 to 3,000 mg/day) has been suggested for adults with increased risk for acetaminophen hepatotoxicity (eg, malnutrition, certain liver diseases, use of drugs that interact with acetaminophen metabolism); similar data are unavailable in pediatric patients (Hayward 2016; Larson 2007; Worriax 2007).

A single-center, 10-year, retrospective review of pediatric patients diagnosed with acute kidney injury (AKI) (n=1,015; ages ≤18 years) reported nonsteroidal anti-inflammatory drugs (NSAIDs) as a potential cause of AKI in 2.7% of patients (n=27); a higher incidence (6.6%) was reported when additional exclusion factors were included in the data analysis. Dosing information was available for 74% of the NSAID-associated AKI cases (n=20); dosing was within the recommended range in 75% (n=15) of these cases. The median age of children with NSAID-associated AKI was 14.7 years (range: 0.5 to 17.7 years) and 15% of patients were <5 years and more likely to require dialysis than the older patients. Some experts suggest the incidence of NSAID-associated AKI found in this study is conservative due to aggressive exclusion criteria (eg, concurrent aminoglycoside or other nephrotoxic therapy) and the actual incidence may be higher (Brophy 2013; Misurac 2013).

Product Availability

Combogesic (acetaminophen 325 mg and ibuprofen 97.5 mg) tablets: FDA approved March 2023; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Combogesic is indicated in adults for the short-term management of mild to moderate acute pain. Consult the prescribing information for additional information.

Combogesic IV (acetaminophen 1,000 mg/100 mL and ibuprofen 300 mg/100 mL) Single Dose Vials: FDA approved October 2023; anticipated availability early 2024. Information pertaining to this product within the monograph is pending revision. Combogesic IV is indicated in adults where an IV route of administration is clinically necessary for relief of mild to moderate pain or in the management of moderate to severe pain as an adjunct to opioid analgesics.

Dosage Forms: US

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

Tablet, Oral:

Acetaminophen-Ibuprofen: Acetaminophen 250 mg and ibuprofen 125 mg

Advil Dual Action: Acetaminophen 250 mg and ibuprofen 125 mg

Motrin Dual Action: Acetaminophen 250 mg and ibuprofen 125 mg [contains corn starch]

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Advil Dual Action Oral)

125-250 mg (per each): $0.20

Tablets (Motrin Dual Action Oral)

125-250 mg (per each): $0.17

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: Adult

Oral: May be administered with food or milk if stomach upset occurs.

Administration: Pediatric

Oral: Administer without regard to meals. May be administered with food or milk if GI upset occurs.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at the following website, must be dispensed with this medication:

Combogesic: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209471s000lbl.pdf#page=28

Use: Labeled Indications

Pain, minor: Temporary relief of minor aches and pains due to headache, backache, toothache, menstrual cramps, muscular aches, and minor pain of arthritis.

Medication Safety Issues
Older Adult: High-Risk Medication:

Beers Criteria: Ibuprofen is identified in the Beers Criteria as a potentially inappropriate medication to be avoided for chronic use in patients 65 years and older (unless alternative agents are ineffective and patient can receive concomitant gastroprotective agent) due to increased risk of GI bleeding and peptic ulcer disease in older adults in a high-risk category (eg, older than 75 years of age or receiving concomitant oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents). In addition, avoid for short-term scheduled use in combination with oral/parenteral corticosteroids, anticoagulants, or antiplatelet agents unless alternatives are ineffective and patient can receive concomitant gastroprotective agent (Beers Criteria [AGS 2023]).

International issues:

Maxigesic brand name for ibuprofen/acetaminophen [Australia, New Zealand, Singapore] but also brand name for diclofenac sodium/paracetamol [India].

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy

Abrocitinib: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the hepatotoxic effect of Acetaminophen. Risk C: Monitor therapy

Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Risk C: Monitor therapy

Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Apixaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin and nonsteroidal anti-inflammatory agents (NSAIDs) due to the increased risk of bleeding. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy

Busulfan: Acetaminophen may increase the serum concentration of Busulfan. Risk C: Monitor therapy

Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

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

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Clofarabine: OAT1/3 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider therapy modification

Dabigatran Etexilate: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy

Dasatinib: Acetaminophen may enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the 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

Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy

Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Drospirenone-Containing Products: May enhance the hyperkalemic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Edoxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

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

Fluconazole: May increase the serum concentration of Ibuprofen. Risk C: Monitor therapy

Fosphenytoin-Phenytoin: May decrease the 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 therapy

Heparin: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or nonsteroidal anti-inflammatory agents (NSAIDs) if coadministration is required. Risk D: Consider therapy modification

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy

HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Imatinib: Ibuprofen may decrease the serum concentration of Imatinib. Specifically, ibuprofen may decrease intracellular concentrations of imatinib, leading to decreased clinical response. Management: Consider using an alternative to ibuprofen in patients who are being treated with imatinib. Available evidence suggests other NSAIDs do not interact in a similar manner. Risk D: Consider therapy modification

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Acetaminophen may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

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

Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Ketorolac (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Ketorolac (Systemic). Risk X: Avoid combination

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

Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Management: Consider reducing the lithium dose when initiating a NSAID. Monitor for increased lithium therapeutic/toxic effects if a NSAID is initiated/dose increased, or decreased effects if a NSAID is discontinued/dose decreased. Risk D: Consider therapy modification

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

Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider therapy modification

Lorlatinib: May decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy

Lumacaftor and Ivacaftor: May decrease the serum concentration of Ibuprofen. Risk C: Monitor therapy

Macimorelin: Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

MetFORMIN: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of MetFORMIN. Risk C: Monitor therapy

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Avoid coadministration of higher dose methotrexate (such as that used for the treatment of oncologic conditions) and NSAIDs. Use caution if coadministering lower dose methotrexate and NSAIDs. Risk D: Consider therapy modification

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

MetyraPONE: May increase the 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 combination

Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination

Mipomersen: Acetaminophen may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy

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

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased. Risk X: Avoid combination

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

PEMEtrexed: Ibuprofen may increase the serum concentration of PEMEtrexed. Management: In patients with an estimated creatinine clearance of 45 to 79 mL/min, avoid ibuprofen for 2 days before, the day of, and 2 days following the administration of pemetrexed. Monitor for increased pemetrexed toxicities if combined. Risk D: Consider therapy modification

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

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

Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Phenylephrine (Systemic): Acetaminophen may increase the serum concentration of Phenylephrine (Systemic). Risk C: Monitor therapy

Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium Salts: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Avoid coadministration of pralatrexate with nonsteroidal anti-inflammatory drugs (NSAIDs). If coadministration cannot be avoided, closely monitor for increased pralatrexate serum levels or toxicity. Risk D: Consider therapy modification

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy

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

Probenecid: May increase the 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

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor therapy

Quinolones: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy

RifAMPin: May enhance the hepatotoxic effect of Acetaminophen. RifAMPin may decrease the serum concentration of Acetaminophen. Risk C: Monitor therapy

Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification

Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

SORAfenib: Acetaminophen may enhance the hepatotoxic effect of SORAfenib. SORAfenib may increase the 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

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Tenofovir Products: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose due to a potential risk of acute renal failure. Diclofenac appears to confer the most risk. Risk D: Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Tolperisone: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Tricyclic Antidepressants may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vaccines: Acetaminophen may diminish the therapeutic effect 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

Valproate Products: Ibuprofen may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy

Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider alternatives to this combination when possible. If the combination must be used, monitor coagulation status closely and advise patients to promptly report any evidence of bleeding or bruising. Risk D: Consider therapy modification

Voriconazole: May increase the serum concentration of Ibuprofen. Specifically, concentrations of the S-(+)-ibuprofen enantiomer may be increased. Risk C: Monitor therapy

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Reproductive Considerations

Refer to individual monographs.

Pregnancy Considerations

Acetaminophen crosses the placenta (Naga Rani 1989).

Refer to individual monographs for additional information.

Breastfeeding Considerations

Acetaminophen and ibuprofen are present in breast milk (Notarianni 1987; Rigourd 2014).

Refer to individual monographs for additional information.

Monitoring Parameters

CBC (periodically with long term use), BP (during initiation and periodically thereafter); hepatic function; renal function (in patients at risk for renal impairment), relief of pain.

Mechanism of Action

Acetaminophen: The mechanism of acetaminophen is not fully elucidated; it produces analgesia by increasing the pain threshold.

Ibuprofen: Ibuprofen reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties.

Pharmacokinetics (Adult Data Unless Noted)

Refer to individual agents.

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

  • (AE) United Arab Emirates: Maxigesic;
  • (AR) Argentina: Bengue caps | Causalon gesic | Duomax | Duomax vl | Tafirol flex;
  • (AU) Australia: Advilduo paracetamol+ibuprofen | Amcal Paracetamol & Ibuprofen | Apohealth ibuprofen plus paracetamol | Avallon paracetamol and ibuprofen | Blooms the chemist ibuprofen plus paracetamol | Bpa paracetafen | Bpa paracetamol + ibuprofen | Chemists own ibuprofen + paracetamol duo | Chemists' own ibuprofen + paracetamol duo | Combigesic | Combimol ibuprofen + paracetamol | David craig paracetamol and ibuprofen | Dymafen | Gesicomb | Ibumol double action pain relief | Ibupane | Maxigesic | Maxofen | Medreich paracetamol and ibuprofen | Mersynofen | Nuromol | Nuromol dual action pain relief | Paracetamol & Ibuprofen | Pharmacist formula ibuprofamol | Pharmacy action paracetamol & Ibuprofen | Pharmacy Choice Ibuprofen & Paracetamol | Pharmacy health paracetamol & ibuprofen | Pharmacy health paracetamol and ibuprofen | Pharmacy plus moverex | Priceline pharmacy paracetamol & ibuprofen | Priceline pharmacy paracetamol and ibuprofen | Soul pattinson paracetamol and ibuprofen | Spiro lifecare ibuprofen + paracetamol | Terrywhite chemmart paracetamol + ibuprofen | Terrywhite chemmart paracetamol and ibuprofen | Trust fenmol;
  • (BE) Belgium: Combophen | Nuralgan;
  • (BF) Burkina Faso: Asmoflam | Ibumol | Lexofen plus | Paraflam | Parofen;
  • (BG) Bulgaria: Lekadol complex | Metafen max | Nurulin duo;
  • (BR) Brazil: Algi-danilon | Algi-itamanil | Luftafem | Nuromol | Reuplex;
  • (CH) Switzerland: Paraconica plus;
  • (CI) Côte d'Ivoire: Asmoflam | Brupal forte | Genforte | Ibutamol | Kilmol | Lytamol plus | Parofen | Supafen;
  • (CL) Chile: Adona | Artri tapsin | Dolo octirona | Gedol | Ibupirac compuesto | Kitadol duo | Lumdol | Midol | Predual Di;
  • (CN) China: Bao shi tai | Brustan | Compound ibuprofen;
  • (CZ) Czech Republic: Cetalgen;
  • (DE) Germany: Duoval | Paracetamol/Ibuprofen Acino | Paracetamol/Ibuprofen ratiopharm;
  • (DO) Dominican Republic: Algimax | Doloxin plus | Ibumol | Natrafen Plus | Subridon;
  • (EC) Ecuador: Algitrin | Dolo octirona | Efficol plus | Finalin artritis | Finalin fem | Ibumedica | Paralgen plus forte;
  • (EE) Estonia: Combogesic;
  • (EG) Egypt: Cetafen | Megafen | Parofen;
  • (ES) Spain: Dolostop plus;
  • (GB) United Kingdom: Combogesic | Nuromol | Nuromol double action;
  • (GH) Ghana: Combipar;
  • (GR) Greece: Gopain | Ibutomol | Unitek;
  • (HK) Hong Kong: Maxigesic;
  • (HR) Croatia: Lekofen | Neofen combo;
  • (HU) Hungary: Brufen plus;
  • (ID) Indonesia: Aknil | Axalan | Bimacyl | Exedra rema | Iremax | Limasip | Linugo | Neo rheumacyl | Oskadon sp | Parafen | Paramex nyeri otot | Prafenta;
  • (IE) Ireland: Easolief duo;
  • (IL) Israel: Combodex;
  • (IN) India: Acegesic | Actimol f | Adiflam plus | Anaflam | Answell | Antiflam | Arcure | Arden plus | Arfen comp | Arfen-p | Arpibru | Artifen plus | Artigesic | Bestofen | Bestogesic plus old | Biobru plus | Bren plus | Bruace | Brucet | Bruceta | Brufamol | Brufamol plus | Brufen p | Bruforte | Brugesic p | Brupal | Brustan | Brustin | Bufex | Cadotryl | Calpol plus | Combiflam | Combiforex | Corflam | Credol-a | Creflam | Crofen | Curegesic | Curiflam forte | Deflam | Dip | Dolgesic | Dolomed | Doloprofen | Dolosans | Dt ibuflam | Duoflam | Eldoflam-old | Embru plus | Emflam-plus | Eucrafen | Extragesic | Fenceta | Fenmol | Fenomol | Fentrex plus | Flexon | Flyon | Geeflam | Gexofen | Iben | Iben plus | Ibu-p libra | Ibubid plus | Ibuclin | Ibucon plus | Ibudex | Ibudol-A Kid | Ibufen plus | Ibuflamar-p | Ibugesic plus | Ibumag plus | Ibumet-p | Ibumol | Ibunij a tab. | Ibunol | Ibupar | Ibupil | Ibuplus | Iburic plus | Ibusaan | Ibuspan-p | Ibustal Plus | Ibusule | Ibuter | Ibuwin | Imol | Inflake | Inflazen | Inflazen-m | Inpane | Intaflam | Itnil | Jk flam | Lederflam plus | Lupiflam | Magadol | Maxofen | Maxofen plus | Medomol plus | Mexipar | Multigon | Neurophen forte | New artifen plus | Nivafen | Norswel plus | Nostafen | Orthogesic | Osofen plus | Osyfen | Osyfen plus | P fen | Pabuflam | Pacitab | Parbudol | Pd flam | Pinkin plus | Prenovil | Prestigin plus | Procider ef | Profentol | Pyreflam | Pyremol-ib | Redflam | Reduc-a | Reducin-a | Regaflam | Relifen plus | Relpa | Renofen | Rubigesic-p | Safeaid | Stifnil | Tolfen | Torynal | Tribusynth | Triflam | Tylofen | Velcomb | Windol | Xeroflam | Zupar;
  • (IT) Italy: Tabumol | Tachifene;
  • (JO) Jordan: Bigesic | Ibumol | Taskine pain;
  • (JP) Japan: Norshin ai;
  • (KE) Kenya: Abumol | Artifen plus | Betafen plus | Brupal forte | Brupal kid | Brustan | Cetafen | Combisun | Fenpar | Fenplus | Finmol | Flexon | Ibuflam plus | Ibulab | Ibupar | Ibuplus | Nauma plus | Paraconica plus | Paraflam | Relievo | Relpa;
  • (LB) Lebanon: Maxifen;
  • (LT) Lithuania: Ibuclin | Metafenex;
  • (LU) Luxembourg: Nuralgan;
  • (LV) Latvia: Combogesic | Ibuclin | Metafenex;
  • (MX) Mexico: Acciogen | Algitrin | Dualgos | Proxego;
  • (MY) Malaysia: Maxigesic;
  • (NG) Nigeria: Dyofen | Lotemp plus | Zedfen plus;
  • (NL) Netherlands: Nuralgan;
  • (NO) Norway: Dolerin;
  • (NZ) New Zealand: Brufen extra | Maxigesic | Nuromol | Paracare paracetamol + ibuprofen | Paracetamol + ibuprofen | Pharmacy health paracetamol & ibuprofen;
  • (PE) Peru: Calmiren | Dolmigran | Dolo octirona lch | Dolomarket plus | Dolomax plus | Dolomolargesico | Thermoflam;
  • (PH) Philippines: Alaxan | Aldrinex | Brustan | Cortal pain | Cortal Sqr | Femol | Fenpar | Mulax | Muskelax | Parabufen | Parafen | Paramax | Proflex | Relaxid | Restolax | Scheelax | Selxan;
  • (PK) Pakistan: Provas duo;
  • (PL) Poland: Apap intense | Nurofen Ultima;
  • (PR) Puerto Rico: Advil dual action;
  • (PT) Portugal: Brufenon | Dolostop duo | Duodix | Trifeduo;
  • (PY) Paraguay: Dolo feminal | Duomax | Kitadol plus | Libredol plus;
  • (RO) Romania: Analgex | Biofen extra | Combifexin | Paduden duo | Synocam;
  • (RU) Russian Federation: Brustan | Hirumat | Ibuclin | Next | Nuralgon | Nurofen long | Nurofen multisymptom;
  • (SE) Sweden: Dolerin;
  • (SG) Singapore: Maxigesic | Nuromol;
  • (SI) Slovenia: Adobil | Ibuprofen/paracetamol belupo | Lekofusin | Metafen;
  • (SK) Slovakia: Cetalgen;
  • (TH) Thailand: Alaxan pi tab | Bruno | Brustan | Dologen | Ibucet | Ibuman plus | Ibutamol | Kintal-b | Lofen | Ostemed | Panofen | Parafen | Setargin 525 | Skelan | Torrafen | Torrafen forte;
  • (UA) Ukraine: Brustan | Darfen long | Ibuclin | Inflagesik Plus | Lekadol long | Noxapan | Nurofen intensive | Nurofen long | Tarafol;
  • (UG) Uganda: Astraflam | Brustan | Combifen | Ibumol | Ibupar | Primafen;
  • (UY) Uruguay: Doblon | Dolo octirona | Perifar Plus;
  • (VN) Viet Nam: Agiparofen | Doaxan s | Dolanol | Fencedol | Medialeczan | Paralmax pain | Protamol | Richaxan;
  • (ZA) South Africa: Ibumol | Maxigesic | Mypaid | Nocomypro;
  • (ZM) Zambia: Adiflam plus | Brupal | Brustan | Ibugesic plus | Ibun | Panado plus
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