Acetaminophen and ibuprofen

What Acetaminophen and ibuprofen is used for

Quoted from the “Indications and Usage” section of the FDA-approved label.

COMBOGESIC is indicated in adults for the short-term management of mild to moderate acute pain. COMBOGESIC is a combination of acetaminophen and ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), and is indicated in adults for the short term management of mild to moderate acute pain.

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. Read the full label on DailyMed →

Label quoted: the one for the most common form (tablet, film coated, oral), Combogesic, Preferred Pharmaceuticals Inc.; it covers 1 product in the FDA NDC Directory. The side effects, interactions, dosage and pregnancy quotes below come from this same label.

The FDA has 4 labels for products of this medicine (different makers and forms); uses can differ between them. Check the label that comes with your own medicine.

This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.

Boxed warning

A boxed warning (“black box”) is the FDA’s strongest warning on a drug label, for serious or life-threatening risks.

This label has a boxed warning. Its heading: WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK, AND GASTROINTESTINAL RISK WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK AND GASTROINTESTINAL RISK. Read it on the full label →

4 of 4 FDA labels for this medicine have a boxed warning.

Acetaminophen and ibuprofen boxed warning: what the label says

Quoted from the boxed warning of the FDA-approved label.

WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK, AND GASTROINTESTINAL RISK WARNING: HEPATOTOXICITY, CARDIOVASCULAR RISK AND GASTROINTESTINAL RISK See full prescribing information for complete boxed warning.

• COMBOGESIC contains acetaminophen, which has been associated with cases of acute liver failure, at times resulting in liver transplant and death.

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Most of the cases of liver injury are associated with doses of acetaminophen that exceed 4,000 milligrams per day, and often involve more than one acetaminophen containing product (5.1).

• Nonsteroidal anti-inflammatory drugs (NSAIDS), like the ibuprofen in COMBOGESIC, cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (5.2).
• COMBOGESIC tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (5.2).
• NSAIDS, like the ibuprofen in COMBOGESIC, cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events (5.3). HEPATOTOXICITY COMBOGESIC contains acetaminophen. Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product [see Warnings and Precautions (5.1)]. CARDIOVASCULAR RISK COMBOGESIC contains ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use [see Warnings and Precautions (5.2)]. COMBOGESIC is contraindicated for treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.2)]. GASTROINTESTINAL RISK NSAIDS cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings and Precautions (5.3)].

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. Read the full label on DailyMed →

Acetaminophen and ibuprofen side effects

Quoted from the “Adverse Reactions” section of the FDA-approved label. Tell your doctor about any side effect that worries you.

The following clinically significant adverse reactions to ibuprofen or acetaminophen are described elsewhere in other sections of the labelling.

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• Hepatotoxicity [see Warnings and Precautions (5.1)]
• Cardiovascular Thrombotic Events [see Warnings and Precautions (5.2)]
• Gastrointestinal Bleeding, Ulceration, and Perforation [see Warnings and Precautions (5.3)]
• Hypertension [see Warnings and Precautions (5.4)]
• Heart Failure and Edema [see Warnings and Precautions (5.5)]
• Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6)]
• Anaphylaxis and Other Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
• Serious Skin Reactions [see Warnings and Precautions (5.9)]
• Hematologic Toxicity [see Warnings and Precautions (5.12)] The most common adverse reactions (incidence of ≥ 2% for patients receiving COMBOGESIC) are: nausea, vomiting, headache, dizziness, somnolence, post-procedural hemorrhage, and swelling of the face (Table 1). The most common adverse reactions (greater than or equal to 2%) are nausea, vomiting, headache, dizziness, somnolence, post-procedural hemorrhage, and swelling of the face (6). To report SUSPECTED ADVERSE REACTIONS, contact AFT Pharmaceuticals US, Inc at 01-248-631-4810 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to the rates reported from clinical trials of another drug and may not reflect the rates observed in practice. The clinical trials of COMBOGESIC have been conducted in patients with postoperative pain following dental and arthroscopic procedures, who received double-blind treatment every 6 hours for 24 or 48 hours. Most commonly (≥2%) reported adverse reactions by organ system during double-blind treatment are listed in the table below. Adverse reactions are closely related to the extent (the level and length) of exposure. The incidences of overall and individual adverse reactions reported during the double-blind treatment period did not suggest an increase of risks associated with short-term (up to one or two days) use of the combination drug, COMBOGESIC in comparison to each individual component, acetaminophen or ibuprofen, and to placebo.

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. This is part of the section. Read the full label on DailyMed →

Acetaminophen and ibuprofen drug interactions

Quoted from the “Drug Interactions” section of the FDA-approved label. Tell your pharmacist about every medicine, vitamin and herbal product you take.

Table 2: Clinically Significant Drug Interactions with COMBOGESIC Drugs That Interfere with Hemostasis Clinical Impact:

• Ibuprofen and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of ibuprofen and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.
• Serotonin release by platelets plays an important role in hemostasis.

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Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of COMBOGESIC with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see Warnings and Precautions (5.12)]. Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see Warnings and Precautions (5.3)]. Intervention: Concomitant use of COMBOGESIC and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see Warnings and Precautions (5.3)]. COMBOGESIC is not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact:

• NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).
• In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention:
• During concomitant use of COMBOGESIC and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
• During concomitant use of COMBOGESIC and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function [see Warnings and Precautions (5.6)].
• When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. This is part of the section. Read the full label on DailyMed →

Acetaminophen and ibuprofen dosage

Quoted from the “Dosage and Administration” section of the FDA-approved label. Your own dose is the one your doctor prescribes: do not change it on your own.

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)].
• Do not exceed the recommended dose of COMBOGESIC in 24 hours [see (2) below].
• Do not co-administer COMBOGESIC with other acetaminophen- or NSAID-containing products [see Warnings and Precautions (5.1, 5.2, 5.3)].

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The recommended dose of COMBOGESIC is 3 tablets every 6 hours as needed for pain relief, up to a maximum of 12 tablets per day.

• Use the lowest effective dosage for shortest duration consistent with individual patient treatment goals (2).
• Do not administer with other acetaminophen-containing products (2). Three tablets every 6 hours as needed for pain relief, up to a maximum of 12 tablets per day (2).

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. Read the full label on DailyMed →

Acetaminophen and ibuprofen in pregnancy

Quoted from the pregnancy part of the FDA-approved label. Ask your doctor before you take any medicine while pregnant or planning a pregnancy.

Risk Summary Ibuprofen Use of NSAID-containing products, including COMBOGESIC, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of COMBOGESIC use between about 20 and 30 weeks of gestation and avoid COMBOGESIC use at about 30 weeks of gestation and later in pregnancy (see Clinical Considerations, Data).

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Premature Closure of Fetal Ductus Arteriosus: Use of NSAID-containing products, including COMBOGESIC, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment: Use of NSAID-containing products, including COMBOGESIC, at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimester of pregnancy are inconclusive. In published animal reproduction studies, there were no clear developmental effects at doses up to 2.7-times the maximum human daily dose (MHDD) in the rabbit and 1.5-times in the MHDD rat when dosed throughout gestation. In contrast, an increase in membranous ventricular septal defects was reported in rats treated on Gestation Days 9 & 10 with 2.2-times the MHDD. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as ibuprofen, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. Acetaminophen Prolonged experience with acetaminophen in pregnant women over several decades, based on published observational epidemiological studies and case reports, did not identify a drug associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes (see Data). Reproductive and developmental studies in rats and mice from the published literature have identified adverse events at clinically relevant doses of acetaminophen. Fetotoxicity, increases in bone variations in the fetuses, and necrosis in the fetus liver and kidney have been noted in studies in rats. In mice treated with acetaminophen at doses within the clinical dosing range, cumulative adverse effects on reproduction were seen in a continuous breeding study. A reduction in number of litters of the parental mating pair was observed as well as retarded growth and abnormal sperm in their offspring and reduced birth weight in the next generation. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. This is part of the section. Read the full label on DailyMed →

When Acetaminophen and ibuprofen should not be used

Quoted from the “Contraindications” section of the FDA-approved label.

COMBOGESIC is contraindicated in:

• patients with a known hypersensitivity (e.g., anaphylactic reactions, serious skin reactions) to acetaminophen, ibuprofen, other NSAIDs, or to any of the excipients in this product [see Warnings and Precautions (5.7, 5.8, 5.9)].
• patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDS [see Warnings and Precautions (5.7 and 5.8)].

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• the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.2)]. COMBOGESIC is contraindicated in:
• patients with known hypersensitivity to acetaminophen, ibuprofen, other NSAIDs, or to any of the excipients in this product (4).
• patients with a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (4).
• the setting of coronary artery bypass graft (CABG) surgery (4).

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. Read the full label on DailyMed →

Acetaminophen and ibuprofen overdose

Quoted from the “Overdosage” section of the FDA-approved label. If someone may have taken too much, call Poison Help at 1-800-222-1222 (or 911 in an emergency).

COMBOGESIC is a combination product. The clinical presentation of overdose may include the signs and symptoms of acetaminophen toxicity, ibuprofen toxicity, or both. Acetaminophen The initial symptoms seen within the first 24 hours following an acetaminophen overdose are: anorexia, nausea, vomiting, malaise, pallor and diaphoresis. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

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In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects also may occur. Plasma acetaminophen levels >300 mcg/mL at 4 hours after oral ingestion were associated with hepatic damage in 90% of patients; minimal hepatic damage is anticipated if plasma levels at 4 hours are <150 mcg/mL or <37.5 mcg/mL at 12 hours after ingestion. If an acetaminophen overdose is suspected, obtain a serum acetaminophen assay as soon as possible, but no sooner than 4 hours following oral ingestion. Obtain liver function studies initially and repeat at 24-hour intervals. Administer the antidote N-acetylcysteine (NAC) as early as possible. As a guide to treatment of acute ingestion, the acetaminophen level can be plotted against time since oral ingestion on a nomogram Rumack-Matthew). The lower toxic line on the nomogram is equivalent to 150 mcg/mL at 4 hours and 37.5 mcg/mL at 12 hours. If serum level is above the lower line, administer the entire course of NAC treatment. Withhold NAC therapy if the acetaminophen level is below the lower line. Ibuprofen Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare [see Warnings and Precautions (5.1, 5.2, 5.3, 5.4, 5.6, 5.14)]. Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. It is advisable to contact a poison control center (1-800-222-1222) to determine the latest recommendations because strategies for the management of overdose are continually evolving. If gastric decontamination may benefit the patient, e.g., short time since ingestion or a large overdosage (5 to 10 times the recommended dosage), consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or an osmotic cathartic in symptomatic patients if clinically appropriate.

— FDA label: Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026. Read the full label on DailyMed →

Forms and how it is given

Same medicine, other forms and combinations

Prescription medicine pages on this site that share an active ingredient with this one, from the FDA NDC Directory. A combination is a different medicine: ask your pharmacist before you switch.

Other medicines with one of these active ingredients

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• Oxycodone and acetaminophenEndocet, Prolate · 136 products
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• Butalbital and acetaminophenTencon, Allzital · 16 products
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• Hydrocodone bitartrate and ibuprofen5 products
• Benzhydrocodone and acetaminophenApadaz · 3 products
• Acetaminophen, caffeine, dihydrocodeine bitartrateTrezix · 1 product

Companies that list this medicine

Labelers in the FDA NDC Directory: the company named on the package (maker or distributor), with the number of prescription products.

• Preferred Pharmaceuticals Inc.2 products
• Hikma Pharmaceuticals USA Inc.2 products
• AFT Pharmaceuticals US, Inc.1 product

FDA approval history

• NDA: New Drug Application: how a new (usually brand-name) medicine is approved.

Shortage status

The FDA drug shortage list does not show these products.

FDA Drug Shortages database →

Recalls

No recall linked to these products (by their NDC code) appears in the FDA enforcement reports.

Official identifiers

Next steps

• Find a pharmacy near youAsk which price applies to you and whether your product is affected by a recall
• Latest FDA drug recallsAll medicines, newest first
• Acetaminophen and ibuprofen sold over the counterDrug Facts label and store brands
• CombogesicBrand page: products, maker and price
• Combogesic IVBrand page: products, maker and price
• Preferred Pharmaceuticals Inc.Maker or distributor
• Hikma Pharmaceuticals USA Inc.Maker or distributor
• AFT Pharmaceuticals US, Inc.Maker or distributor
• All prescription drugs A to ZSearch by generic, brand or Spanish name

Sources

1. FDA-approved label on DailyMed (National Library of Medicine) — Combogesic, Preferred Pharmaceuticals Inc., effective August 20, 2026; via openFDA, FDA data exported October 30, 2026, retrieved October 31, 2026
2. NDC Directory (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
3. Drugs@FDA (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
4. Drug recall enforcement reports (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 27, 2026, retrieved October 31, 2026
5. Drug shortages (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026

openFDA data is provided by the FDA as is; it may be incomplete. Always rely on the label that comes with your medicine. FDA Enforcement Report search →

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