Tramadol hydrochloride and acetaminophen

What Tramadol hydrochloride and acetaminophen is used for

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

Tramadol hydrochloride and acetaminophen tablets are indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Tramadol hydrochloride and acetaminophen tablets are indicated for short-term use of five days or less. …

— FDA label: Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 2026. Read the full label on DailyMed →

Label quoted: the one for the most common form (tablet, film coated, oral), Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy; 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 14 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. Read it on the full label →

11 of 14 FDA labels for this medicine have a boxed warning.

Tramadol hydrochloride and acetaminophen boxed warning: what the label says

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

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE and ACETAMINOPHEN Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride and acetaminophen exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1)].

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Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of tramadol hydrochloride and acetaminophen, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of tramadol hydrochloride and acetaminophen are essential [see Warnings and Precautions (5.2)]. Accidental Ingestion Accidental ingestion of even one dose of tramadol hydrochloride and acetaminophen, especially by children, can result in a fatal overdose of tramadol [see Warnings and Precautions (5.2)]. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of tramadol hydrochloride and acetaminophen and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3), Drug Interactions (7)]. NeonatalOpioidWithdrawal Syndrome (NOWS) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that managementbyneonatology experts will be available at delivery [see Warnings and Precautions (5.4)]. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings and Precautions (5.5)]. Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-Threatening Respiratory Depression in Children Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases occurred following tonsillectomy and/or adenoidectomy, and in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism [see Warnings and Precautions (5.6)]. Tramadol hydrochloride and acetaminophen is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. Avoid the use of tramadol hydrochloride and acetaminophen in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of tramadol [see Warnings and Precautions (5.6)].

— FDA label: Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 2026. This is part of the section. Read the full label on DailyMed →

Tramadol hydrochloride and acetaminophen 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 serious adverse reactions are discussed, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] Ultra-Rapid Metabolism of Tramadol and Other Risk Factors for Life-threatening Respiratory Depression in Children [see Warnings and Precautions (5.6)] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)] …

— FDA label: Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 2026. This is part of the section. Read the full label on DailyMed →

Tramadol hydrochloride and acetaminophen 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 includes clinically significant interactions with tramadol hydrochloride and acetaminophen.

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Table 2: Clinically Significant Drug Interactions with Tramadol Hydrochloride and Acetaminophen Tablets Inhibitors of CYP2D6 Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP2D6 inhibitors may result in an increase in the plasma concentration of tramadol and a decrease in the plasma concentration of M1, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride and acetaminophen is achieved. Since M1 is a more potent µ-opioid agonist, decreased M1 exposure could result in decreased therapeutic effects, and may result in signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol. Increased tramadol exposure can result in increased or prolonged therapeutic effects and increased risk for serious adverse events including seizures and serotonin syndrome. After stopping a CYP2D6 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease and the M1 plasma concentration will increase which could increase or prolong therapeutic effects but also increase adverse reactions related to opioid toxicity, and may cause potentially fatal respiratory depression [see Clinical Pharmacology (12.3)]. Intervention: If concomitant use of a CYP2D6 inhibitor is necessary, evaluate patients at frequent intervals for adverse reactions including opioid withdrawal, seizures and serotonin syndrome. If a CYP2D6 inhibitor is discontinued, consider lowering tramadol hydrochloride and acetaminophen dosage until stable drug effects are achieved. Evaluate patients at frequent intervals for adverse events including respiratory depression and sedation. Examples: Quinidine, fluoxetine, paroxetine and bupropion Inhibitors of CYP3A4 Clinical Impact: The concomitant use of tramadol hydrochloride and acetaminophen and CYP3A4 inhibitors can increase the plasma concentration of tramadol and may result in a greater amount of metabolism via CYP2D6 and greater levels of M1. Follow patients closely for increased risk of serious adverse events including seizures and serotonin syndrome, and adverse reactions related to opioid toxicity including potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of tramadol hydrochloride and acetaminophen is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the tramadol plasma concentration will decrease [see Clinical Pharmacology (12.3)], resulting in decreased opioid efficacy and possibly signs and symptoms of opioid withdrawal in patients who had developed physical dependence to tramadol.

— FDA label: Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 2026. This is part of the section. Read the full label on DailyMed →

Tramadol hydrochloride and acetaminophen 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.

Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with tramadol hydrochloride and acetaminophen tablets, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. (2.2, 5.1, 5.2, 5.3).

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Tramadol hydrochloride and acetaminophen tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. (2.1) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of tramadol hydrochloride and acetaminophen tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. (2.1, 5) Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. (2.1) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. (2.1, 5.1) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with tramadol hydrochloride and acetaminophen tablets. Consider this risk when selecting an initial dose and when making dose adjustments. (2.1, 5.2) Severe Renal Impairment: Do not exceed 2 tablets every 12 hours. (2.4) Periodically reassess patients receiving tramadol hydrochloride and acetaminophen tablets to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. (2.1) Do not use with other acetaminophen- or tramadol-containing products. (2, 5.20) Initiate treatment with in a dosing range of two tablets every 4 to 6 as needed for pain, and at the lowest dosage necessary to achieve adequate analgesia. Titrate the dosage based upon the individual patient’s response to their initial dose of tramadol hydrochloride and acetaminophen tablets; maximum of 8 tablets per day (2.3, 5) Do not rapidly reduce or abruptly discontinue tramadol hydrochloride and acetaminophen tablets in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. (2.5, 5.21) 2.1 Important Dosage and Administration Instructions Tramadol hydrochloride and acetaminophen tablets are not approved for use for more than 5 days. Do not exceed the recommended dose of tramadol hydrochloride and acetaminophen tablets.

— FDA label: Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 2026. This is part of the section. Read the full label on DailyMed →

When Tramadol hydrochloride and acetaminophen should not be used

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

Tramadol hydrochloride and acetaminophen tablets are contraindicated for: all children younger than 12 years of age [see Warnings and Precautions (5.6)] post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Warnings and Precautions (5.6)]. Tramadol hydrochloride and acetaminophen tablets are also contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.2)].

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Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.13)]. Patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.18)]. Previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids [see Warnings and Precautions (5.19)]. Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7)]. Children younger than 12 years of age (4) Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. (4) Significant respiratory depression. (4) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. (4) Known or suspected gastrointestinal obstruction, including paralytic ileus. (4) Previous hypersensitivity to tramadol hydrochloride, acetaminophen, any other component of this product, or opioids. (4) Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days (4)

— FDA label: Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 2026. Read the full label on DailyMed →

Tramadol hydrochloride and acetaminophen 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).

Clinical Presentation Tramadol hydrochloride and acetaminophen is a combination drug. The clinical presentation of overdose may include the signs and symptoms of tramadol toxicity, acetaminophen toxicity or both. The initial symptoms of tramadol overdosage may include respiratory depression and/or seizures. The initial symptoms seen within the first 24 hours following an acetaminophen overdose are: anorexia, nausea, vomiting, malaise, pallor and diaphoresis.

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Tramadol Acute overdosage with tramadol can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, QT prolongation, hypotension, partial or complete airway obstruction, atypical snoring, seizures, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2)]. Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication. Deaths due to overdose have been reported with abuse and misuse of tramadol [see Warnings and Precautions (5.1)]. Review of case reports has indicated that the risk of fatal overdose is further increased when tramadol is abused concurrently with alcohol or other CNS depressants, including other opioids. Acetaminophen In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia also 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. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. Treatment of Overdose A single or multiple drug overdose with tramadol and acetaminophen is a potentially lethal polydrug overdose. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Oxygen, intravenous fluids, vasopressors, assisted ventilation, and other supportive measures should be employed as indicated. Because strategies for the management of overdose are continually evolving, it is advisable to contact a poison control center (where available) to determine the latest recommendations for the management of an overdose. Tramadol In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures. For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene.

— FDA label: Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 2026. This is part of the section. 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

• Hydrocodone bitartrate and acetaminophenNorco · 208 products
• Oxycodone and acetaminophenEndocet, Prolate · 136 products
• Tramadol hydrochlorideConzip · 127 products
• Acetaminophen and codeine phosphate74 products
• Butalbital, acetaminophen and caffeineFioricet · 67 products
• Acetaminophen25 products
• Butalbital and acetaminophenTencon, Allzital · 16 products
• Butalbital, acetaminophen, caffeine and codeine phosphate8 products
• Acetaminophen and ibuprofenCombogesic, Combogesic IV · 5 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.

• Bryant Ranch Prepack3 products
• Asclemed USA, Inc.2 products
• Proficient Rx LP2 products
• Direct_Rx2 products
• AvPAK1 product
• St. Mary's Medical Park Pharmacy1 product
• Medsource Pharmaceuticals1 product
• Remedyrepack Inc.1 product
• Aurobindo Pharma Limited1 product
• Amneal Pharmaceuticals of New York LLC1 product
• Preferred Pharmaceuticals Inc.1 product

FDA approval history

• ANDA: Abbreviated New Drug Application: how a generic version is approved.

Generic approvals (3)

• ANDA090485Amneal Pharms · December 9, 2009
• ANDA201952Micro Labs Ltd India · December 14, 2012
• ANDA207152Aurobindo Pharma · March 22, 2017

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
• Tramadol/APAPBrand page: products, maker and price
• Bryant Ranch PrepackMaker or distributor
• Asclemed USA, Inc.Maker or distributor
• Proficient Rx LPMaker 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) — Tramadol Hydrochloride and Acetaminophen, St. Mary's Medical Park Pharmacy, effective June 30, 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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