Medication Guide — Tramadol Hydrochloride And Acetaminophen

Patient-friendly FDA guidance and safety information.

Last updated · May 12, 2026Source: DailyMed ↗

Boxed Warning

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 .

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 .

Accidental Ingestion

Accidental ingestion of even one dose of tramadol hydrochloride and acetaminophen, especially by children, can result in a fatal overdose of tramadol .

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 .

NeonatalOpioidWithdrawal Syndrome (NOWS)

If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery .

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 .

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 . 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 . 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 .

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride and acetaminophen requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1 .

Hepatotoxicity

Tramadol hydrochloride and acetaminophen tablets contain tramadol hydrochloride and 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 .

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF TRAMADOL HYDROCHLORIDE and ACETAMINOPHEN

See full prescribing information for complete boxed warning.

Tramadol hydrochloride and acetaminophen exposes users to the risks of addiction, abuse and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing tramadol hydrochloride and acetaminophen, and monitor regularly for these behaviors or conditions. ( 5.1)
Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially during initiation or following a dose increase. ( 5.2)
Accidental ingestion of tramadol hydrochloride and acetaminophen, especially by children, can result in a fatal overdose of tramadol. ( 5.2)
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 for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. ( 5.3, 7)
Prolonged use of tramadol hydrochloride and acetaminophen, during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. ( 5.4)
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. ( 5.5)
Life-threatening respiratory depression and death have occurred in children who received tramadol. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of tramadol due to a CYP2D6 polymorphism ( 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 ( 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. ( 5.6)
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride and acetaminophen requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1. ( 5.7, 7)
Tramadol hydrochloride and acetaminophen tablets contain 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. ( 5.9)

Poison Help

If you suspect an overdose or accidental ingestion, call Poison Control: 1-800-222-1222 (free, 24/7, U.S.). For life-threatening symptoms, call 911.

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MEDICATION GUIDE

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Tramadol Hydrochloride and Acetaminophen Tablets USP CIV

(tram' a dol hye'' droe klor' ide and a seet'' a min' oh fen)

Tramadol hydrochloride and acetaminophen tablets are:

A strong prescription pain medicine that contains an opioid (narcotic) that is used for the short-term (five days or less) management of acute pain, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.
An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.

Important information about tramadol hydrochloride and acetaminophen tablets:

Get emergency help or call 911 right away if you take too much tramadol hydrochloride and acetaminophen (overdose). When you first start taking tramadol hydrochloride and acetaminophen tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Talk to your healthcare provider about naloxone, a medicine for the emergency treatment of an opioid overdose.
Tramadol hydrochloride and acetaminophen tablets can cause severe drowsiness, breathing problems (respiratory depression), coma and death when taken with benzodiazepines or other medicines that depress consciousness.
Never give anyone else your tramadol hydrochloride and acetaminophen tablets. They could die from taking it. Selling or giving away tramadol hydrochloride and acetaminophen tablets is against the law.
Store tramadol hydrochloride and acetaminophen tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home.
Get emergency help right away if you take more than 4,000 mg of acetaminophen in 1 day. Taking tramadol hydrochloride and acetaminophen tablets with other products that contain acetaminophen can lead to serious liver problems and death.

Important Information Guiding Use in Pediatric Patients:

Do not give tramadol hydrochloride and acetaminophen tablets to a child younger than 12 years of age.
Do not give tramadol hydrochloride and acetaminophen tablets to a child younger than 18 years of age after surgery to remove the tonsils and/or adenoids.
Avoid giving tramadol hydrochloride and acetaminophen tablets to children between 12 to 18 years of age who have risk factors for breathing problems such as obstructive sleep apnea, obesity, or underlying lung problems.

Do not take tramadol hydrochloride and acetaminophen tablets if you have:

Severe asthma, trouble breathing, or other lung problems.
A bowel blockage or have narrowing of the stomach or intestines.
An allergy to any of its ingredients (e.g., tramadol hydrochloride or acetaminophen).
Taken a Monoamine Oxidase Inhibitor, MAOI, (medicine used for depression) within the last 14 days.

Before taking tramadol hydrochloride and acetaminophen tablets, tell your healthcare provider if you have a history of:

head injury, seizures
problems urinating
abuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental health problems.
liver, kidney, thyroid problems
pancreas or gallbladder problems

Tell your healthcare provider if you are:

noticing your pain getting worse. If your pain gets worse after you take tramadol hydrochloride and acetaminophen tablets, do not take more of tramadol hydrochloride and acetaminophen tablets without first talking to your healthcare provider. Talk to your healthcare provider if the pain that you have increases, if you feel more sensitive to pain, or if you have new pain after taking tramadol hydrochloride and acetaminophen tablets.
pregnant or planning to become pregnant.Use of tramadol hydrochloride and acetaminophen tablets for an extended period of time during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated.
breastfeeding.Not recommended; it may harm your baby.
living in a household where there are small children or someone who has abused street or prescription drugs.
taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking tramadol hydrochloride and acetaminophen tablets with certain other medicines can cause serious side effects that could lead to death.

When taking tramadol hydrochloride and acetaminophen tablets:

Do not change your dose. Take tramadol hydrochloride and acetaminophen tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
For acute (short-term) pain, you may only need to take tramadol hydrochloride and acetaminophen tablets for a few days. You may have some tramadol hydrochloride and acetaminophen tablets left over that you did not use. See disposal information at the bottom of this section for directions on how to safely throw away (dispose of) your unused tramadol hydrochloride and acetaminophen tablets.
Take your prescribed dose: 2 tablets every 4 to 6 hours as needed for pain. Do not take more than your prescribed dose and do not take more than 8 tablets per day. If you miss a dose, take your next dose at your usual time.
Call your healthcare provider if the dose you are taking does not control your pain.
If you have been taking tramadol hydrochloride and acetaminophen tablets regularly, do not stop taking tramadol hydrochloride and acetaminophen tablets without talking to your healthcare provider.
Dispose of expired, unwanted, or unused tramadol hydrochloride and acetaminophen tablets by taking your drug to an authorized Drug Enforcement Administration (DEA)-registered collector or drug take-back program. If one is not available, you can dispose of tramadol hydrochloride and acetaminophen tablets by mixing the product with dirt, cat litter, or coffee grounds; placing the mixture in a sealed plastic bag and throwing the bag in your trash. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.

While taking tramadol hydrochloride and acetaminophen tablets DO NOT:

Drive or operate heavy machinery, until you know how tramadol hydrochloride and acetaminophen tablets affect you. Tramadol hydrochloride and acetaminophen tablets can make you sleepy, dizzy, or lightheaded.
Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with tramadol hydrochloride and acetaminophen tablets may cause you to overdose and die.

The possible side effects of tramadol hydrochloride and acetaminophen tablets:

constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help or call 911 right away if you have:

trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.

These are not all the possible side effects of tramadol hydrochloride and acetaminophen tablets. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov

Dispense with Medication Guide available at: www.aurobindousa.com/medication-guides

Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520

Manufactured by:
A urobindo Pharma Limited
Hyderabad-500 032, India

Revised: 01/2024

Sources

RxCUI: 836395

NDC: 45865-170

Last fetched: May 12, 2026

Source: DailyMed ↗

⚠️ Disclaimer

This information is for educational purposes only and is not medical advice. Always consult your doctor, pharmacist, or other licensed healthcare professional before starting, stopping, or changing any medicine. Read full medical disclaimer.