Tramadol and Acetaminophen (Oral)

Suitable for short term management of severe to moderate pain, tramadol and acetaminophen is a combination analgesic which can only be purchased with a prescription.


Tramadol and acetaminophen is a combination analgesic designed to treat pain.

Tramadol is an opioid analgesic (narcotic) and works on the central nervous system to change the way the body reacts to pain. It is a habit-forming drug, meaning that it can cause physical and mental dependency when used for a long time. Patients who use this drug for extended periods may notice physical withdrawal symptoms when they stop taking it. For this reason, tramadol and acetaminophen is only designed for short term use, such as to relieve pain following an injury or surgery.

Acetaminophen is a painkiller which can also help to reduce fever. Its mechanism of action isn't fully understood, but it is thought that it reduces the production of prostaglandins, which are chemicals which cause pain and inflammation. Essentially, acetaminophen works by increasing an individual's pain threshold, which means that they can sustain higher degrees of pain before they feel the discomfort. In regard to reducing fever, it works by manipulating the parts of the brain which regulate heat in order to force the body to reduce its temperature. It isn't a habit-forming drug and therefore doesn't pose the risk of physical or mental dependency. However, extended use and large doses can lead to liver damage, which is why the drug is only suitable for short term use.

When tramadol and acetaminophen are combined, they can more efficiently relieve pain and fever than when used separately.

In the US, tramadol and acetaminophen is known under the brand name Ultracet, while in Canada its brand name is Tramacet. It is administered in tablet form and is only available with a doctor's prescription; it cannot be purchased over-the-counter (OTC).

Condition(s) treated?

  • Pain
  • Fever

Type of medicine?

  • Analgesic (painkiller)
  • Antipyretic (fever reducer)

Side Effects

There are very many side effects of tramadol and acetaminophen use, many of which are extremely dangerous. It's vital that you familiarize yourself with them so that you recognize when it may be necessary to seek emergency care.

Allergic reaction

Allergic reaction to tramadol and acetaminophen can be extremely dangerous. If you notice any of the signs of allergic reaction listed below, stop taking the drug immediately and seek urgent medical care:

  • Blistering, peeling or loosening of the skin
  • Red lesions
  • Severe acne
  • Severe rash
  • Sores or ulcers on skin or in the mouth
  • Fever or chills
  • Swelling of the lips, tongue or throat

Respiratory depression

Respiratory depression is associated with the use of opioids including tramadol and acetaminophen, even when normal, recommended dosing is adhered to. If not treated immediately, respiratory depression can lead to respiratory arrest and it can be fatal. The risk is greatest during the first 24 to 72 hours of starting the medication. Always follow the dosing instructions given by your doctor and familiarize yourself with the symptoms of respiratory depression, which include:

  • Unusual tiredness and lethargy
  • Shortness of breath
  • Slow or shallow breathing
  • ¬†Depression
  • ¬†Blue or pale lips, fingers and toes
  • Confusion
  • Headaches
  • Seizures

Adrenal insufficiency

Opioids can lead to adrenal insufficiency, a condition which can be fatal if left untreated. In most cases, adrenal insufficiency has only occurred after use of opioids for longer than one month. Since tramadol and acetaminophen should only be used for up to five days, the risk of adrenal sufficiency is low. However, if you notice any of the following symptoms report them to your doctor urgently:

  • Dizziness
  • Fatigue
  • Low appetite
  • Low blood pressure
  • Nausea
  • Vomiting
  • Weakness

Dry mouth

It's relatively common for analgesics like tramadol and acetaminophen to cause dry mouth. Ice chips or sugarless gum or candy may help you to relieve this side effect. However, if the dryness continues, consult your dentist. Persistent dry mouth can increase the risk of teeth decay, gum disease and fungal infections in the mouth and therefore should not be ignored.

Serious side effects

Some side effects of tramadol and acetaminophen use are severe and require urgent medical care. This includes:

  • Dizziness
  • Burning, itching or redness of the skin
  • Swelling of eyelids, face, lips or tongue
  • Hive-like swellings or red lesions on skin
  • Sores or white spots in mouth or on lips
  • Red, irritated eyes
  • Fast heartbeat
  • Chest pain
  • Cough
  • Shortness of breath, tightness in chest or wheezing
  • Difficulty swallowing
  • Sore throat
  • Seizures
  • Vomiting
  • Vomiting blood or a substance that looks like coffee grounds
  • Diarrhea
  • Joint or muscle pain

Minor side effects

Some side effects are less serious and do not require medical attention. Often, they go away after the body adjusts to the medication, or they're mild enough that the pain-relieving benefits of the drug outweigh the inconvenience of the side effects. However, if they are persistent and have a significant impact on you, consult your doctor. There may be alternative treatments available, or you may be able to adjust some lifestyle factors to prevent or reduce the side effects.

  • Acidic or sour stomach
  • Stomach discomfort or pain
  • Belching
  • Bloating
  • Excess gas
  • Heartburn and indigestion
  • More frequent bowel movements
  • Soft or loose stools
  • Constipation
  • Difficult or painful urination
  • Urinating less frequently or in smaller quantities
  • Flushing of skin on face, neck, arms and upper chest
  • Dry mouth
  • Increased sweating
  • Cold sweats
  • Blurred vision or change in vision
  • Dizziness or faintness when getting up from sitting or lying
  • Sense of self or environment constantly moving
  • Sensation of spinning
  • Fainting
  • Abnormal or confused thinking
  • Anxiety
  • Depression
  • Dysphoria (sense of dissatisfaction or unease)
  • Euphoria
  • Paranoia
  • Crying or feeling more emotional
  • Mood swings or emotional overreactions
  • Loss of sense of reality
  • Morbid dreaming
  • Reduced sex drive
  • Memory problems
  • Unusual sleepiness or drowsiness
  • Clumsiness or issues with coordination or muscle control
  • Shakiness or feeling unsteady
  • Mild weakness or loss of energy
  • Muscle pain or weakness
  • Numbness or tingling sensation in feet, legs and hands
  • Muscle contractions or spasms
  • Weight loss
  • Headache
  • Ringing or buzzing in ears
  • Pounding in ears
  • Rapid, pounding or irregular heartbeat
  • Feeling unusually cold
  • Shivering

If you notice any other side effects not listed here, consult your doctor or report the side effects to the FDA.

Symptoms of overdose

Overdose of tramadol and acetaminophen could be life threatening. If you notice any of the following symptoms in yourself or in someone who is taking tramadol and acetaminophen, get emergency help:

  • Severe stomach or abdominal pain
  • Nausea
  • Vomiting blood
  • Black, tarry stools
  • Light colored stools
  • Dark urine
  • Chest pain
  • Insomnia
  • Disorientation
  • Extreme drowsiness
  • Extreme lethargy
  • Lightheadedness
  • Fever
  • Headache
  • Slow, fast, irregular or shallow breathing
  • Loss of appetite
  • Extreme changes in mood or behavior
  • Yellow skin or eyes
  • Pale or blue skin, fingernails or lips
  • Hallucinations (seeing or hearing things that aren't there)
  • Unpleasant odor on breath


Each tramadol and acetaminophen tablet contains 37.5 mg tramadol and 325 mg acetaminophen. Adults are usually recommended to take two tablets every four to six hours for up to five days. You should never take more than eight tablets within one day. If you feel that you don't need the tablets as frequently as every four to six hours, you don't have to take them and can simply take them as needed, provided that you do not take the medication for longer than five days.

If you miss a dose of tramadol and acetaminophen, take it as soon as you remember unless it is almost time for your next dose. In these instances, simply skip the dose and take the next one according to your usual schedule. Do not double doses to make up for those missed, as doing so could increase the risk of side effects or result in overdose.

Dose adjustments for renal impairment

Patients with reduced renal function are at an increased risk of side effects when taking tramadol and acetaminophen. Those with renal impairment should have creatinine levels monitored before being prescribed the drug. Patients with creatinine clearances of 30 mL/min or less should consume no more than two tramadol and acetaminophen tablets every 12 hours.

Dosages for pediatrics

Children over the age of 12 may be prescribed tramadol and acetaminophen, but this may be in much smaller doses to those usually administered to adults. Doctors will decide the appropriate dosage on a case by case basis.


There are many drug and medical interactions with tramadol and acetaminophen. Be sure that your doctor is aware of your medical history and knows about all other drugs that you currently take, no matter if prescribed or bought over-the-counter.

CNS depressants

Use of central nervous system (CNS) depressants, such as benzodiazepines (sedatives), muscle relaxants, anti-psychotics and tranquilizers increase the risk of respiratory depression when taken at the same time as tramadol and acetaminophen. Usually, the concurrent use of CNS depressants and tramadol and acetaminophen should be avoided. If alternative painkillers aren't available, doctors may continue to prescribe tramadol and acetaminophen at lower dosages, or they may adjust the dosage of the CNS depressants already being taken.

Patients who do take CNS depressants and tramadol and acetaminophen at the same time should take extra care to familiarize themselves with the symptoms of respiratory depression, such as labored or shallow breathing, irregular or slow heart rate and blue or pale lips and fingernails.

Serotonergic drugs

Although rare, there have been instances of serotonin syndrome in patients who take serotonergic drugs at the same time as tramadol and acetaminophen. Serotonergic drugs include:

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs)
  • Tricyclic antidepressants (TCAs)
  • Triptans
  • 5-HT3 receptor antagonists
  • Drugs which affect serotonergic neurotransmitter system, such as mirtazapine and tramadol
  • Drugs which impair serotonin metabolism such as linezolid and MAO inhibitors

Patients who take serotonergic drugs should familiarize themselves with the symptoms of serotonin syndrome before taking tramadol and acetaminophen, which include:

  • Agitation
  • Hallucinations
  • Coma
  • Hyperthermia
  • Tachycardia (rapid heart rate)
  • Nausea
  • Vomiting
  • Diarrhea

If serotonin syndrome does occur, it is usually within the first few hours or days of beginning concurrent use. If it is suspected, the use of tramadol and acetaminophen should be immediately discontinued.

Alcohol use

Alcohol is a central nervous system depressant and therefore increases the risk of respiratory depression in those taking tramadol and acetaminophen. Furthermore, alcohol can worsen drowsiness, a minor side effect often experienced with this medicine. Alcohol should therefore be avoided at all times when taking the drug.

MAO inhibitors

Tramadol and acetaminophen should not be taken at the same time as monoamine oxidase inhibitors (MAOIs) or within the last 14 days of taking MAOIs. This is because the drugs can increase the risk of seizures and serotonin syndrome.

MAOIs are typically prescribed to treat depression and include the following:

  • Isocarboxazid (Marplan)
  • Phenelzine (Nardil)
  • Selegiline (Emsam)
  • Tranylcypromine (Parnate)


The risk of having seizures when taking tramadol and acetaminophen is dramatically increased in patients who are concurrently taking the following medicines:

  • SSRIs, SNRIs, TCAs and antidepressants
  • Anorectics (appetite suppressants)
  • Other opioids
  • MAO inhibitors
  • Neuropleptics

There is also an increased risk of seizures in patients who are already at risk of seizures due to:

  • Epilepsy
  • Head trauma
  • Metabolic disorders
  • Alcohol and drug withdrawal
  • Central nervous system infections

Excessive acetaminophen intake

Acetaminophen can cause acute liver failure when taken in high doses. It is extremely important to avoid taking other medications that contain acetaminophen at the same time as tramadol and acetaminophen tablets. Patients may do this accidentally if they are attempting to get more relief from pain or if they unknowingly take other medications which contain the drug.

If taking other medicines, particularly over-the-counter medicines which you may not have discussed with your doctor, be sure to read the packaging and look out for acetaminophen or APAP. It is safest to avoid taking such medications completely, but particularly if your total consumption of acetaminophen will exceed 4,000 mg in one day. If you do realize that you've ingested more than 4,000 mg, seek urgent medical care even if you don't notice side effects and feel well.

Interactions with cytochrome P450 2D6 and cytochrome P450 3A4 inhibitors

Use of cytochrome P450 2D6 and cytochrome P450 3A4 inhibitors at the same time as tramadol and acetaminophen can increase the concentration of tramadol in the blood, which may increase the risk of serious side effects. Discontinuing such drugs before the use of tramadol and acetaminophen may also increase the risk of side effects. Doctors are likely to closely monitor patients in these circumstances.

Examples of P450 2D6 and cytochrome P450 3A4 inhibitors include:

  • Amiodarone
  • Quinidine
  • Macrolide antibiotics such as erythromycin
  • Azole-antifungal agents such as ketoconazole
  • Protease inhibitors such as ritonavir


Tramadol and acetaminophen is approved by the FDA for use of up to five days only. Continuing the use of this drug after five days increases the risk of physical and mental dependency, and could lead to withdrawal symptoms when use of the drug is subsequently ceased. If dependency is a risk, dosage of the drug should be gradually tapered off rather than being stopped abruptly.

Risk of addiction, misuse or abuse

Doctors will assess the individual risk of each patient for abuse or addiction when considering whether to prescribe tramadol and acetaminophen. Patients with a history of drug abuse and addiction, both of prescribed and street drugs, may be more likely to misuse it. In some instances, alternative painkillers which are not habit-forming may be prescribed instead. In others, doctors may opt to prescribe tramadol and acetaminophen in the lowest quantities possible and they may adopt more intensive monitoring practices in order to look out for signs of addiction or misuse.

Patients with a history of mental illness, particularly if they have demonstrated signs of self-harming behaviors or suicidal ideation, may not be suitable candidates for tramadol and acetaminophen use due to the risk of addiction and misuse, as well as the risk of depression as a side effect. Caution must also be taken when prescribing tramadol and acetaminophen to patients who are taking central nervous system depressants for mental health conditions, such as tranquilizers for insomnia and anti-anxiety medications, or SSRIs for depression.

Preexisting liver disease

Acetaminophen is strongly associated with liver disease, and individuals with underlying liver disease are at a higher risk of acute liver failure when they take tramadol and acetaminophen. If risk of liver disease appears to be particularly high, doctors may consider alternative painkillers which do not contain acetaminophen. If you have a medical history of liver problems, make sure your doctor knows.

Pediatric use

Tramadol and acetaminophen is contraindicated for children under the age of twelve because the risk of respiratory depression in this age group is much higher. For children over the age of 12, the drug may be prescribed at the lowest effective dose possible and for the shortest period of time possible. It should not be given to children who have an increased risk factor due to other medical conditions, such as:

  • Obesity
  • Sleep apnea
  • Pulmonary disease
  • Neuromuscular disease

It's also unsuitable for children who are already being treated with other medications which increase the risk of respiratory depression.

The drug is not suitable for managing post-operative pain in children under the age of 18 following tonsil or adenoid removal. This is because the risk of respiratory depression could be worsened by recent surgeries on the airways.

Renal impairment

Individuals with reduced renal function are at an increased risk of side effects when taking tramadol and acetaminophen. This is because the drug will be processed and eliminated from the body at a much slower rate than normal, which means it will remain in the body for much longer. Dosage should be greatly reduced for those with renal impairment; typically, they should take no more than two tablets every 12 hours. Doctors may also choose to monitor these patients more closely while they are taking the drug.

Pregnancy and breastfeeding

Tramadol and acetaminophen poses a risk to the fetus when taken by pregnant women. When the baby is born, it may suffer from opioid withdrawal syndrome which can be life threatening. For this reason, the drug should only be used during pregnancy if absolutely necessary and if the benefits to the mother far outweigh the risks to the fetus. If the drug must be used, it should be for the shortest period possible.

There have been instances of infant deaths occurring when the infants were breastfed from mothers who took tramadol and acetaminophen and were ultra-rapid metabolizers of morphine. Although very rare, the risk to nursing infants means that breastfeeding should not take place while the mother is taking tramadol and acetaminophen.

Interactions with other medical conditions

Tramadol and acetaminophen is unsuitable for those with severe bronchial asthma if they will be taking the drug in an unmonitored setting or without suitable resuscitative equipment available. This is because the drug poses a risk of respiratory depression, which may worsen the symptoms of asthma.

The risk of respiratory depression is also higher in patients who are elderly, cachetic or otherwise debilitated, as well as those with chronic pulmonary disease.

Patients with brain tumors, head injury, impaired consciousness or increased intracranial pressure may not be able to take tramadol and acetaminophen. This is because the drug could increase intracranial pressure and cause complications.

Those with gastrointestinal obstruction should not take tramadol and acetaminophen. It should be used with caution in patients which have biliary tract diseases such as acute pancreatitis since it may worsen symptoms.

Ability to complete hazardous activities

Since tramadol and acetaminophen can lead to drowsiness, sleepiness and lethargy, patients should avoid driving or operating machinery while taking the drug unless they know how it affects them.


Tramadol and acetaminophen should be stored in a closed container at room temperature. It shouldn't be exposed to moisture, heat or direct light. Avoid keeping the medicine in the bathroom where it may be exposed to humid conditions. Keep the medication from freezing.

The medicine may be extremely harmful to children and pets, so keep it up and away from the floor so that it is not within easy reach. Since the medicine is only available with a doctor's prescription it should only be taken by the person it was prescribed for. Never share the medication with someone else.

Do not take expired tramadol and acetaminophen. Instead, dispose of it safely according to the instruction of your healthcare provider. Do not keep unused medication and don't dispose of it in the household trash or by flushing it down the drain or toilet as it may be harmful to the environment.


Tramadol and acetaminophen is an analgesic designed to treat moderate to severe pain for up to five days. Tramadol is an opioid analgesic, also known as a narcotic, and works on the central nervous system. It is a habit-forming drug and can lead to physical dependency if used for a long period. Acetaminophen is a non-habit forming analgesic which can also help to reduce fever. Although it does not pose the risk of addiction, it is strongly associated with liver damage and is therefore unsuitable for long term use.

This drug frequently causes drowsiness, sleepiness, lethargy and dry mouth, all of which tend to be minor and don't require medical attention. More serious side effects include respiratory depression, adrenal insufficiency, liver damage, shortness of breath, rapid heartbeat and seizures. It can also cause mood changes and depression, and should therefore be used with caution in individuals with mental health problems.

In adults, the typical dosage of tramadol and acetaminophen is two tablets every six to eight hours, with no more than eight tablets being taken within one day. If a dosage is missed it can be taken as soon as remembered, unless it is almost time for the next dosage. In these cases, it is safest to wait until the next dosage and continue the schedule as normal. Doubling the dosages could result in worsened side effects or overdose.

Tramadol and acetaminophen should not be prescribed to children under the age of 12. It should be used with caution in pregnant women, children aged 12 to 18, people with liver damage and renal impairment, those at increased risk of respiratory depression or seizures, and individuals with a history of substance abuse. The drug interacts with serotonergic drugs and should not be taken with other drugs that contain acetaminophen.

Last Reviewed:
December 25, 2017
Last Updated:
April 05, 2018
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