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Acetaminophen/oxycodone: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Dec 28, 2022.

1. How it works

  • Acetaminophen/oxycodone is a combination of two different pain-relief medicines with two different mechanisms of action.
  • Experts aren't sure exactly how acetaminophen works but suspect it blocks a specific type of cyclooxygenase (COX) enzyme, located mainly in the brain. Oxycodone binds to specific receptors known as mu opioid receptors that block pain signals on their way to the brain.
  • Acetaminophen/oxycodone belongs to the group of medicines known as combination narcotic analgesics. It may also be called a combination opioid analgesic.

2. Upsides

  • Effective for the management of moderate-to-moderately severe pain unresponsive to other treatment options.
  • The combination is more effective than either drug alone.
  • Available in tablet and oral solution forms, extended-release forms (Xartemis XR), as well as some cost-saving generic versions.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Drowsiness or dizziness that may impair reaction skills and affect a person's ability to drive or operate machinery (oxycodone component). Avoid alcohol.
  • Stomach upset including nausea and vomiting, and constipation (oxycodone component). Laxatives may be required.
  • Excessive dosages of acetaminophen can lead to liver injury or death. Care must be taken not to take additional acetaminophen from other sources.
  • Unlike NSAID pain relievers like ibuprofen, acetaminophen does not have any appreciable anti-inflammatory action.
  • The combination of acetaminophen and oxycodone is habit-forming and potentially abusable and should only be used short-term at the lowest effective dose when other nonopioid analgesics are not effective. Legitimate supplies of products containing oxycodone may be sought out by drug seekers.
  • Abrupt discontinuation of any oxycodone-containing medication in a person who has become physically dependent on it may lead to a withdrawal syndrome and symptoms such as restlessness, pupil dilation, watery eyes and a runny nose, sweating, muscle aches, insomnia, irritability, and gastrointestinal complaints. Babies born to mothers who are physically dependent on oxycodone will also be physically dependent.
  • Rarely, serious, life-threatening, breathing problems may occur attributable to the oxycodone component. The risk is greater with higher dosages of acetaminophen/oxycodone, in people with pre-existing respiratory disease, in seniors or the frail, or in those taking other medications that cause respiratory depression (such as benzodiazepines).
  • Interaction or overdosage may also cause serotonin syndrome. Symptoms include mental status changes such as agitation, hallucinations, coma, or delirium; a fast heart rate; dizziness; flushing; muscle tremor or rigidity; and stomach symptoms (including nausea, vomiting, and diarrhea).
  • May not be suitable for people with pre-existing respiratory depression or respiratory disease, with seizure disorders or a head injury, people with gastrointestinal obstruction, or recent use of monoamine oxidase inhibitors.
  • Not suitable for people younger than 18 years.
  • Long-term use of oxycodone has been associated with symptoms such as sexual dysfunction, an absence of periods, or infertility. Not recommended during pregnancy or while breastfeeding.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Acetaminophen/oxycodone may be used to relieve moderate-to-severe pain that is unrelieved by nonopioid analgesics; however, its use is limited by the dependence and addiction potential of the oxycodone component and the risk of respiratory depression (unusually slow and shallow breathing).

5. Tips

  • May be taken with or without food.
  • Take as directed by your doctor. Do not increase the dosage without his or her advice.
  • Call emergency services if you experience any breathing difficulties, wheezing, or facial swelling.
  • Tell your doctor if you think you have become addicted to this combination drug.
  • Short-term use is recommended. Do not exceed the prescribed dosage.
  • Tell your doctor if you have severe uncontrolled asthma, other breathing problems, or an intestinal blockage; you may not be able to use this medicine.
  • Call your doctor if you experience nausea or vomiting, stomach pain, itching, yellowing of your skin or eyes (jaundice), dark (brown) urine, or light-colored stools.
  • Keep out of reach of children and pets because even one dose of this combination narcotic can be fatal.
  • Avoid alcohol as the combination of alcohol and acetaminophen/oxycodone can increase side effects such as sedation and respiratory depression.
  • Xartemis XR is not interchangeable with other acetaminophen/oxycodone products because of differences in the frequency of administration.
  • Swallow extended-release acetaminophen/oxycodone (Xartemis XR) whole.
  • Do not cut, crush, chew or attempt to dissolve Xartemis XR because rapid release and absorption of a potentially fatal dose of oxycodone may occur.
  • Do not use during pregnancy and breastfeeding unless specifically recommended by your doctor.

6. Response and effectiveness

  • Oxycodone takes 1.8 hours to reach its maximum effect and its duration of activity lasts for 3-4 hours. Acetaminophen reaches its maximum effect within 30-60 minutes of administration and its analgesic effect lasts around 3 to 4 hours.

7. Interactions

Medicines that interact with acetaminophen/oxycodone may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with acetaminophen/oxycodone. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with acetaminophen/oxycodone include:

  • antibiotics, such as clarithromycin and erythromycin
  • antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
  • antifungal agents, such as itraconazole and ketoconazole
  • anticonvulsants, such as carbamazepine, lamotrigine, phenytoin, phenobarbital, or primidone
  • antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
  • any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
  • buprenorphine
  • busulfan
  • carbamazepine
  • dapsone
  • dasatinib
  • flucloxacillin
  • imatinib
  • isoniazid
  • migraine medications, such as almotriptan, eletriptan, or sumatriptan
  • muscle relaxants, such as cyclobenzaprine
  • rifampin
  • any other medication that inhibits hepatic enzymes CYP3A4 or CYP2D6 or induces CYP3A4
  • other medications that affect serotonin, such as amphetamines, fentanyl, lithium, tramadol, triptans (eg, almotriptan, eletriptan, or sumatriptan), or St. John's Wort.

Avoid grapefruit products and drinking alcohol or taking illegal or recreational drugs while taking acetaminophen/oxycodone.

Note that this list is not all-inclusive and includes only common medications that may interact with acetaminophen/oxycodone. You should refer to the prescribing information for acetaminophen/oxycodone for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use acetaminophen/oxycodone only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: December 28, 2022.