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Acetaminophen/hydrocodone: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on March 31, 2023.

1. How it works

  • Acetaminophen/hydrocodone is a combination of two different pain-relieving 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. Hydrocodone is metabolized to hydromorphone (the active component) which binds to specific receptors known as opioid receptors that block pain signals on their way to the brain.
  • Acetaminophen/hydrocodone belongs to the group of medicines known as combination narcotic analgesics. It may also be called a combination opioid analgesic.

2. Upsides

  • May be used to relieve moderate-to-moderately severe pain unresponsive to other treatment options.
  • The combination is more effective than either drug alone.
  • Both drugs last for a similar length of time in the body which makes them appropriate to be given together.
  • Available in tablet and oral solution forms.
  • Has been FDA-approved for use in children; however, because of its high potential for addiction, acetaminophen/hydrocodone should only be given to children if there are no other alternatives.
  • Generic acetaminophen/hydrocodone is available.

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 (hydrocodone component). Avoid alcohol.
  • Nausea, vomiting, and constipation (laxatives may be required); shortness of breath; dizziness; and low blood pressure (hydrocodone component) are also common. Hydrocodone may be more likely to cause constipation than other opioids such as oxycodone.
  • 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.
  • Hydrocodone is habit-forming and potentially abusable. The combination of acetaminophen and hydrocodone should only be used short-term at the lowest effective dose when other nonopioid analgesics are not effective. Legitimate supplies of products containing hydrocodone may be sought out by drug seekers. Hydrocodone is one of the most abused opioids in the United States.
  • Abrupt discontinuation of any hydrocodone-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, a runny nose, sweating, muscle aches, insomnia, irritability, and gastrointestinal complaints. Babies born to mothers who are physically dependent on hydrocodone will also be physically dependent.
  • Rarely, serious, life-threatening, breathing problems may occur attributable to the hydrocodone component. The risk is greater with higher dosages of acetaminophen/hydrocodone, 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.
  • Several medication errors have been associated with this drug. Be careful when writing prescriptions to ensure the dosage is correct.

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

5. Tips

  • Short-term use only. Not recommended for long-term use.
  • Do not exceed the recommended dosage.
  • Call emergency services if you experience any breathing difficulties, wheezing, itching, or facial swelling.
  • 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.
  • Tell your doctor if you think you have become addicted to this combination drug.
  • Keep out of the reach of children and pets. Accidental ingestion, even just one tablet, can be fatal.

6. Response and effectiveness

  • Peak concentrations are usually reached within 1.5 hours. The length of time acetaminophen/hydrocodone lasts varies among individuals; but, in general, may last from 4 to 6 hours. Only take as directed by your doctor.

7. Interactions

Medicines that interact with acetaminophen/hydrocodone may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with acetaminophen/hydrocodone. 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/hydrocodone include:

  • antibiotics, such as 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
  • antimigraine agents such as sumatriptan
  • antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
  • any medication that may cause drowsiness, such as amphetamines, benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
  • buprenorphine
  • HIV medications such as ritonavir
  • muscle relaxants, such as cyclobenzaprine
  • naltrexone
  • other medications that are CYP3A4 or CYP2D6 inhibitors or inducers
  • pentazocine
  • rifampin.

Avoid drinking alcohol or taking illegal or recreational drugs while taking acetaminophen/hydrocodone.

Note that this list is not all-inclusive and includes only common medications that may interact with acetaminophen/hydrocodone. You should refer to the prescribing information for acetaminophen/hydrocodone 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/hydrocodone 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: March 30, 2023.