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Tylenol With Codeine: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on April 5, 2023.

1. How it works

  • Tylenol With Codeine is a combination tablet containing both acetaminophen and codeine. Acetaminophen and codeine are 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 cyclo-oxygenase (COX) enzyme, located mainly in the brain. Codeine is metabolized to morphine in the liver through liver enzymes such as CYP2D6. Morphine binds to specific receptors known as opioid receptors that block pain signals on their way to the brain.
  • Tylenol With Codeine belongs to the group of medicines known as combination narcotic analgesics.
  • The Tylenol With Codeine brand has been discontinued in the United States but other brands and generic acetaminophen and codeine are still available.

2. Upsides

  • May be used to relieve mild-to-moderately severe pain. Use is limited by the addiction and dependence potential of codeine; codeine can also cause constipation.
  • Some people find taking fixed-dose combination tablets easier to take than taking two different medicines.
  • Tylenol With Codeine is available as a generic under the name acetaminophen/codeine.

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:

  • Stomach upsets, drowsiness, constipation, headache, abdominal pain, or nausea (codeine component) are the most common side effects reported.
  • Drowsiness may impair a person's reaction time and affect their ability to drive or operate machinery (codeine component). Avoid alcohol.
  • Codeine is potentially addictive and may be sought out by drug misusers. Do not overuse Tylenol With Codeine. Tolerance can also develop to codeine's analgesic effect and codeine may no longer work at the prescribed dosage. Products containing codeine have also been misused and may be sought out by drug users.
  • Marked differences may exist in the analgesic effect provided by codeine due to genetic variations in the CYP 2D6 liver enzyme responsible for metabolizing codeine into morphine. Consider alternative analgesics if Tylenol With Codeine is not having the desired pain-relieving effect.
  • Rarely, serious, life-threatening, breathing problems may occur (attributable to the codeine component; the risk is increased with higher dosages). Children are more at risk of breathing problems associated with Tylenol With Codeine, especially those who are ultra-rapid metabolizers.
  • Contraindicated in children younger than 12 years and children younger than 18 years following a tonsillectomy or adenoidectomy. Avoid in children aged 12 through 18 with other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.
  • There is a risk of liver failure with acetaminophen, but this is rare. The risk is increased in children, people who take higher than recommended dosages of acetaminophen (dosages greater than 4000mg/day in adults), take it for prolonged periods, or who drink alcohol. Avoid taking extra acetaminophen when taking Tylenol With Codeine.
  • People who are ultra-fast metabolizers of codeine through CYP2D6 may be at risk of morphine toxicity. Babies exposed to breast milk of rapid codeine metabolizers who are taking Tylenol With Codeine are also at risk of morphine toxicity which may be fatal or life-threatening; symptoms include increased sleepiness, difficulty breastfeeding, breathing difficulties, or floppiness - seek urgent medical help if you notice these signs. Avoid taking Tylenol With Codeine if you are breastfeeding or pregnant.
  • Products containing opioids such as codeine are required by the FDA to have a REMS (Risk Evaluation and Mitigation Strategy) associated with them and healthcare providers are encouraged to complete a REMS-compliant education program, counsel patients or their caregivers with every prescription on the safe use, storage, disposal, and serious risks associated with these products, explain to patients the importance of reading the medication guide, and improve patient, household, and community safety.
  • Keep out of reach of children because accidental ingestion may result in a fatal overdose of Tylenol With Codeine. Babies who have been exposed to Tylenol With Codeine in the womb may experience neonatal opioid withdrawal syndrome when born. Monitor and treat accordingly.
  • Tylenol With Codeine may interact with several medications that are metabolized through the same liver enzymes CYP3A4 or CYP2D6. Profound sedation, breathing difficulties, and other adverse effects may result if benzodiazepines or similar drugs are given at the same time as codeine.
  • Tylenol With Codeine is a Schedule III controlled substance.

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

  • Tylenol With Codeine is an effective combination analgesic for the relief of mild-to-moderately severe pain. However, the codeine component can be addictive and it may also cause constipation and/or drowsiness.

5. Tips

  • May be taken with or without food.
  • Short-term use only (typically three days unless your doctor has told you to take it longer). Not recommended for long-term use.
  • May cause drowsiness which may impair reaction skills and affect your ability to drive or operate machinery (codeine component). Avoid alcohol.
  • Different strengths of Tylenol With Codeine are available. These are usually designated numbers (such as #2 or #3). Make sure you take the correct tablet and do not exceed the recommended dosage.
  • Seek urgent medical advice if you experience any breathing difficulties, wheezing, itching, or facial swelling.
  • Keep up your fluid and fiber intake to reduce the risk of developing constipation. Tell your doctor if you experience constipation and consider taking a laxative.
  • Tell your doctor if you think you have become addicted to this combination drug or if the usual dosage does not appear to be working.
  • Do not double up on other medications containing either acetaminophen or codeine while taking this combination product. Check product labels thoroughly to ensure these ingredients are not "hidden" in other products.

6. Response and effectiveness

  • Peak concentrations of codeine are reached within two hours and the analgesic activity of codeine lasts between four to six hours. Peak effects of acetaminophen (Tylenol) are reached within 30-60 minutes of administration and the analgesic effects of acetaminophen last between three and four hours.
  • About 70-80% of a dose of codeine is metabolized by the liver into several metabolites, some active and some inactive. One of these active metabolites is morphine. About 5-10% of codeine is metabolized into morphine by the hepatic enzyme, CYP2D6. Experts believe some of the analgesic properties of codeine are due to it being converted into morphine. Note that up to 10% of Caucasians, 6% of Mexican-Americans, and 5% of African-Americans are poor metabolizers at CYP2D6 and are unlikely to metabolize codeine into morphine. 30% of Ethiopians, 20% of Saudis, 10% of Portuguese and Greeks, and 4% of North Americans are ultra-rapid metabolizers at CYP 2D6 and may experience excessive side effects, such as extreme sleepiness, confusion, and shallow breathing, even with recommended dosages of Tylenol With Codeine.

7. Interactions

Medicines that interact with Tylenol With Codeine may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Tylenol With Codeine. 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 Tylenol With Codeine 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 hydrocodone, 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 Tylenol With Codeine.

Note that this list is not all-inclusive and includes only common medications that may interact with Tylenol With Codeine. You should refer to the prescribing information for Tylenol With Codeine 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 Tylenol With Codeine 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: April 5, 2023.