Tylenol With Rifampin Interaction

In our latest question and answer, the pharmacist discusses the interaction between Tylenol (acetaminophen) and rifampin.

Tylenol With Rifampin Interaction
Apr 19, 2019

Lynn asked

I am currently taking Ethambutol, Rifampin, and Azithromycin. Can I take Tylenol or Advil with this for back pain?

At a glance

  • Taking Tylenol (acetaminophen) with rifampin can increase the risk of livery injury.


Tylenol Bottle Pouring Out With Text - Tylenol With Rifampin

There is a potential interaction between Tylenol (acetaminophen) and rifampin.

Even though they can be used together in certain situations, there are a few things to be concerned about, including:

  • Tylenol may not be as effective.
  • There is an increased risk of hepatic (i.e. liver) side effects.

Interaction Mechanism

Rifampin is known to induce (i.e. increase the activity of) several liver metabolizing enzymes, notably CYP2E1 and CYP1A2.[1]

Acetaminophen is metabolized via many pathways in the body, including:[2]

  • Glucuronidation
  • Sulfate conjugation
  • CYP2E1 and CYP3A4 oxidation

CYP2E1 metabolism of acetaminophen produces the hepatotoxic (i.e. liver toxic) metabolite, N-acetyl-p-benzoquinoneimine (NAPQI).[3]

The formation of N-acetyl-p-benzoquinoneimine (NAPQI) isn't typically a concern when low, therapeutic doses of acetaminophen are used for short periods of time since it is further metabolized to non-toxic metabolites.

However, if high doses of acetaminophen are taken, or you have pre-existing liver disease, problems can arise.

Since rifampin increases the metabolizing activity of CYP2E1, there may be an increase in the risk for acetaminophen-induced liver toxicity since more N-acetyl-p-benzoquinoneimine (NAPQI) will be produced.

Additionally, Tylenol may not be as effective since it is being metabolized more quickly.

Other Concerns

Not only is the increased formation of N-acetyl-p-benzoquinoneimine (NAPQI) a concern, but rifampin on its own is associated with liver injury.

The prescribing information for rifampin states the following:[4]

"Rifampin has been shown to produce liver dysfunction. Fatalities associated with jaundice have occurred in patients with liver disease and in patients taking rifampin with other hepatotoxic agents. Patients with impaired liver function should be given rifampin only in cases of necessity and then with caution and under strict medical supervision."

Final Words

Having said all of the above, occasional use of Tylenol is sometimes safe to take with rifampin, as long as it is in low doses, for short periods of time.

Be sure to discuss your pain management options with your prescribing doctor to find the best therapy for you. They may recommend Tylenol if your liver function is normal or they may recommend something else, like an NSAID (e.g. Advil).

  1. ^ Rifampin drug interactions. PubMed
  2. ^ Elsevier ClinicalKey: Acetaminophen Monograph. ClinicalKey
  3. ^ N-acetyl-p-benzoquinone imine, the toxic metabolite of acetaminophen, is a topoisomerase II poison. PubMed
  4. ^ Rifampin Prescribing Information. AccessFDA

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