Drug Interaction Report

Acetaminophen And Codeine and Norethindrone: Interaction Details

AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Acetaminophen And Codeine

Capital® & Codeine Codrix® Empracet® (#3, #4) Papa-deine® (#3, #4) Phenaphen® with Codeine (#2, #3, #4) Proval® #3 Tylenol with Codeine Tylenol® with Codeine (#3, #4)
+

Norethindrone

Aygestin Gallifrey
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jun 30, 2026
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Interaction severity
Moderate
Can be significant — usually manageable with monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 489 documented Acetaminophen And Codeine interactions, 26 are rated moderate — including this one.
At a glance Theoretical Effects may be weaker Effects may be stronger
The Bottom Line
This is a theoretical, moderate interaction: your birth control pill may slightly lower acetaminophen's effect while its estrogen level may run a bit higher. Keep taking both as prescribed and mention any reduced pain relief or estrogen-related side effects to your care team.

You're taking a pain medicine that combines acetaminophen (Tylenol) with codeine, along with a birth control pill that contains estrogen and norethindrone. These two can gently affect each other's levels in the body.

The acetaminophen may work a little less strongly because the pill can lower its levels. At the same time, the estrogen from your pill may build up a bit higher, which could slightly raise the chance of estrogen-related side effects. This is based mostly on theory, not strong real-world data, so it's usually not a big worry. Your care team can easily keep an eye on this and adjust things if needed, so keep taking both as prescribed.

Effect: Combined oral contraceptives (ethinyl estradiol/norethindrone) may increase ethinyl estradiol exposure and reduce acetaminophen exposure.

  • Mechanism: Acetaminophen may competitively inhibit sulfate/glucuronide conjugation, raising EE plasma concentrations; conversely COCs induce acetaminophen conjugation, lowering its levels. Codeine is a prodrug, but is not the affected moiety here.
  • Direction/magnitude: Bidirectional, magnitude unquantified.
  • Onset: Unspecified. Evidence: Theoretical.
  • Management: No dosing change usually required; individualize and monitor analgesic efficacy and for estrogenic effects if clinically relevant.
Onset
unspecified
Evidence
theoretical
Severity
Moderate

What happens

Increased ethinyl estradiol exposure and reduced acetaminophen exposure

Interaction Deep Dive

Taking acetaminophen together with an oral combination contraceptive containing ethinyl estradiol and norethindrone may raise plasma levels of ethinyl estradiol, potentially through inhibition of conjugation. In addition, COCs have been demonstrated to lower plasma concentrations of acetaminophen1.

Why it happens (mechanism)

Inhibition of conjugation; unknown

How to manage this interaction

This is a theoretical interaction, so most people can keep taking both as prescribed. Here's how a care team typically handles it:

  • Your pain relief from the acetaminophen/codeine may be slightly reduced. Tell your prescriber if the pain medicine isn't controlling your pain as expected, since the dose may need to be adjusted and individualized by your team.
  • Estrogen levels from your pill may run a little higher, so your team may monitor you more closely for estrogen-related side effects.

Don't stop or change either medication on your own. Bring any questions about effectiveness or side effects to your pharmacist or doctor.

Management is individual — confirm any change with your pharmacist or prescriber.

Common questions

Can I take Acetaminophen And Codeine and Norethindrone together?

This is a theoretical, moderate interaction: your birth control pill may slightly lower acetaminophen's effect while its estrogen level may run a bit higher. Keep taking both as prescribed and mention any reduced pain relief or estrogen-related side effects to your care team. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Acetaminophen And Codeine and Norethindrone interaction?

It is rated moderate. Can be significant — usually manageable with monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How is the Acetaminophen And Codeine and Norethindrone interaction managed?

This is a theoretical interaction, so most people can keep taking both as prescribed. Here's how a care team typically handles it: Your pain relief from the acetaminophen/codeine may be slightly reduced. Tell your prescriber if the pain medicine isn't controlling your pain as expected, since the dose may need to be adjusted and individualized by your team. Estrogen levels from your pill may run a… Management is individual — always follow your own care team's guidance.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Acetaminophen And Codeine or Norethindrone need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there anything you'd monitor while I'm on both?

References (1)

  1. Product Information: LOESTRIN(R) 24 Fe oral tablets, norethindrone acetate ethinyl estradiol oral tablets, ferrous fumarate oral tablets. Teva Pharmaceuticals USA Inc (per FDA), Parsippany, NJ, 2023. DailyMed
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Beyond drug–drug

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.