Drug Interaction Report

Darifenacin and Acetaminophen And Codeine: 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)
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Darifenacin

Enablex
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jun 30, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close 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 23 documented Darifenacin interactions, 22 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
At a glance + Theoretical Effects may be stronger
The Bottom Line
Taking codeine with darifenacin can add up to worsen constipation and urinary retention, and rarely a near-stoppage of the bowel. Keep taking both as prescribed, but tell your care team right away about severe constipation, belly bloating, or trouble urinating.

Your pain medicine contains codeine, an opioid that naturally slows down your gut and can cause constipation. Darifenacin (Enablex) is a bladder medicine that also slows the gut and can make it harder to empty your bladder. When you take both, these slowing effects can add up.

In rare cases, the bowel can slow so much that it nearly stops. This is called paralytic ileus. Watch for hard constipation, a bloated or painful belly, or trouble urinating. The good news is this is manageable. Your care team can keep an eye on you and adjust things if needed, so let them know about any of these symptoms.

Effect: Additive anticholinergic and opioid effects on GI motility, increasing risk of severe constipation, urinary retention, and potentially paralytic ileus.

  • Mechanism: Codeine reduces GI motility via opioid receptors; darifenacin (an M3-selective antimuscarinic) further slows gut motility and impairs bladder emptying. Effects are additive (PD interaction).
  • Direction: Increased adverse GI/GU effects.
  • Evidence: Theoretical; severity rated major. Onset unspecified.
  • Management: Monitor for reduced bowel motility, abdominal distension, and urinary retention. Consider prophylactic bowel regimen; dose may be individualized by the care team.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

An increased risk of paralytic ileus

Interaction Deep Dive

Concomitant use of codeine with anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when codeine is used concomitantly with anticholinergic drugs1.

Why it happens (mechanism)

Additive effects on gastric motility

How to manage this interaction

You can usually take both medicines as prescribed, but your care team will want to watch for a slowed gut or bladder.

  • Keep taking both unless your prescriber tells you otherwise.
  • Tell your care team if you have hard constipation, a swollen or painful belly, no bowel movements, or trouble urinating.
  • Your team may monitor you more closely, suggest ways to keep your bowels moving (fluids, fiber, or a stool softener), or adjust and individualize your doses.

Seek prompt care for a very bloated, painful belly with no gas or stool, as this can signal a serious bowel slowdown.

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

Common questions

Can I take Darifenacin and Acetaminophen And Codeine together?

Taking codeine with darifenacin can add up to worsen constipation and urinary retention, and rarely a near-stoppage of the bowel. Keep taking both as prescribed, but tell your care team right away about severe constipation, belly bloating, or trouble urinating. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Darifenacin and Acetaminophen And Codeine interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

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

How is the Darifenacin and Acetaminophen And Codeine interaction managed?

You can usually take both medicines as prescribed, but your care team will want to watch for a slowed gut or bladder. Keep taking both unless your prescriber tells you otherwise. Tell your care team if you have hard constipation, a swollen or painful belly, no bowel movements, or trouble urinating. Your team may monitor you more closely, suggest ways to keep your bowels moving (fluids, fiber, or 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 Darifenacin or Acetaminophen And Codeine 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 a safer alternative to one of these medications for me?

References (1)

  1. Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
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Beyond drug–drug

These medications also interact with supplements

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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.