Acetaminophen And Codeine and Clopamide: 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
Clopamide
No brand names on record
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.
You've been prescribed a water pill (Clopamide) to help your body get rid of extra fluid and control your blood pressure. The codeine in your pain medicine may make that water pill work a little less well. That's because codeine can nudge your body to hold onto more water by releasing a hormone that tells your kidneys to keep fluid in.
In plain terms, you might notice you're not making as much urine, or your blood pressure and swelling aren't as controlled as usual. This is mostly a theoretical concern, so please don't worry or change anything on your own. Your care team can keep an eye on things and adjust your water pill if needed.
Effect: Codeine (opioid component) may reduce the diuretic efficacy of clopamide (a thiazide-like diuretic).
Mechanism: Opioid-mediated increase in antidiuretic hormone (ADH) release, promoting water retention and opposing the diuretic/antihypertensive effect. This is a PD interaction; neither agent's metabolism drives it.
- Direction: Reduced diuretic response.
- Onset: Unspecified.
- Evidence: Theoretical; severity rated major.
- Management: Monitor urine output, blood pressure, and volume status/edema. The diuretic dose may be adjusted and individualized as needed.
What happens
Reduced diuretic efficacy
Interaction Deep Dive
Concomitant use of codeine with diuretics may reduce the efficacy of diuretics by inducing the release of anti-diuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed1.
Why it happens (mechanism)
Increased opioid-mediated release of antidiuretic hormone
How to manage this interaction
Keep taking both medications as prescribed unless your care team tells you otherwise. This concern is theoretical, and it can be managed.
- Your team may monitor you more closely for signs the water pill is working less well, such as less urination, more swelling, or higher blood pressure.
- If needed, your diuretic dose may be adjusted and individualized by your care team.
- Tell your pharmacist or prescriber if you notice new swelling, weight gain, or blood pressure changes while using the codeine product.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Clopamide together?
Codeine may slightly weaken how well your water pill (Clopamide) works by causing fluid retention, but this is a theoretical concern your care team can manage with monitoring and dose adjustments if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Clopamide 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 Acetaminophen And Codeine and Clopamide interaction managed?
Keep taking both medications as prescribed unless your care team tells you otherwise. This concern is theoretical, and it can be managed. Your team may monitor you more closely for signs the water pill is working less well, such as less urination, more swelling, or higher blood pressure. If needed, your diuretic dose may be adjusted and individualized by your care team. Tell your pharmacist or pre… 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 Clopamide 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)
- 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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