Acetaminophen And Codeine and Hydroflumethiazide: 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
Hydroflumethiazide
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're taking a pain medicine that contains codeine (along with acetaminophen) and a water pill called hydroflumethiazide. Water pills help your body get rid of extra fluid and can help lower blood pressure. The concern here is that codeine may cause your body to hold onto more water, which could make your water pill work a little less well.
It's worth knowing this idea is theoretical, meaning it's based on how the drugs are expected to behave rather than strong proof. Still, it's a good thing to mention to your care team. They can keep an eye on your blood pressure and swelling and adjust things if needed, so this is very manageable.
Effect: Codeine may reduce the diuretic efficacy of hydroflumethiazide (a thiazide-type diuretic).
Mechanism: Opioid-mediated increase in antidiuretic hormone (ADH) release, promoting water retention and blunting the natriuretic/diuretic and antihypertensive response. This is a PD interaction, not a CYP-based one; codeine's prodrug status (CYP2D6 to morphine) is not the driver here.
Direction/magnitude: Reduced diuretic effect; magnitude unquantified.
Evidence/onset: Theoretical; onset unspecified.
- Monitor urine output, edema, weight, and blood pressure.
- Diuretic dose may be adjusted and individualized if diminished response is observed.
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 exactly as prescribed unless your care team tells you otherwise.
- Watch for reduced water-pill effect: more swelling in the legs or feet, quick weight gain, or blood pressure creeping up.
- Monitoring: your team may check your blood pressure and weight more closely.
- Dosing: if your diuretic seems less effective, the dose may need to be adjusted and individualized by your care team.
Let your pharmacist or doctor know you're on both, and report any new swelling or blood pressure changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Hydroflumethiazide together?
Codeine may make your water pill (hydroflumethiazide) work a bit less well by causing fluid retention. It's a theoretical concern, so keep taking both and let your care team monitor your blood pressure and swelling. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Hydroflumethiazide 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 Hydroflumethiazide interaction managed?
Keep taking both medications exactly as prescribed unless your care team tells you otherwise. Watch for reduced water-pill effect: more swelling in the legs or feet, quick weight gain, or blood pressure creeping up. Monitoring: your team may check your blood pressure and weight more closely. Dosing: if your diuretic seems less effective, the dose may need to be adjusted and individualized by your… 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 Hydroflumethiazide 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
Keep reading about Acetaminophen And Codeine
Keep reading about Hydroflumethiazide
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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