Drug Interaction Report

Acetaminophen Rectal and Piperaquine: Interaction Details

Name: Acetaminophen Rectal and Piperaquine Interaction
Creator: Dr. Brian Staiger, PharmD, BCPS

A pharmacist-reviewed analysis of the Acetaminophen Rectal and Piperaquine interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Piperaquine

No brand names on record

Acetaminophen Rectal

Acephen Acephen Rectal Suppository® Feverall Feverall Rectal Suppository® Neopap Supprettes Rectal Suppository® Tylenol Rectal Suppository®

Medically reviewed by

Dr. Brian Staiger, PharmD, BCPS

Updated Jul 10, 2026

Editorial policy · Data sources

Interaction severity

Moderate

Can be significant — usually manageable with monitoring.

Minor

Moderate

Major

Contraindicated

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 28 documented Acetaminophen Rectal interactions, 13 are rated moderate — including this one.

Onset

unspecified

Evidence

theoretical

Severity

Moderate

What happens

Reduced exposure of CYP2E1 substrates

Interaction Deep Dive

Concurrent administration of piperaquine (a CYP2E1 inducer) and a CYP2E1 substrate may decrease the exposure and efficacy of the CYP2E1 substrate¹.

Why it happens (mechanism)

Induction of CYP2E1-mediated metabolism by piperaquine

Common questions

Can I take Acetaminophen Rectal and Piperaquine together?

Reduced exposure of CYP2E1 substrates Always confirm with your pharmacist or prescriber before making any change.

How serious is the Acetaminophen Rectal and Piperaquine 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 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 Rectal or Piperaquine 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)

Product Information: Eurartesim oral film-coated tablets, piperaquine tetraphosphate dihydroartemisinin oral film-coated tablets. Sigma-Tau Industrie Farmaceutiche Riunite S.p.A (per EMA), Rome, Italy, 2012.

Was this write-up helpful?

Piperaquine

Keep reading about Piperaquine

All Piperaquine interactions (91)

Also serious with: Lenvatinib Histrelin Implant Granisetron Transdermal Patch Moxifloxacin

Acetaminophen Rectal

Keep reading about Acetaminophen Rectal

All Acetaminophen Rectal interactions (28) Acetaminophen Rectal drug information

Also serious with: Articaine Carbamazepine Exenatide Flucloxacillin

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist

A message from HelloPharmacist

About our interaction database: depth, not breadth

HelloPharmacist doesn't license one of the big commercial interaction databases, so what you'll find here is not a complete list of every known drug interaction. Instead, each entry is researched, analyzed, and written up individually — documented from the published literature, reviewed by a pharmacist, and cited so you can check every source yourself.

If a combination isn't listed here, it means we haven't documented it yet — never that it's safe. For screening a full medication list, we recommend pairing this site with a comprehensive tool like the Drugs.com Interaction Checker and, most importantly, a review by your own pharmacist. For a deep, plain-English, fully sourced explanation of a specific documented interaction — that's exactly what we built this for.

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.