Acetaminophen And Codeine and Lofepramine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Lofepramine
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.
Your pain medicine contains codeine, and lofepramine is an antidepressant. Both can raise levels of a brain chemical called serotonin. When two medicines do this together, there is a small chance of a reaction called serotonin syndrome. Signs can include feeling agitated or shaky, a fast heartbeat, sweating, muscle twitching, or a high fever.
This is mostly a theoretical concern, and many people take both without trouble. The most important time to watch is when you first start or when a dose changes. Please don't stop either medicine on your own. Your pharmacist or doctor can keep an eye on you and adjust things if needed.
Effect: Additive serotonergic activity from codeine (a weak serotonergic opioid) combined with lofepramine (a tricyclic antidepressant with serotonin reuptake inhibition) may increase the risk of serotonin syndrome.
- Mechanism: PD additive serotonergic effect.
- Direction: Increased serotonergic toxicity risk.
- Evidence: Theoretical; severity rated major.
- Onset: Unspecified; highest vigilance at initiation and dose titration.
- Management: Monitor for agitation, clonus, hyperreflexia, autonomic instability, hyperthermia. Discontinue codeine if serotonin syndrome is suspected; dose may be individualized by the care team.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has been reported when opioids like codeine are taken together with serotonergic agents. When such combined therapy is required, monitor the patient closely, especially when starting treatment and when doses are being changed. If serotonin syndrome is suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Both drugs can be used together when a prescriber decides it's appropriate, but your care team will watch you more closely, especially when starting either drug or changing a dose.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely and can adjust and individualize your doses if needed.
- Get prompt help if you notice agitation, confusion, a racing heart, sweating, shivering, muscle twitching or stiffness, or fever.
Ask your pharmacist or prescriber before adding any other medicine that affects serotonin.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Acetaminophen And Codeine and Lofepramine together?
Combining codeine with lofepramine carries a small, mostly theoretical risk of serotonin syndrome, so watch for agitation, rapid heartbeat, sweating, or muscle twitching, especially when starting or changing doses. Keep taking both as prescribed and contact your care team if these symptoms appear. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Lofepramine 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 Lofepramine interaction managed?
Both drugs can be used together when a prescriber decides it's appropriate, but your care team will watch you more closely, especially when starting either drug or changing a dose. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely and can adjust and individualize your doses if needed. Get prompt help if you notice agitation,… 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 Lofepramine 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 (3)
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. West-Ward Pharmaceuticals Corp (per DailyMed), Eatontown, NJ, 2016. DailyMed
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Lofepramine
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