Frovatriptan and Acetaminophen And Codeine: 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
Frovatriptan
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 given acetaminophen with codeine (a pain medicine) and frovatriptan (Frova, a migraine medicine). Both can gently raise levels of a brain chemical called serotonin. When two serotonin-boosting drugs are combined, there's a small chance they can push serotonin too high, a reaction called serotonin syndrome.
Signs to watch for include feeling restless or agitated, a fast heartbeat, sweating, shivering, muscle twitching, or confusion. This concern is mostly based on theory, not strong proof, so many people take both without trouble. Keep taking both as prescribed, and let your care team know about all your medicines so they can watch you closely, especially when starting or changing a dose.
Effect: Additive serotonergic activity, theoretically increasing serotonin syndrome risk. Codeine (and its metabolites) has weak serotonergic properties; frovatriptan is a 5-HT1B/1D agonist. Combined use can additively elevate serotonergic tone.
- Direction: Additive PD effect (not a metabolic/PK interaction); increased serotonergic burden.
- Severity/Evidence: Major severity, but theoretical substantiation.
- Onset: Unspecified; highest vigilance at initiation and dose changes.
- Management: If co-use is needed, monitor for agitation, hyperthermia, tachycardia, diaphoresis, clonus, hyperreflexia, altered mentation. Discontinue codeine if serotonin syndrome is suspected and treat supportively.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Concomitant use of opioids, such as codeine, with serotonergic drugs has resulted in serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments. Discontinue codeine if serotonin syndrome is suspected123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
The good news: this is a theoretical concern, and your care team can manage it by watching you carefully.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Be extra alert when starting either drug or changing a dose, since that's when risk is highest.
- Know the warning signs: agitation, fast heartbeat, sweating, shivering, muscle twitching or stiffness, fever, or confusion.
- Seek prompt care if these appear, and tell your pharmacist and prescriber you take both medicines so they can monitor you and adjust your plan if needed.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Frovatriptan and Acetaminophen And Codeine together?
Combining codeine with frovatriptan carries a theoretical risk of serotonin syndrome from additive serotonergic effects. Keep taking both as prescribed, watch for agitation, sweating, fast heartbeat, shivering, or muscle twitching, and get medical help if these occur. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Frovatriptan 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 Frovatriptan and Acetaminophen And Codeine interaction managed?
The good news: this is a theoretical concern, and your care team can manage it by watching you carefully. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Be extra alert when starting either drug or changing a dose, since that's when risk is highest. Know the warning signs: agitation, fast heartbeat, sweating, shivering, muscle twitching or stiffness, fever, or co… 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 Frovatriptan 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 (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 Frovatriptan
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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