Sertraline and Benzhydrocodone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Benzhydrocodone
No brand names on recordSertraline
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 benzhydrocodone (an opioid pain medicine that turns into hydrocodone in your body) along with sertraline, an antidepressant. Both can raise a brain chemical called serotonin. When two medicines do this together, there's a small chance of a reaction called serotonin syndrome.
Signs to watch for include feeling agitated or confused, a fast heartbeat, shivering, sweating, muscle twitching or stiffness, or a fever. This is uncommon, and many people take these two together safely. The good news is your care team can manage this by watching you closely, especially when you first start or change a dose. If you notice those symptoms, reach out to your doctor or pharmacist right away.
Effect: Additive serotonergic activity increasing the theoretical risk of serotonin syndrome. Benzhydrocodone is a prodrug hydrolyzed to hydrocodone; opioids like hydrocodone have weak serotonergic properties that may add to sertraline's SSRI-mediated serotonin reuptake inhibition.
- Direction: Additive PD interaction (not a metabolic/PK inhibition effect).
- Severity/Evidence: Major severity, but evidence is theoretical.
- Onset: Unspecified; highest vigilance at initiation and dose changes.
- Management: Co-use is acceptable when needed. Monitor for autonomic instability, neuromuscular abnormalities (clonus, rigidity), altered mental status, and hyperthermia. Discontinue the opioid if serotonin syndrome is suspected.
What happens
An increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has been reported when opioids like HYDROcodone are taken together with serotonergic agents. When such combined therapy is required, monitor the patient closely, especially at the start of treatment and when doses are being changed. Should serotonin syndrome be suspected, stop HYDROcodone1234.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
This combination can be used together when your care team decides it's needed. Here's how they typically handle it:
- Closer monitoring, especially when you start either drug or change a dose.
- The dose may be adjusted and individualized by your care team.
- If serotonin syndrome is suspected, your prescriber may stop the opioid.
What you can do: Keep taking both medicines exactly as prescribed unless told otherwise. Tell your pharmacist or doctor promptly if you feel agitated, confused, shaky, sweaty, feverish, or notice a racing heart or muscle twitching. Ask before adding any other serotonergic medicines.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Sertraline and Benzhydrocodone together?
Taking benzhydrocodone with sertraline slightly raises the risk of serotonin syndrome, so watch for agitation, shivering, sweating, fast heartbeat, or muscle twitching, especially early on, and report symptoms to your care team right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Benzhydrocodone 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 Sertraline and Benzhydrocodone interaction managed?
This combination can be used together when your care team decides it's needed. Here's how they typically handle it: Closer monitoring, especially when you start either drug or change a dose. The dose may be adjusted and individualized by your care team. If serotonin syndrome is suspected, your prescriber may stop the opioid. What you can do: Keep taking both medicines exactly as prescribed unless… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Sertraline or Benzhydrocodone 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 (4)
- Product Information: NORCO 5/325 oral tablets, hydrocodone bitartrate acetaminophen oral tablets. Allergan USA, Inc. (per DailyMed), Irvine, CA, 2016.
- Product Information: VANTRELA(TM) ER oral extended-release tablets, hydrocodone bitartrate oral extended-release tablets. Teva Pharmaceuticals USA, Inc (per manufacturer), North Wales, PA, 2017. DailyMed
- Product Information: HYSINGLA(R) ER oral extended-release tablets, hydrocodone bitartrate oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
- Product Information: APADAZ(R) oral tablets, benzhydrocodone acetaminophen oral tablets. Zevra Therapeutics, Inc. (per FDA), Celebration, FL, 2023. DailyMed
Keep reading about Benzhydrocodone
Keep reading about Sertraline
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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