Clobazam and Amitriptyline: 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
Amitriptyline
Clobazam
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 amitriptyline (a medication for mood or nerve pain) along with clobazam (a seizure medicine). The concern here is that clobazam may slow down how your body breaks down amitriptyline. When that happens, more amitriptyline can build up in your blood, which could lead to stronger side effects like drowsiness, dry mouth, constipation, dizziness, or a faster heartbeat.
I want to reassure you that this is based mostly on theory, not strong real-world reports. Your care team can manage this easily by watching how you feel, checking blood levels if needed, and fine-tuning your dose. Please keep taking both as prescribed and mention any new drowsiness or side effects to your pharmacist or doctor.
Effect: Increased amitriptyline exposure. Mechanism: Clobazam may inhibit CYP2D6-mediated metabolism of amitriptyline (a CYP2D6 substrate), reducing clearance and raising plasma concentrations. Neither agent's active effect is prodrug-dependent here, so the direction is straightforward augmentation of amitriptyline levels.
- Direction: Increased tricyclic exposure / anticholinergic, sedative, and cardiac (QT/conduction) effects.
- At-risk: CYP2D6 poor metabolizers.
- Evidence: Theoretical; onset unspecified.
- Management: Use caution, monitor clinically, obtain amitriptyline plasma levels, and reduce dose if indicated. If clobazam is discontinued, amitriptyline dose may need increasing.
What happens
Increased exposure of amitriptyline
Interaction Deep Dive
When amitriptyline, which is metabolized by CYP2D6, is taken together with an agent that inhibits CYP2D6, amitriptyline exposure can rise. Individuals who are poor metabolizers face a particularly elevated risk. Should combined use be necessary, exercise caution and keep the patient under close observation. It is also advisable to check plasma concentrations of amitriptyline and modify the dose as required. Discontinuation of the CYP2D6 inhibitor may necessitate raising the amitriptyline dose1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism of amitriptyline
How to manage this interaction
Good news is that your care team can manage this together with a few simple steps:
- Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for side effects like drowsiness, dry mouth, constipation, or a fast heartbeat.
- They may check your amitriptyline blood level and adjust and individualize the dose if needed.
- If your clobazam is ever stopped, your amitriptyline dose may need to be raised again.
Let your pharmacist or doctor know about any new or worsening symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Clobazam and Amitriptyline together?
Clobazam may raise amitriptyline levels, so watch for stronger side effects; your care team can manage this by monitoring you and adjusting the dose. Keep taking both as prescribed and report new symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clobazam and Amitriptyline 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 is the Clobazam and Amitriptyline interaction managed?
Good news is that your care team can manage this together with a few simple steps: Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for side effects like drowsiness, dry mouth, constipation, or a fast heartbeat. They may check your amitriptyline blood level and adjust and individualize the dose if needed. If 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Clobazam or Amitriptyline 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: amitriptyline HCl oral tablet, amitriptyline HCl oral tablet. RemedyRepack Inc. (per DailyMed), Indiana, PA, 2010. DailyMed
Keep reading about Amitriptyline
Keep reading about Clobazam
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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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