Drug interactions
Alprazolam + Phenobarbital
Severity: Major
Alprazolam and Phenobarbital: major interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Phenobarbital is a potent enzyme inducer that can lower alprazolam concentrations and reduce its effect. Both agents also depress the CNS, so sedation and respiratory depression may be additive.
What this interaction means in plain words
Alprazolam and Phenobarbital can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Phenobarbital induces CYP3A4, increasing alprazolam clearance, and both drugs enhance GABAergic inhibition.
What to do
Monitor for loss of alprazolam efficacy and for excess sedation or respiratory depression, and adjust the alprazolam dose accordingly. Re-evaluate dosing if phenobarbital is started or stopped.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to see why Alprazolam and Phenobarbital interact, what to do about it, and the sources.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 14 days on the web. No card needed.
Other interactions of Alprazolam
- Alprazolam + Calcium / magnesium / potassium / sodium oxybates Contraindicated
- Alprazolam + Itraconazole Contraindicated
- Alprazolam + Ketoconazole Contraindicated
- Alprazolam + Levoketoconazole Contraindicated
- Alprazolam + Sodium oxybate Contraindicated
- Alfentanil + Alprazolam Major
Frequently asked questions
Can I take Alprazolam with Phenobarbital?
MediHelp rates the interaction as major. Alprazolam and Phenobarbital can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Phenobarbital is a potent enzyme inducer that can lower alprazolam concentrations and reduce its effect. Both agents also depress the CNS, so sedation and respiratory depression may be additive.
How serious is the interaction between Alprazolam and Phenobarbital?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for loss of alprazolam efficacy and for excess sedation or respiratory depression, and adjust the alprazolam dose accordingly. Re-evaluate dosing if phenobarbital is started or stopped.
What other medicines interact with Alprazolam?
MediHelp also lists interactions of Alprazolam with, for example, Calcium / magnesium / potassium / sodium oxybates, Itraconazole, Ketoconazole. The full list is on the Alprazolam page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
