Penbutolol and Lidocaine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 9, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lidocaine
Penbutolol
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.
What happens
An increase in the volume of distribution and a prolongation of the elimination half-life of lidocaine
Interaction Deep Dive
One study has shown that penbutolol increases the volume of distribution and the elimination half-life of lidocaine during a single intravenous administration1. Possible mechanisms for the alteration in the pharmacokinetic profile of lidocaine include changes in the pattern of peripheral blood flow induced by penbutolol, causing a change in the characteristics of lidocaine tissue uptake and distribution.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) A study was conducted on the pharmacokinetics of lidocaine in seven healthy volunteers when administered as a single intravenous dose alone and when preceded by three days of therapy with penbutolol 60 mg daily. Penbutolol coadministration resulted in an increased lidocaine volume of distribution, from 3.36 L/kg to 4.85 L/kg (p less than 0.005). The increase in volume of distribution caused a prolongation of the half-life of lidocaine from 2.0 hours to 2.5 hours (p less than 0.025). However, the total metabolic clearance of lidocaine was not significantly altered. The authors concluded that while a higher loading dose of lidocaine may be required in a patient receiving penbutolol, the steady-state concentration of lidocaine during a continuous infusion should remain unchanged by penbutolol coadministration 1.
Common questions
Can I take Penbutolol and Lidocaine together?
An increase in the volume of distribution and a prolongation of the elimination half-life of lidocaine Always confirm with your pharmacist or prescriber before making any change.
How serious is the Penbutolol and Lidocaine interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Penbutolol or Lidocaine 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)
- Ochs HR, Skanderra D, Abernethy DR, et al: Effect of penbutolol on lidocaine kinetics. Arzneimittelforschung 1983; 33:1680-1681.
Keep reading about Lidocaine
Keep reading about Penbutolol
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