Primidone and Lefamulin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Primidone
Lefamulin
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
Reduced lefamulin exposure, reduced efficacy of lefamulin and an increased risk of QT interval prolongation
Interaction Deep Dive
Avoid concomitant use of lefamulin with PHENobarbital (strong/moderate CYP3A4 inducer or P-gp inducer) unless the benefit outweighs the risks, as it may reduce lefamulin exposure and may also reduce efficacy of lefamulin1. Also, avoid the concomitant use of PHENobarbital with other products with a known potential to prolong the QTc interval or products that may increase concentrations of PHENobarbital. PHENobarbital causes QTc interval prolongation. Concomitant use of PHENobarbital with other products that prolong the QTc interval like lefamulin may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation. If concomitant use of lefamulin and PHENobarbital is unavoidable, monitor patients for increased risk of QTc interval prolongation 2.
Why it happens (mechanism)
Induction of CYP3A-mediated metabolism of lefamulin; additive QT interval prolongation
Literature reports
1 report — tap to read
a) Oral rifAMPin (a strong CYP3A inducer and P-gp inducer) reduced the mean lefamulin AUC(0 to inf) and Cmax by 28% and 8%, respectively, when administered concomitantly with IV lefamulin. Additionally, oral rifAMPin reduced the mean lefamulin AUC(0 to inf) and Cmax by 72% and 57%, respectively, when administered concomitantly with oral lefamulin 1.
Common questions
Can I take Primidone and Lefamulin together?
Reduced lefamulin exposure, reduced efficacy of lefamulin and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Primidone and Lefamulin 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 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 Primidone or Lefamulin 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 (2)
- Product Information: XENLETA(R) oral tablets, intravenous injection, lefamulin oral tablets, intravenous injection. Nabriva Therapeutics US Inc (per FDA), King of Prussia, PA, 2021. DailyMed
- Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022. DailyMed
Keep reading about Primidone
Keep reading about Lefamulin
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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