Lamotrigine and Acetaminophen: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 10, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lamotrigine
Acetaminophen
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
Decreased lamotrigine effectiveness
Interaction Deep Dive
In a randomized study, the effect of acetaminophen on the pharmacokinetics of lamotrigine was evaluated. When given concurrently, the half-life and area under the plasma concentration-time curve of lamotrigine decreased by 15% and 20% respectively. Renal clearance for lamotrigine increased by 7%1.
Why it happens (mechanism)
Increased renal clearance
Literature reports
1 report — tap to read
a) Acetaminophen enhances the urinary elimination of lamotrigine after single doses of the anticonvulsant. In healthy volunteers, administration of a single 300 mg dose of lamotrigine followed by acetaminophen 900 mg 3 times a day resulted in a decrease in AUC and serum half-life of 20% and 15%, respectively, compared to administration of lamotrigine with placebo. No differences in peak plasma concentration or time to peak were observed. The percentage of lamotrigine recovered in the urine was also higher when administered with acetaminophen. It was suggested that acetaminophen may enhance removal of lamotrigine from the circulation 1.
Common questions
Can I take Lamotrigine and Acetaminophen together?
Decreased lamotrigine effectiveness Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lamotrigine and Acetaminophen interaction?
It is rated minor. Usually limited clinical impact.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
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 Lamotrigine or Acetaminophen 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)
- Depot M, Powell JR, & Messenheimer JA: Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine. Clin Pharmacol Ther 1990; 48:346-355. PubMed
Keep reading about Lamotrigine
Keep reading about Acetaminophen
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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