Tramadol and Nafcillin Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tramadol
Nafcillin Injection
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 traMADol exposure, reduced efficacy of traMADol and an increased risk of seizure
Interaction Deep Dive
Concomitant use of traMADol with seizure threshold lowering CYP3A4 inducer may result in reduced traMADol exposure, resulting in reduced efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to traMADol and may also increase risk of seizure. Risk of seizure may also increase in patients with epilepsy, those with a history of seizures, or in patients with a recognized risk for seizure (such as head trauma, metabolic disorders, alcohol and drug withdrawal, CNS infections). After stopping a CYP3A4 inducer, as the effects of the inducer decline, the traMADol exposure will increase, which could increase or prolong both the therapeutic effects and adverse reactions, and may cause seizures, serotonin syndrome, and/or potentially fatal respiratory depression. If concomitant use is needed, closely monitor patients for decreased efficacy or signs of opioid withdrawal syndrome, and consider increasing the dose of traMADol as necessary. If a CYP3A4 inducer is being discontinued, consider traMADol dose reduction and closely monitor patients for signs of seizures, serotonin syndrome, respiratory depression or sedation1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of traMADol; additive lowering of seizure threshold
Common questions
Can I take Tramadol and Nafcillin Injection together?
Reduced traMADol exposure, reduced efficacy of traMADol and an increased risk of seizure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tramadol and Nafcillin Injection 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 Tramadol or Nafcillin Injection 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 (1)
- Product Information: Tramadol hydrochloride oral tablets, tramadol hydrochloride oral tablets. Strides Pharma, Inc (per DailyMed), East Brunswick, NJ, 2025. DailyMed
Keep reading about Tramadol
Keep reading about Nafcillin Injection
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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:
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