Ondansetron and Tramadol interaction

Ondansetron and Tramadol: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Ondansetron label · effective 2026-04-16

Major

Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Ondansetron Injection and other serotonergic drugs.

Warnings and precautionsby drug classView label on DailyMed
Major

Patients should be informed of the increased risk of serotonin syndrome, especially if Ondansetron Injection is used concomitantly with other serotonergic drugs [see Drug Interactions (7.5 ), Overdosage (10) ] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

Tramadol Although there are no data on pharmacokinetic drug interactions between ondansetron and tramadol, data from two small trials indicate that concomitant use of ondansetron may result in reduced analgesic activity of tramadol.

Drug interactionsnames TramadolView label on DailyMed
Moderate

Patients on concomitant ondansetron self-administered tramadol more frequently in these trials, leading to an increased cumulative dose in patient-controlled administration of tramadol.

Drug interactionsnames TramadolView label on DailyMed
Minor

Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue).

Warnings and precautionsnames TramadolView label on DailyMed

From the Tramadol (Tramadol Hydrochloride Extended-Release) label · effective 2026-01-23

Moderate

…and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see Warnings…

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.