Tapentadol and Zonisamide interaction
Tapentadol and Zonisamide: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Tapentadol label · effective 2026-02-26
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of tapentadol tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [ see Warnings and Precautions (5.3) , Drug Interactions (7) ] .
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Profound sedation, respiratory depression, coma, and death may result from the concomitant use of tapentadol tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics,…
Advise both patients and caregivers about the risks of respiratory depression and sedation when tapentadol tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).
From the Zonisamide (ZONISADE) label · effective 2025-09-08
Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when ZONISADE is used with other drugs with sedative properties because of potential additive effects.
• ZONISADE should be used with caution if used in combination with alcohol or other CNS depressants ( 7.1 ).
CNS Depressants Concomitant use of ZONISADE with other CNS depressants, including alcohol, may increase the risk of CNS depression, as well as other cognitive and/or neuropsychiatric adverse events [see Warnings and Precautions ( 5.11 )] .
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Open in the checkerNot 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.