Ketamine and Tizanidine interaction
Ketamine and Tizanidine: 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 Ketamine (Ketalar) label · effective 2026-03-27
Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death.
Benzodiazepines, Opioid Analgesics, or Other CNS Depressants Concomitant use of ketamine with opioid analgesics, benzodiazepines, or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Drug Interactions ( 7.3 )] .
Closely monitor neurological status and respiratory parameters, including respiratory rate and pulse oximetry, when KETALR and opioid analgesics, benzodiazepines, or other CNS depressants are co-administered.
Benzodiazepines, Opioid Analgesics, Or Other CNS Depressants Concomitant use of ketamine with opioid analgesics, benzodiazepines, or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions ( 5.9 )] .
Muscle relaxants may be required.
From the Tizanidine (Zanaflex) label · effective 2026-01-02
Sedation: Zanaflex may interfere with everyday activities; sedative effects of Zanaflex, alcohol, and other central nervous system (CNS) depressants are additive ( 5.3 , 7.4 )
The CNS depressant effects of Zanaflex with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive [see Drug Interactions ( 7.4 )] .
Monitor patients who take Zanaflex with another CNS depressant for symptoms of excess sedation.
Alcohol and Other CNS Depressants Alcohol increases the exposure of tizanidine after administration of Zanaflex.
Concomitant use of Zanaflex with CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may cause additive CNS depressant effects, including sedation.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
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.