Promethazine and codeine and Tizanidine interaction
Promethazine and codeine 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 Promethazine and codeine (Promethazine Hydrochloride and Codeine Phosphate) label · effective 2025-12-18
…PROMETHAZINE AND RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Promethazine HCl and Codeine Phosphate Oral Solution exposes patients and other users to the risks…
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.
Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients taking benzodiazepines, other CNS depressants, or alcohol [ see Warnings and Precautions (5.10) , Drug Interactions (7.4) ].
( 5.9 , 7.1 , 7.2 , 7.3 ) 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.
Avoid concurrent use of Promethazine HCl and Codeine Phosphate Oral Solution with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur [ see Warnings and Precautions (5.10) ].
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.
To minimize the risk of these reactions, particularly in patients who have been receiving high doses of Zanaflex (20 to 28 mg daily) for long periods of time (9 weeks or more) or who may be on concomitant treatment with narcotics, the Zanaflex dosage should be decreased slowly [see Dosage and Administration ( 2.5 )] .
Alcohol and Other CNS Depressants Alcohol increases the exposure of tizanidine after administration of Zanaflex.
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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.