Promethazine and codeine and Topiramate interaction
Promethazine and codeine and Topiramate: 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…
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.
Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor [ see Warnings and Precautions (5.9) , Drug Interactions (7.1 , 7.2 , 7.3 ) ].
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) ].
From the Topiramate label · effective 2026-05-15
Caution should be used when topiramate extended-release capsules are prescribed with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, other carbonic anhydrase inhibitors and drugs with anticholinergic activity.
Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, topiramate extended-release capsules should be used with extreme caution if used in combination with alcohol and other CNS depressants.
CNS Depressants Concomitant administration of topiramate and alcohol or other CNS depressant drugs has not been evaluated in clinical studies.
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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.