Butalbital, acetaminophen, caffeine, and codeine and Ketamine interaction

Butalbital, acetaminophen, caffeine, and codeine and Ketamine: 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 Ketamine (Ketalar) label · effective 2026-03-27

Major

Theophylline or Aminophylline : Do not co-administer with KETALAR as concomitant use may lower the seizure threshold ( 7.1 ).

Drug interactionsby drug classView label on DailyMed
Major

Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death.

Drug interactionsby drug classView label on DailyMed
Moderate

Consider using an alternative to KETALAR in patients receiving theophylline or aminophylline.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Sympathomimetics and Vasopressin : Sympathomimetics and vasopressin may enhance the sympathomimetic effects of ketamine [see Drug Interactions ( 7.2 )] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

Closely monitor vital signs when KETALAR and sympathomimetics or vasopressin are co-administered and consider dose adjustment individualized to the patient’s clinical situation.

Warnings and precautionsby drug classView label on DailyMed

From the Butalbital, acetaminophen, caffeine, and codeine (Butalbital, Acetaminophen, Caffeine and Codeine Phosphate) label · effective 2026-01-02

Major

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.

Boxed warningby drug classView label on DailyMed
Major

Reserve concomitant prescribing of Butalbital, Acetaminophen, Caffeine, and Codeine Phosphate Capsules 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 )] .

Boxed warningby drug classView label on DailyMed
Major

• Concomitant use of opioids or a barbiturate with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions ( 7 )].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.

Warnings and precautionsby 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.