Codeine and Pregabalin interaction

Codeine and Pregabalin: 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 Codeine (Codeine sulfate) label · effective 2025-12-22

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 Codeine Sulfate 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 )] .

Boxed warningby drug classView label on DailyMed
Major

• 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

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Codeine Sulfate Tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general…

Warnings and precautionsby drug classView label on DailyMed
Major

Advise both patients and caregivers about the risks of respiratory depression and sedation when Codeine Sulfate Tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).

Warnings and precautionsby drug classView label on DailyMed

From the Pregabalin (Lyrica CR) label · effective 2026-03-12

Major

• Respiratory Depression : May occur with LYRICA when used with concomitant CNS depressants or in the setting of underlying respiratory impairment.

Warnings and precautionsby drug classView label on DailyMed
Major

Respiratory Depression There is evidence from case reports, human studies, and animal studies associating pregabalin with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment.

Warnings and precautionsby drug classView label on DailyMed
Major

The management of respiratory depression may include close observation, supportive measures, and reduction or withdrawal of CNS depressants (including LYRICA CR).

Warnings and precautionsby drug classView label on DailyMed
Major

There is more limited evidence from case reports, animal studies, and human studies associating pregabalin with serious respiratory depression, without co-administered CNS depressants or without underlying respiratory impairment.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When the decision is made to co-prescribe LYRICA CR with another CNS depressant, particularly an opioid, or to prescribe LYRICA CR to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating LYRICA CR at a low dose.

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.