Drug interactions
Benzhydrocodone / acetaminophen + Codeine
Severity: Major
Benzhydrocodone / acetaminophen and Codeine: major interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Benzhydrocodone is a prodrug of hydrocodone, so using it with codeine means two opioid agonists are given together. This duplicates opioid effects and increases the risk of profound sedation, respiratory depression, coma and death, and the acetaminophen adds a hepatotoxicity concern.
What this interaction means in plain words
Benzhydrocodone / acetaminophen and Codeine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Additive mu-opioid receptor agonism producing summed CNS and respiratory depression.
What to do
Avoid concurrent use of two opioids; choose a single opioid regimen. If overlap cannot be avoided, use the lowest doses for the shortest time and monitor closely for sedation and respiratory depression.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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Other interactions of Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine Major
Frequently asked questions
Can I take Benzhydrocodone / acetaminophen with Codeine?
MediHelp rates the interaction as major. Benzhydrocodone / acetaminophen and Codeine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Benzhydrocodone is a prodrug of hydrocodone, so using it with codeine means two opioid agonists are given together. This duplicates opioid effects and increases the risk of profound sedation, respiratory depression, coma and death, and the acetaminophen adds a hepatotoxicity concern.
How serious is the interaction between Benzhydrocodone / acetaminophen and Codeine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid concurrent use of two opioids; choose a single opioid regimen. If overlap cannot be avoided, use the lowest doses for the shortest time and monitor closely for sedation and respiratory depression.
What other medicines interact with Codeine?
MediHelp also lists interactions of Codeine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Codeine page.
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