Drug interactions
Codeine + Hydrocodone
Severity: Major
Codeine and Hydrocodone: major interaction.
Last updated Sources: US FDA label
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
Two opioid agonists taken together produce additive sedation and respiratory depression that can lead to coma or death. Duplicate opioid therapy rarely offers an advantage over optimising one agent.
What this interaction means in plain words
Codeine and Hydrocodone 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.
Codeine belongs to Musculoskeletal; Hydrocodone belongs to Musculoskeletal.
Why it happens
Additive mu-opioid receptor mediated CNS and respiratory depression.
What to do
Avoid concurrent use and consolidate to a single opioid. If unavoidable, use minimal doses and duration, monitor respiration and sedation, and ensure naloxone is available.
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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References
Other interactions of Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine Major
Other interactions of Hydrocodone
- Alvimopan + Hydrocodone Contraindicated
- Bupropion-naltrexone + Hydrocodone Contraindicated
- Hydrocodone + Isocarboxazid Contraindicated
- Hydrocodone + Olanzapine / samidorphan Contraindicated
- Hydrocodone + Phenelzine Contraindicated
- Alfentanil + Hydrocodone Major
Frequently asked questions
Can I take Codeine with Hydrocodone?
MediHelp rates the interaction as major. Codeine and Hydrocodone 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. Two opioid agonists taken together produce additive sedation and respiratory depression that can lead to coma or death. Duplicate opioid therapy rarely offers an advantage over optimising one agent.
How serious is the interaction between Codeine and Hydrocodone?
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 and consolidate to a single opioid. If unavoidable, use minimal doses and duration, monitor respiration and sedation, and ensure naloxone is available.
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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