Drug interactions
Codeine + Fentanyl
Severity: Major
Codeine and Fentanyl: 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 opioids together add to sedation, respiratory depression and hypotension. Codeine is a prodrug, and combined use brings no safety advantage over a single opioid.
What this interaction means in plain words
Codeine and Fentanyl 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; Fentanyl belongs to Musculoskeletal.
Why it happens
Additive mu-opioid receptor agonism with CNS and respiratory depression.
What to do
Avoid routine duplication of opioids; if both are needed, reduce doses and monitor sedation and respiratory rate.
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 Fentanyl
- Alvimopan + Fentanyl Contraindicated
- Fentanyl + Isocarboxazid Contraindicated
- Fentanyl + Olanzapine / samidorphan Contraindicated
- Fentanyl + Phenelzine Contraindicated
- Fentanyl + Tranylcypromine Contraindicated
- Alfentanil + Fentanyl Major
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 Codeine with Fentanyl?
MediHelp rates the interaction as major. Codeine and Fentanyl 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 opioids together add to sedation, respiratory depression and hypotension. Codeine is a prodrug, and combined use brings no safety advantage over a single opioid.
How serious is the interaction between Codeine and Fentanyl?
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 routine duplication of opioids; if both are needed, reduce doses and monitor sedation and respiratory rate.
What other medicines interact with Fentanyl?
MediHelp also lists interactions of Fentanyl with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Fentanyl page.
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