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Drug interactions

Morphine + Phenobarbital

Severity: Major

Morphine and Phenobarbital: 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

Phenobarbital and morphine together cause additive sedation and respiratory depression. Phenobarbital may also induce hepatic glucuronidation and could modestly lower morphine exposure, but the CNS depressant effect is the main concern.

What this interaction means in plain words

Morphine and Phenobarbital 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.

Evidence level: High

Why it happens

Additive CNS depression via opioid receptor and GABA-A mediated effects.

What to do

Use the lowest effective doses and monitor for excessive sedation and respiratory depression, especially when starting or increasing either drug. Counsel patients to avoid alcohol and driving.

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?

Bring a full list of your medicines, including over-the-counter products, supplements and herbal remedies, to every pharmacy visit.

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References

Frequently asked questions

Can I take Morphine with Phenobarbital?

MediHelp rates the interaction as major. Morphine and Phenobarbital 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. Phenobarbital and morphine together cause additive sedation and respiratory depression. Phenobarbital may also induce hepatic glucuronidation and could modestly lower morphine exposure, but the CNS depressant effect is the main concern.

How serious is the interaction between Morphine and Phenobarbital?

MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use the lowest effective doses and monitor for excessive sedation and respiratory depression, especially when starting or increasing either drug. Counsel patients to avoid alcohol and driving.

What other medicines interact with Morphine?

MediHelp also lists interactions of Morphine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Morphine page.

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