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Drug interactions

Clomipramine + Nefazodone

Severity: Major

Clomipramine and Nefazodone: 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

Nefazodone inhibits CYP3A4 and may raise clomipramine levels, and both drugs enhance serotonergic activity. This increases the risk of tricyclic toxicity and serotonin syndrome.

What this interaction means in plain words

Clomipramine and Nefazodone 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: Moderate

Why it happens

CYP3A4 inhibition by nefazodone raises clomipramine exposure, combined with additive serotonin reuptake inhibition.

What to do

Avoid the combination if possible. If used, lower the clomipramine dose, monitor ECG and clinical signs of serotonin toxicity and tricyclic overdose.

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 Clomipramine with Nefazodone?

MediHelp rates the interaction as major. Clomipramine and Nefazodone 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. Nefazodone inhibits CYP3A4 and may raise clomipramine levels, and both drugs enhance serotonergic activity. This increases the risk of tricyclic toxicity and serotonin syndrome.

How serious is the interaction between Clomipramine and Nefazodone?

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 the combination if possible. If used, lower the clomipramine dose, monitor ECG and clinical signs of serotonin toxicity and tricyclic overdose.

What other medicines interact with Clomipramine?

MediHelp also lists interactions of Clomipramine with, for example, Arsenic trioxide, Dofetilide, Droperidol. The full list is on the Clomipramine page.

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