Drug interactions
Fluoxetine + Milnacipran
Severity: Major
Fluoxetine and Milnacipran: 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
Both drugs increase synaptic serotonin, so combining them raises the risk of serotonin syndrome. Milnacipran also raises norepinephrine, which may add to blood pressure and heart rate increases.
What this interaction means in plain words
Fluoxetine and Milnacipran 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.
Fluoxetine belongs to Central Nervous System; Milnacipran belongs to Central Nervous System.
Why it happens
Additive inhibition of serotonin reuptake producing excess serotonergic activity.
What to do
Avoid concurrent use where possible; if both must be given, use low doses and monitor for clonus, agitation, hyperthermia and autonomic instability. Stop both and give supportive care if serotonin syndrome develops.
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 Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Other interactions of Milnacipran
- Isocarboxazid + Milnacipran Contraindicated
- Methylene blue + Milnacipran Contraindicated
- Milnacipran + Phenelzine Contraindicated
- Milnacipran + Procarbazine Contraindicated
- Milnacipran + Rasagiline Contraindicated
- Milnacipran + Safinamide Contraindicated
Frequently asked questions
Can I take Fluoxetine with Milnacipran?
MediHelp rates the interaction as major. Fluoxetine and Milnacipran 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. Both drugs increase synaptic serotonin, so combining them raises the risk of serotonin syndrome. Milnacipran also raises norepinephrine, which may add to blood pressure and heart rate increases.
How serious is the interaction between Fluoxetine and Milnacipran?
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 where possible; if both must be given, use low doses and monitor for clonus, agitation, hyperthermia and autonomic instability. Stop both and give supportive care if serotonin syndrome develops.
What other medicines interact with Fluoxetine?
MediHelp also lists interactions of Fluoxetine with, for example, Isocarboxazid, Mavacamten, Methylene blue. The full list is on the Fluoxetine page.
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