Nefazodone and Sertraline interaction

Nefazodone and Sertraline: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Nefazodone (Nefazodone Hydrochloride) label · effective 2025-07-31

Major

Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.

Boxed warningby drug classView label on DailyMed
Major

Nefazodone hydrochloride tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone hydrochloride, its inactive ingredients, or other phenylpiperazine antidepressants.

Contraindicationsby drug classView label on DailyMed
Minor

Hyponatremia : Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including nefazodone.

Warningsby drug classView label on DailyMed
Minor

For a selective serotonin reuptake inhibitor (SSRI), these reactions have included hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.

Warningsby drug classView label on DailyMed

From the Sertraline (sertraline hydrochloride) label · effective 2025-08-06

Major

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of sertraline hydrochloride capsules with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

Warnings and precautionsby drug classView label on DailyMed
Moderate

The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St.

Warnings and precautionsby drug classView label on DailyMed
Minor

Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with sertraline hydrochloride capsules or another antidepressant may precipitate a mixed/manic episode.

Warnings and precautionsby drug classView label on DailyMed
Minor

Other Serotonergic Drugs Clinical Impact: Concomitant use of sertraline hydrochloride capsules with other serotonergic drugs (including other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St.

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.