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What the FDA labels say about taking them together

Doxepin and sertraline

Doxepin's FDA label (Prudoxin) of June 29, 2017 names sertraline in its drug interactions section; sertraline's label does not name doxepin itself but warns about its class (Tricyclic antidepressants). The doxepin label: “While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.”

Check it at the source: the doxepin FDA label on DailyMed (effective December 30, 2025, Leading Pharma, LLC); the sertraline FDA label on DailyMed (effective August 8, 2023, Viatris Specialty LLC).

What does the doxepin label say about sertraline?

Prudoxin label (Mylan Pharmaceuticals Inc., June 29, 2017), drug interactions

While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.

Source: FDA drug label (Prudoxin, NDA020126), Mylan Pharmaceuticals Inc., effective June 29, 2017 (SPL set ca53346b-8ab3-4722-98f6-cf272706d3fa), via openFDA

Source: FDA drug label (DOXEPIN HYDROCHLORIDE), Leading Pharma, LLC, effective December 30, 2025 (SPL set e6a4cb10-1928-4abe-8797-404c9ddc37dd), via openFDA; the full label on DailyMed

What does the sertraline label say about doxepin?

Sertraline's label does not name doxepin itself; it warns about its class (Tricyclic antidepressants):

Sertraline label, drug interactions

If serotonin syndrome occurs, consider discontinuation of ZOLOFT and/or concomitant serotonergic drugs [See Warnings and Precautions (5.2) ]. Other SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St. John’s Wort.

Sertraline label, warnings and precautions

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. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [See Contraindications (4), Drug Interactions (7.1) ].

Source: FDA drug label (Zoloft), Viatris Specialty LLC, effective August 8, 2023 (SPL set fda754f6-d0f3-4dce-a17a-927d64f912f7), via openFDA; the full label on DailyMed

These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.

Both medicines on the record

49Doxepin generic labelers
47Sertraline generic labelers
DoxepinSertraline
Labeled forDepression, Anxiety, Eczema (atopic dermatitis), InsomniaDepression, Anxiety
Boxed warningYesYes
Pharmacy cost (NADAC)$0.0779 per capsule 10 mg capsule$0.0507 per tablet 100 mg tablet
Shortage nowNo current entryNo current entry

Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)

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