What the FDA labels say about taking them together
Protriptyline and tramadol
Protriptyline's FDA label of July 25, 2023 names tramadol in its drug interactions section; tramadol's label does not name protriptyline itself but warns about its class (Tricyclic antidepressants). The protriptyline label: “Tricyclic antidepressants may enhance the seizure risk in patients taking ULTRAM (tramadol hydrochloride).”
Check it at the source: the protriptyline FDA label on DailyMed (effective July 25, 2023, Epic Pharma, LLC); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).
What does the protriptyline label say about tramadol?
Protriptyline label, drug interactionsTricyclic antidepressants may enhance the seizure risk in patients taking ULTRAM (tramadol hydrochloride).
Source: FDA drug label (Protriptyline Hydrochloride), Epic Pharma, LLC, effective July 25, 2023 (SPL set c6c7c39e-e510-4f4a-bf7a-926f0e075d3a), via openFDA; the full label on DailyMed
What does the tramadol label say about protriptyline?
Tramadol's label does not name protriptyline itself; it warns about its class (Tricyclic antidepressants):
Tramadol label, warnings and precautionsSyndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported with the use of tramadol products, including tramadol hydrochloride extended-release tablets, particularly during concomitant use with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that …
Tramadol label, warnings and precautionsCases of serotonin syndrome, a potentially life-threatening condition, have been reported with the use of tramadol products, including Tramadol Hydrochloride Extended-Release Capsules, particularly during concomitant use with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g. …
Source: FDA drug label (TRAMADOL HYDROCHLORIDE), Lupin Pharmaceuticals, Inc., effective March 5, 2026 (SPL set 46bb9ae6-3ee8-463c-badb-c7a45a89b84b), 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
| Protriptyline | Tramadol | |
|---|---|---|
| Labeled for | Depression | Pain |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $2.71 per tablet 10 mg tablet | $0.0248 per tablet 50 mg tablet |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once