Drug & supplement interaction

Evening Primrose + Amitriptyline, Perphenazine

Amitriptyline, Perphenazine brand names: Triavil, Etrafon, Etrafon-A, Etrafon-Forte.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Amitriptyline, Perphenazine falls into 2 drug categories that Evening Primrose can interact with; the most serious is rated moderate. Theoretically, taking evening primrose oil with phenothiazines might increase the risk of convulsions.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Evening Primrose and Amitriptyline, Perphenazine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Evening Primrose interacts with whole categories of medication. Amitriptyline, Perphenazine falls into 2 of those categories, so it can interact with Evening Primrose in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

PHENOTHIAZINES

1 of 2

Why this applies to Amitriptyline, Perphenazine

Amitriptyline, Perphenazine falls under PHENOTHIAZINES — the group Evening Primrose interacts with.

Theoretically, taking evening primrose oil with phenothiazines might increase the risk of convulsions.
Evening primrose oil contains gamma-linolenic acid (GLA). There is some concern that taking supplements containing GLA might cause seizures, or lower the seizure threshold, when taken with phenothiazines. In one report, three patients with schizophrenia who had received phenothiazines developed EEG changes suggestive of temporal lobe epilepsy after starting treatment with GLA, although none experienced an actual seizure. In another report, two patients with schizophrenia who were stabilized on phenothiazines developed seizures when evening primrose oil 4 grams daily was added. One of these patients had a prior history of seizures. It is unclear whether evening primrose oil had any additive epileptogenic effects with the phenothiazines; there is no evidence that taking evening primrose oil alone causes seizures.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Your medication combines amitriptyline (a tricyclic antidepressant) with perphenazine, which is a phenothiazine. Here's the concern: phenothiazines can already lower the seizure threshold a little, meaning the brain becomes slightly more prone to a seizure. There's a worry that the GLA in evening primrose oil might add to that effect when the two are taken together.

I want to be honest about how thin this evidence is. It comes from just a few older case reports, not solid studies, so it's largely theoretical. On its own, evening primrose doesn't seem to cause seizures. Still, since your medicine carries some seizure risk, it's worth a quick chat with your pharmacist or doctor before adding the supplement, especially if you've ever had a seizure.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Holman CP and Bell AF. A trial of evening primrose oil in the treatment of chronic schizophrenia. J Orhtomolecular Psych 1983;12:302-304.
  2. Vaddadi KS. The use of gamma-linolenic acid and linoleic acid to differentiate between temporal lobe epilepsy and schizophrenia. Prostaglandins Med 1981;6(4):375-379. PubMed
  3. Puri BK. The safety of evening primrose oil in epilepsy. Prostaglandins Leukotrienes Essential Fatty Acids 2007;77:101-3. PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 2

Amitriptyline, Perphenazine also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, evening primrose may increase the levels and clinical effects of CYP2C9 substrates.
In vitro research shows that linoleic acid, a constituent of evening primrose oil, inhibits CYP2C9.
Severity Minor Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

This combo pill pairs amitriptyline (a tricyclic antidepressant) with perphenazine (an antipsychotic). The concern here is mostly theoretical. A fatty acid found in evening primrose oil (linoleic acid) was shown in lab dish studies to slow down an enzyme called CYP2C9, which helps the body break down certain medicines. If that happened in real life, levels of your medication could creep up a bit.

What that could feel like: more of the usual side effects, such as drowsiness, dry mouth, constipation, blurry vision, dizziness when standing, or a faster heartbeat. Honestly, though, this is based only on test-tube data, not on people, so the real-world risk looks small. Please don't stop or change anything on your own. Just mention the evening primrose to your pharmacist or doctor so they can keep an eye on you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zou L, Harkey MR, and Henderson GL. Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity. Life Sci 8-16-2002;71(13):1579-1589. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Evening Primrose Also Interacts With Other Medications

Evening Primrose has 147 moderate, 85 minor known drug interactions in our database — the Amitriptyline, Perphenazine one above is among them. If you take anything else, check it against the full list below.

Moderate 147 Minor 85 No known interaction 2,598 (incl. Amitriptyline, Perphenazine)
Taking anything else?

Check Another of Your Medications Against Evening Primrose

Covers the 2,830 medications we’ve checked against Evening Primrose. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Amitriptyline, Perphenazine

This page covers Evening Primrose only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline, Perphenazine page lists 311 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 19 major · 235 moderate · 57 minor.

From our pharmacist’s overview on the Amitriptyline, Perphenazine page

“Alcohol is the risk I'd flag first for anyone taking amitriptyline with perphenazine (Triavil, Etrafon). Beer and wine both carry major ratings here, and 78 of the 311 ingredients on file deepen the drowsiness this antidepressant and antipsychotic combination already causes, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline, Perphenazine interaction page

One more smart check

Taking Evening Primrose as Part of a Dietary Supplement Product? Check It for Interactions

We hold 98 real supplement products containing Evening Primrose, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Evening Primrose. Your product may carry other ingredients that interact with Amitriptyline, Perphenazine too, on top of Evening Primrose — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Evening Primrose and Amitriptyline, Perphenazine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Evening Primrose
Top half

#695 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Amitriptyline, Perphenazine
Steady interest

#1,786 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Evening Primrose

What is Evening Primrose?

Evening Primrose
  • Eczema and skin health
  • PMS symptoms
  • Breast pain (mastalgia)
  • Menopause symptoms
  • Inflammation
  • Diabetic nerve pain

Evening primrose oil is a seed oil rich in gamma-linolenic acid (GLA), an omega-6 fatty acid, that is popularly used for skin conditions, PMS, and breast pain. The evidence behind most of these uses is mixed or weak, and it is not proven to be a reliable treatment for any condition. It is generally well tolerated for short-term use, but talk to your pharmacist or doctor before starting it, especially if you are pregnant or have a bleeding disorder.

Read the full Evening Primrose monograph & all interactions
Keep checking

Other Drugs & Evening Primrose

Browse every other medication we’ve checked against Evening Primrose — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
147Moderate
85Minor
2,597No known interaction
147 Moderate 85 Minor 2,597 No interaction
Moderate

147 interactions

Showing 60 of 147 moderate interactions — see all 147 on the Evening Primrose page.

Minor

85 interactions

Showing 60 of 85 minor interactions — see all 85 on the Evening Primrose page.

No interaction 2,597 drugs checked — show the list

We also checked Evening Primrose against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,597 medications checked with no known interaction — see the full Evening Primrose list.

See the full Evening Primrose interactions page
See every supplement checked against Amitriptyline, Perphenazine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Evening Primrose monograph › Uses, safety, and every drug interaction in one place Amitriptyline, Perphenazine supplement interactions › Every supplement checked against Amitriptyline, Perphenazine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Evening Primrose and Amitriptyline, Perphenazine Together: Common Questions

Can you take Evening Primrose with Amitriptyline, Perphenazine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Evening Primrose and Amitriptyline, Perphenazine?
Amitriptyline, Perphenazine belongs to more than one drug category, and Evening Primrose interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Evening Primrose and Amitriptyline, Perphenazine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.