Evening Primrose - Amitriptyline, Perphenazine Interaction
Herbal: Evening Primrose
Also Known As: Oenothera biennis, Oenothera muricata, Oenothera rubricaulis, Evening star, Suncups, Sundrop
Drug: Amitriptyline, Perphenazine
Brand names:
Triavil, Etrafon, Etrafon-A, Etrafon-Forte

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
May 11, 2025
Interaction Details
Amitriptyline, Perphenazine is classified as belonging to the following category: 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.
Interaction Rating
Likelihood of Occurrence
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
References
- 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.
Interaction Details
Amitriptyline, Perphenazine is classified as belonging to the following category: Phenothiazines
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.
Interaction Rating
Likelihood of Occurrence
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
References
- Holman CP and Bell AF. A trial of evening primrose oil in the treatment of chronic schizophrenia. J Orhtomolecular Psych 1983;12:302-304.
- 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.
- Puri BK. The safety of evening primrose oil in epilepsy. Prostaglandins Leukotrienes Essential Fatty Acids 2007;77:101-3.
Evening Primrose Overview

Evening Primrose - More Interactions
Evening Primrose interacts with 229 drugs
Interaction Rating Key
These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.
Major | The combined use of these agents is strongly discouraged as serious side effects or other negative outcomes could occur. |
Moderate | Use cautiously under the care of a healthcare professional or avoid this combination. A significant interaction or negative outcome could occur. |
Minor | Be aware that there is a chance of an interaction. Watch for warning signs of a potential interaction. |
Unknown | No interactions have been reported or no interaction data is currently available. |
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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
Drug descriptions are provided by MedlinePlus.