There are multiple interactions reported between these two agents.

Interaction Details

Clozapine is classified as belonging to the following category: Serotonergic Drugs

Theoretically, St. John's wort might inhibit reuptake and increase levels of serotonin, resulting in additive effects with serotonergic drugs.
Concomitant use of serotonergic drugs with St. John's wort can lead to increased adverse effects and increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstriction disorders.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

References

  • Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  • Gordon JB. SSRIs and St. John's Wort: possible toxicity? Am Fam Physician 1998;57:950, 953.
  • Beckman SE, Sommi RW, Switzer J. Consumer use of St. John's wort: A survey of effectiveness, safety, and tolerability. Pharmacotherapy 2000;20:568-74.
  • Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3.
  • Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T

Interaction Details

Clozapine is classified as belonging to the following category: Photosensitizing Drugs

Theoretically, St. John's wort might increase the likelihood for photosensitivity reactions when used in combination with photosensitizing drugs.
St. John's wort might increase photosensitivity reactions due to its hypericin content. However, some clinical research shows that very high doses of St. John's wort are needed to produce phototoxicity in humans.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

References

  • Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  • Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
  • Schempp CM, Muller K, Winghofer B, et al. Single-dose and steady-state administration of Hypericum perfotatum extract (St. John's wort) does not influence skin sensitivity to UV radiation, visible light, and solar-stimulated radiation. Arch Dermatol 2001;
  • Bernd A, Ramirez-Bosca A, Kippenberger S, and et al. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol 1999;2(69):218-221.

Interaction Details

Clozapine is classified as belonging to the following category: Cytochrome P450 1A2 (Cyp1A2) Substrates

St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.
Clinical research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

References

  • Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
  • Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42..
  • Van Strater, A. C. and Bogers, J. P. Interaction of St John's wort (Hypericum perforatum) with clozapine. Int.Clin.Psychopharmacol. 2012;27(2):121-124.

Interaction Details

Clozapine is classified as belonging to the following category: Clozapine (Clozaril)

St. John's wort might decrease the levels and clinical effects of clozapine.
A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort.

Interaction Rating

Moderate

Likelihood of Occurrence

Possible

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

References

  • Soleymani S, Bahramsoltani R, Rahimi R, Abdollahi M. Clinical risks of St John's Wort (Hypericum perforatum) co-administration. Expert Opin Drug Metab Toxicol. 2017;13(10):1047-62.

St. John's Wort Overview

St. John's Wort St. John's wort (Hypericum perforatum) is a plant native to Europe and is known for its medicinal properties. St. John's wort has been used to treat a variety of conditions, including depression, anxiety, and sleep disorders. It is one of the most extensively used and researched natural medicines in the world, and is thought to work similarly to certain conventional antidepressants by increasing the levels of serotonin in the brain.
See More Information Regarding St. John's Wort

Clozapine Overview

  • Clozapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in people who have not been helped by other medications or who have tried to kill themselves and are likely to try to kill or harm themselves again. Clozapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.

See More Information Regarding Clozapine

St. John's Wort - More Interactions

St. John's Wort interacts with 1113 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.

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In addition to being a clinical pharmacist specializing in pharmacotherapy, Dr. Brian Staiger is a registered herbalist through the American Herbalist Guild. He has combined his passion for pharmacy practice with the study of medical ethnobotany to improve patient care. Feel free to reach out about any of your herbal or medication questions!

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