St John's Wort: information sheet for health care professionals

Interactions of St John's Wort (Hypericum perforatum) preparations

13 March 2000

Introduction

Complementary medicines containing St John's Wort (SJW) are regulated by the Therapeutic Goods Administration. Their levels of active ingredients can vary from one preparation to another. They are widely used in the Australia, being available from pharmacies, health food shops, supermarkets and complementary medicine practitioners.

Why do SJW preparations interact with other medicines?

New evidence suggests that SJW preparations may interact with medicines, either by affecting drug metabolism or levels of neurotransmitters. Drug metabolism may be affected by SJW preparations inducing certain cytochrome P450 isoenzymes in the liver (particularly CYP 3A4, but also 1A2 and 2C9), as well as P-glycoprotein. Pharmacodynamic (additive or potentiating) interactions may occur through the effects of SJW preparations on neurotransmitters in the brain (SJW may increase CNS serotonin levels).

What is the clinical significance of these interactions?

Induction of drug metabolism increases the breakdown of some drugs and may reduce their blood levels and therapeutic effects. Because the levels of active ingredients can vary between preparations of SJW and patients may switch between preparations, the degree of induction is likely to change over time. When patients stop taking SJW preparations, blood levels of interacting medicines may rise, possibly leading to toxicity.

Pharmacodynamic (additive or potentiating) interactions may occur with psychoactive medicines including selective serotonin reuptake inhibitors (SSRIs). St John's Wort preparations may also have pharmacodynamic interactions with other medicines which affect serotonin such as other antidepressants and triptans used to treat migraine. These interactions may result in a variety of symptoms such as mental state changes, autonomic dysfunction and motor effects consistent with increased CNS serotonin.

Which medicines interact with SJW?

The table lists medicines where pharmacokinetic studies or spontaneously reported suspected adverse reactions demonstrate clinically important interactions. In addition, other drugs are included where direct evidence is lacking but clinically important interactions are likely. Please note that the action of many other drugs depends on their rate of metabolism and whether or not the metabolites are active compounds, and thus other drugs may also interact with SJW preparations. In general, the following medicines are not likely to interact with SJW preparations:

  • topical medicines with limited systemic absorption (inhalers, skin creams and ointments, eye and ear drops, enemas etc).
  • Non-psychotropic medicines which are principally excreted renally.

Reporting suspected adverse reactions including interactions

If you suspect your patient has had an adverse reaction associated with a SJW preparation, then please report this to ADRAC using the post pre-paid blue cards, distributed with the Schedule of Pharmaceutical Benefits booklet or the Australian Adverse Drug Reactions Bulletin. Additional cards can be requested by telephoning 02-62328386.

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Table - Clinically important interactions of St John's Wort (SJW) - Hypericum perforatum

Patients taking drugs listed in the Table should not start taking SJW preparations

Drug Effect of interaction on drug Suggested management of patients already taking SJW preparations
HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir) Reduced blood levels with possible loss of HIV suppression. Measure HIV RNA viral load and stop SJW.
HIV non-nucleoside reverse transcriptase inhibitors (efavirenz, nevirapine, delavirdine) Reduced blood levels with possible loss of HIV suppression. Measure HIV RNA viral load and stop SJW.
Cyclosporin, tacrolimus Reduced blood levels with risk of transplant rejection. Check cyclosporin or tacrolimus blood levels and stop SJW. Levels may increase on stopping SJW. The dose may need adjusting.
Warfarin Reduced anticoagulant effect and need for increased warfarin dose. Check INR and stop SJW. Monitor INR closely as this may rise on stopping SJW. The dose of warfarin may need adjusting.
Digoxin Reduced blood levels and loss of control of heart rhythm or heart failure. Check digoxin levels and stop SJW. Digoxin levels may increase on stopping SJW. The dose of digoxin may need adjusting.
Theophylline Reduced blood levels and loss of bronchodilator effect. Check theophylline levels and stop SJW. Theophylline levels may increase on stopping SJW. The dose of theophylline may need adjusting.
Anticonvulsants (carbamazepine, phenobarbitone, phenytoin) Reduced blood levels with risk of seizures. Check anticonvulsant levels and stop SJW. Anticonvulsant levels may increase on stopping SJW. The dose of anticonvulsant may need adjusting.
Oral contraceptives Reduced blood levels with risk of breakthrough bleeding. Possible contraceptive failure (see TGA Alert). Weigh the benefits of continuing SJW against possible reduced contraceptive efficacy.
SSRIs and related drugs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, nefazodone) Increased serotonergic effects with increased chance of adverse reactions. Weigh the benefits of continuing SJW against possible adverse effects.
Triptans (sumatriptan, naratriptan, rizatriptan, zolmitriptan) Increased serotonergic effects with increased chance of adverse reactions. Weigh the benefits of continuing SJW against possible adverse effects.

Note: The action of many other drugs depends on their rate of metabolism and thus other drugs may also interact with St John's Wort preparations.