The Therapeutic Goods Administration (TGA) wishes to alert doctors, pharmacists and complementary health practitioners to emerging evidence of important interactions between St John's Wort (Hypericum perforatum) preparations and some prescribed medicines. Particularly important are interactions which may lead to loss of therapeutic effect of the prescribed medicines.
St John's Wort is an ingredient in many complementary medicines which are available without prescription from pharmacies, health food shops, supermarkets and complementary medicine practitioners. The content of St John's Wort varies from one product to another. Because St John's Wort preparations are so widely available, patients may be taking them without their health practitioner's knowledge.
The accompanying Information Sheet for Health Professionals summarises the advice received by the TGA from the Adverse Drug Reactions Advisory Committee (ADRAC) and the Complementary Medicines Evaluation Committee (CMEC) and provides guidance on the management of patients.
It appears that preparations of St John's Wort may be inducers of various drug metabolising enzymes. This may result in a reduction in the plasma concentrations and therapeutic effects of medicines metabolised by these enzymes. Because amounts of active ingredients can vary from one preparation of St John's Wort to another, and patients may switch between preparations, the degree of induction is likely to vary.
There is strong evidence to suggest that St John's Wort significantly reduces the plasma concentrations of the following medicines:
- indinavir
- cyclosporin
There are also reasonable grounds for concern that St John's Wort may reduce the efficacy of the following medicines:
- warfarin
- digoxin
- theophylline
- other HIV protease inhibitors (saquinavir, ritonavir, nelfinavir)
- HIV non-nucleoside reverse transcriptase inhibitors (efavirenz, nevirapine, delavirdine)
- anticonvulsants (phenytoin, carbamazepine, phenobarbitone)
The evidence to support these concerns ranges from specific clinical studies to reports of individual cases or is based on theoretical considerations.
Oral Contraceptives ("the pill") may be affected by the enzyme induction of St John's Wort. Some episodes of breakthrough bleeding reported overseas have been attributed to the interaction. Unintended pregnancy has not been reported but, given the mechanism involved, there are grounds for concern that the interaction might reduce the contraceptive efficacy of some oestrogen-containing Oral Contraceptives.
In addition, St John's Wort products may affect neurotransmitters in the brain and, through this different mechanism, interact with psychotropic medicines including the reuptake inhibitor nefazodone and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. St John's Wort preparations may also have similarly-based interactions with other medicines which affect CNS serotonin concentrations such as the various triptans used to treat migraine. These interactions may result in adverse reactions consistent with excess CNS serotonin concentrations and may be severe.
Specific advice on dealing with patients who are already taking St John's Wort and one of the medicines listed above is given in the Information Sheet. It is important to note that when patients stop taking a preparation containing St John's Wort, plasma concentrations of interacting medicines may rise and result in toxicity. The list of medicines is not exhaustive. The actions of many other drugs depend on their route and rate of metabolism and thus other drugs may also interact with St John's Wort preparations. Doctors and pharmacists are urged to ask patients about use of non-prescription medicines including complementary medicines.
To date, one case of the interaction with cyclosporin and six cases of the interaction with reuptake inhibitor drugs have been reported in Australia. Practitioners are encouraged to report suspected interactions with St John's Wort preparations to the Adverse Drug Reactions Advisory Committee using the postage pre-paid blue cards, distributed with the Schedule of Pharmaceutical Benefits booklet and the Australian Adverse Drug Reactions Bulletin. Additional cards can be requested by telephoning 02-62328386.
A copy of the information sheet is available on the TGA website.
The TGA acknowledges the recently distributed advice of the United Kingdom Committee on Safety of Medicines.
Contact for media enquiries:
Dr J McEwen
Director
Adverse Drug Reactions Unit
02 6232 8113