MESSAGE FROM PROFESSOR A BRECKENRIDGE
CHAIRMAN, COMMITTEE ON SAFETY OF MEDICINES.

29 FEBRUARY 2000
CEM/CMO/2000/4

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Dear Doctor

IMPORTANT INTERACTIONS BETWEEN ST JOHN'S WORT (HYPERICUM PERFORATUM) PREPARATIONS AND PRESCRIBED MEDICINES

This is to inform you of new evidence of important interactions between St John's Wort (Hypericum perforatum) preparations and certain prescribed medicines leading to loss of therapeutic effect of the prescribed medicines. St John's Wort (SJW) preparations are unlicensed herbal remedies. Their levels of active ingredients can vary from one preparation to another. They are available from pharmacies, health food shops and herbal practitioners. Because St John's Wort preparations are so widely available, your patients may be taking them without your knowledge. This letter and the enclosed Fact Sheets summarise the Committee on Safety of Medicines' (CSM) advice and provide guidance on management of patients.

New evidence suggests that preparations of St John's Wort are inducers of various drug metabolising enzymes. This may result in a reduction in blood levels and therapeutic effect of some medicines metabolised by these enzymes. Because levels 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. It is important to note that when patients stop taking a preparation containing St John's Wort, blood levels of interacting medicines may rise resulting in toxicity. CSM has advised that St John's Wort should not be used with the following medicines:

• indinavir
• warfarin
• cyclosporin
• oral contraceptives
• digoxin
• theophylline

Although there is no direct evidence, clinically important interactions are also likely with:

• other HIV protease inhibitors (saquinavir, ritonavir, nelfinavir)
• HIV non-nucleoside reverse transcriptase inhibitors (efavirenz, nevirapine)
• anticonvulsants (phenytoin, carbamazepine, phenobarbitone)

Furthermore, St John's Wort preparations affect neurotransmitters in the brain and may interact with psychotropic medicines including Selective Serotonin Reuptake Inhibitors (SSRIs). St John's Wort preparations may also have pharmacodynamic interactions with triptans used to treat migraine. These interactions may result in serious adverse reactions.

Patients already taking these prescribed medicines should not take St John's Wort. Doctors and pharmacists are advised to ask patients about use of non-prescription medicines including herbal remedies. Specific advice on dealing with the interactions listed above is given in Table 1 of the attached Fact Sheet. Please note that 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. St John's Wort preparations are unlikely to interact with topical medicines with limited systemic absorption and non-psychotropic medicines which are excreted renally.

Suspected interactions with St John's Wort preparations should be reported to the Medicines Control Agency/Committee on Safety of Medicines through the Yellow Card Scheme. Yellow Cards are available in the back of the British National Formulary.

For further information, please call the Medicines Control Agency on 0171 273 0000.

Yours faithfully

Professor A Breckenridge