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Drug Interactions with St John’s Wort Mechanisms and Clinical Implications

Drug Interactions with St John’s Wort Mechanisms and Clinical Implications

  1. NeuroChi
    Drug Interactions with St John’s Wort
    Mechanisms and Clinical Implications

    Marcus Mannel
    Ad libitum Medical Services, Berlin, Germany

    The purpose of this paper is to review preclinical and clinical evidence relating
    to drug interactions with preparations of the medicinal herb St John’s wort
    (Hypericum perforatum). A systematic literature search was carried out in three
    electronic databases up to June 2004. Information about case reports classified as
    St John’s wort drug interactions was retrieved from the WHO Collaborating
    Centre for International Drug Monitoring and from the UK Medicines and
    Healthcare products Regulatory Agency in June 2003.
    Against the background of proven efficacy in mild to moderate depressive
    disorders and an excellent tolerability profile in monotherapy, there is sufficient
    evidence from interaction studies and case reports to suggest that St John’s wort
    may induce the cytochrome P450 (CYP) 3A4 enzyme system and the
    P-glycoprotein drug transporter in a clinically relevant manner, thereby reducing
    efficacy of co-medications. Drugs most prominently affected and contraindicated
    for concomitant use with St John’s wort are metabolised via both CYP3A4 and
    P-glycoprotein pathways, including HIV protease inhibitors, HIV non-nucleoside
    reverse transcriptase inhibitors (only CYP3A4), the immunosuppressants
    ciclosporin and tacrolimus, and the antineoplastic agents irinotecan and imatinib
    mesylate. Efficacy of hormonal contraceptives may be impaired as reflected by
    case reports of irregular bleedings and unwanted pregnancies. Drugs with a
    narrow therapeutic index should be monitored more closely when St John’s wort
    is added, discontinued or the dosage is changed. The St John’s wort constituent
    hyperforin is probably responsible for CYP3A4 induction via activation of a
    nuclear steroid/pregnane and xenobiotic receptor (SXR/PXR) and hypericin may
    be assumed to be the P-glycoprotein inducing compound, although the available
    evidence is less convincing.
    Combinations of St John’s wort with serotonergic agents and other antidepressants
    should be restricted to prescription-only, by experienced clinicians, due to
    potential central pharmacodynamic interactions.
    In conclusion, providing certain precautions and contraindications are followed,
    and adequate information is given to healthcare professionals and patients,
    the safe and effective use of quality-tested St John’s wort products can be ensured.