St. John’s wort, interaction with

Beer, A.M., and T. Ostermaim. 2001. St. John s wort Interaction with cyclosporine increases risk of rejection for the kidney transplant and raises daily cost of medication. Med. Klin. 96(8) 480-483. 

TABLE 29.2 Reported Clinically Significant Interactions of St. John s Wort (SJW) with Prescription Drugs... 

Maurer A, Johne A, Bauer S, Brockmoller J, Donalh F, Roots I, Langheinrich M, Hubner W-D. Interaction of St John s wort extract with phenprocoumon EurJ Clin Pharmacol (1999) 55, A22. 

Maurer, A., A. Johne, and S. Bauer. 1999. Interaction of St. John s wort extract with phenprocoumon [abstract]. Eur.. Clin. Pharmacol. 55 A22. 

A. Johne, J. Brockmoller, S. Bauer, A. Maurer, M. Langheinrich, and I. Root, Pharmacokinetic interaction of digoxin with an herbal extract from St. John s wort (Hypericum perforatum). Clin. Pharmacol. Ther., 66, 338-345 (1999). 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

In addition to this serious diet-drug interaction, irreversible MAOIs also potentiate the effects of sympathomimetic drugs like ephedrine found in over-the-counter cold remedies and recreational stimulants like amphetamine. The MAOIs also interact with drugs that increase synaptic concentrations of 5-HT, such as the tricyclic antidepressant clomipramine and the herbal SSRI antidepressant St John s wort (Hypericum spp.). The resulting serotonin syndrome is characterised by hyperthermia and muscle rigidity. While devoid of these side effects the reversible MAO-A inhibitor moclobemide has yet to establish itself as a first-line alternative to the SSRIs. 

St. John s wort, an herbal nonprescription medication containing hyperi-cum, may be effective for mild to moderate depression, but it is associated with several drug-drug interactions. Its potency, purity, and manufacture are not regulated by the FDA. As depression is a potentially life-threatening disease, all antidepressant treatments should be overseen by a trained healthcare professional. 

Prescribers are advised to consult the package insert of any medication administered concomitantly with hormonal contraceptives, because some medications may decrease the effectiveness of these birth control products. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John s wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding while on oral contraceptives shortly after starting St. John s wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John s wort. 

St John s Wort (Hypericum perforatum, S JW) has been on the herbal pharmacopeia for many years. It is a traditional remedy for depression which has been validated in recent randomized clinical trials. Like many herbal preparations levels of active constituents vary from one preparation to another. As a consequence of its validation as an active preparation it has been widely promoted. Recently it has been shown to interact with a variety of other substances probably through the process of drug interaction. 

Hypericum extracts can have clinically significant interactions with prescribed medications (Rey and Walter, 1998 Ernst, 1999b Piscitelli et ah, 2000 Walter et ah, 2000). The more important interactions known are presented in Table 29.2. There is limited information about the mechanisms involved. The more common view is that St. John s wort extracts activate the... 

Hypericum has been found to also interact with drugs metabolized via other pathways. For example, it decreases serum levels of digoxin, which is metabolized via the P-glycoprotein drug transporter, and reduces levels of theophylline and warfarin, which are metabolized via CYP1A2 and CYP2C9 pathways, respectively. It is possible that St. John s wort might also induce those enzymes via the steroid X receptor (Wentworth et ah, 2000). 

Clinicians should be aware that many of their patients may be taking alternative treatments either via self-care or prescribed by CAM practitioners. Inquiring about this should be routine because of potential side effects and drug interactions. A working knowledge of CAM treatments will allow child psychiatrists to give parents and patients advice about safety and effectiveness. Use of St. John s wort in children with unipolar depression may at times be appropriate, particularly in cases where more standard treatments are contraindicated or have failed. However, it should be used cautiously and with an appropriate explanation of its risks and benefits, as a competent clinician would do for any treatment. Use of St. John s wort for other conditions is not currently recommended given the lack of evidence for efficacy. Kava extracts may be used for anxiety, with similar provisos. There are much fewer data about the efficacy and safety of other dietary supplements and their use cannot be supported at this point. 

Breidenbach T, Hoffmann MW, Becker T, et al Drug interaction of St John s wort with cyclosporin (letter). Lancet 355 1912, 2000... 

Greenblatt DJ, von Moltke LL, Harmatz JS, et al Human cytochromes and some newer antidepressants kinetics, metabolism, and drug interactions. J Clin Psychopharmacol 19 23S-35S, 1999 Karliova M, Treichel U, Malago M, et al Interaction of Hypericum perforatum (St. John s wort) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 33 853-855, 2000 Michalets EL Update clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 18 84-112, 1998... 

The similar pharmacological profile of selective serotonin reuptake inhibitors and St. John s wort would suggest the potential of a pharmacodynamic interaction due to an additive effect. A case of concurrent use of sertraline and St. John s wort, resulting in mania, was reported for a patient with a history of depression who was prescribed sertraline and who also took St. John s wort against medical advice (58). A similar potentiation of serotonergic effect was reported by Gordon (49). 

Drug Interactions with St. John s Wort and Echinacea... 

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