St John's Wort (Hypericum perforatum): A Botanical Guide

St John's Wort is not a gentle, inert botanical. It is a potent inducer of several of the liver enzymes and transport proteins the body uses to clear medicines, which means it can substantially lower the blood levels of drugs you depend on. The UK regulator, the MHRA, has issued repeated safety communications about it, and the EMA herbal monograph lists formal contraindications. Everything below is drawn from those sources.

The mechanism, briefly

According to the EMA herbal monograph on Hypericum perforatum L., herba, hypericum dry extract induces the activity of the cytochrome P450 enzymes CYP3A4, CYP2C9 and CYP2C19, and the transport protein P-glycoprotein. Induction of CYP1A2 has also been reported in the wider literature. "Induction" means the body makes more of these enzymes and transporters, so it clears affected drugs faster and their plasma concentrations fall — sometimes far enough for the drug to stop working.

CYP3A4 alone is involved in the metabolism of a very large share of prescription medicines. So the practical rule is short: if you take any prescription medicine at all, check with your pharmacist before taking St John's Wort. Do not try to work it out from a list.

Do not take St John's Wort if you are taking any of these

The EMA monograph lists concomitant use of the following as a contraindication:

• Ciclosporin (cyclosporine) and tacrolimus for systemic use — including after organ transplant.
• HIV protease inhibitors — amprenavir, indinavir and others.
• Irinotecan, imatinib and other cytostatic (anticancer) agents.
• Warfarin.

It is also contraindicated in anyone with a known hypersensitivity to the plant.

Hormonal contraception

This is the interaction that reaches the most people, and it is why the MHRA has communicated on St John's Wort directly to the public.

The MHRA advice is that women taking hormonal contraceptives to prevent pregnancy should not take products containing St John's Wort.

St John's Wort reduces the plasma concentration of hormonal contraceptives. The EMA monograph states this may lead to increased intermenstrual bleeding — breakthrough bleeding — and reduced safety in birth control, and that women using hormonal contraceptives should take additional contraceptive measures. MHRA reporting has recorded suspected adverse reactions between hormonal contraceptives and St John's Wort resulting in both unplanned pregnancies and breakthrough bleeding without pregnancy, including in women using etonogestrel implants. The MHRA advice is that women taking hormonal contraceptives to prevent pregnancy should not take products containing St John's Wort.

This applies across hormonal methods — combined pill, progestogen-only pill, patch, ring, implant and injection. Data are lacking for non-hormonal intrauterine devices. If you use hormonal contraception, do not take this product without speaking to your prescriber first.

Antiepileptic medicines

The MHRA has published specific advice that concomitant use of St John's Wort and antiepileptic medicine is not recommended, and that healthcare professionals should advise people with epilepsy not to use products containing St John's Wort. Reported cases have involved levetiracetam, lamotrigine and clobazam, and the advice extends to all antiepileptic medicines. Loss of seizure control is a serious outcome. Do not take this product if you take antiepileptics.

SSRIs, triptans and other serotonergic medicines

The EMA monograph notes that hypericum dry extract may contribute to serotonergic effects when combined with serotonin reuptake inhibitors such as sertraline and paroxetine, with nefazodone, with buspirone, or with triptans. It records that, very rarely, undesired effects consistent with serotonin syndrome can occur in combination with serotonin-uptake inhibitors or other serotonergic active substances — with autonomic features such as perspiration, tachycardia, diarrhoea and fever; mental features such as agitation and disorientation; and motor features such as tremor or myoclonus.

Other serotonergic medicines commonly cited in this context include SNRIs, MAO inhibitors, tramadol and linezolid. If you take any medicine acting on serotonin, do not take St John's Wort without your prescriber's agreement.

Anticoagulants and cardiovascular medicines

Concomitant warfarin is contraindicated in the EMA monograph. Reduced anticoagulant effect has been recorded with concomitant use, and reduced effect of the related anticoagulant phenprocoumon is also documented. Digoxin is named in the EMA monograph among the drug substances whose plasma concentrations may be reduced; the published literature describes clinically meaningful falls in digoxin levels. Simvastatin is also named. If you take an anticoagulant, an antiarrhythmic or a statin, check first.

Transplant and immunosuppressant medicines

Ciclosporin is the best-documented and most serious case. Published transplant studies found St John's Wort altered ciclosporin pharmacokinetics within days and reduced exposure substantially in every patient studied, and organ rejection episodes have been reported where ciclosporin concentrations fell below the therapeutic range. Tacrolimus for systemic use is likewise contraindicated. If you have had a transplant, or take any immunosuppressant, do not take this product.

HIV antiretrovirals

The EMA has issued a public statement on the risk of drug interactions between Hypericum perforatum and antiretroviral medicinal products. St John's Wort induces CYP3A4, lowering antiretroviral plasma levels and reducing their therapeutic effect; sub-therapeutic concentrations can lead to the development of resistance and treatment failure. The EMA's position is that patients treated with indinavir — and by extrapolation other antiretroviral medicinal products for HIV-1 infection — should not take products containing Hypericum perforatum. This covers protease inhibitors and non-nucleoside reverse transcriptase inhibitors.

Other medicines named in the EMA monograph

The monograph advises special care with all drug substances metabolised via CYP3A4, CYP2C9, CYP2C19 or P-glycoprotein, because a reduction in plasma concentrations is possible. It gives these worked examples:

• Amitriptyline
• Fexofenadine
• Benzodiazepines
• Methadone
• Simvastatin
• Digoxin
• Finasteride

Theophylline and anticonvulsant medicines are additionally well documented in the wider clinical literature as being cleared faster in the presence of St John's Wort. This list is illustrative, not exhaustive. The monograph's own closing instruction is that patients taking other medicines on prescription should consult a doctor or pharmacist before taking hypericum.

Sunlight and photosensitivity

The EMA monograph states that during use, intense UV exposure should be avoided. It records that fair-skinned individuals may react with dysaesthesia — tingling, sensitivity to cold or pain, a burning sensation — and with intensified sunburn-like symptoms under intense sunlight.

In practice: be cautious with strong sun, avoid sunbeds and UV lamps, and take normal sun protection seriously, particularly if you are fair-skinned or spending long periods outdoors. Photosensitivity of this kind is reported as reversible on stopping.

Pregnancy, breastfeeding and fertility

The EMA monograph is unambiguous: safety during pregnancy and breast-feeding has not been established, studies in animals have shown signs of reproductive toxicity, and use is not recommended during pregnancy and lactation. No fertility data are available. Do not take this product if you are pregnant, trying to conceive or breastfeeding.

Children and adolescents

The EMA monograph states that use in children and adolescents under 18 years of age is not recommended, because sufficient data are not available. This product is for adults.

Duration of use

The EMA monograph frames traditional oral use of hypericum as short-term, and its statement that no clinically relevant interactions are to be expected is confined to preparations delivering 1mg or less of hyperforin daily and a duration of use of no longer than two weeks. As set out above, our extract does not declare a hyperforin content, so that exemption should not be assumed to apply. If you intend to use St John's Wort on an ongoing basis, that is a conversation to have with your doctor or pharmacist rather than a decision to take alone.

Before surgery

The EMA monograph advises that prior to elective surgery, possible interactions with products used during general and regional anaesthesia should be identified, and that the product should be discontinued if necessary. Tell your surgeon, anaesthetist and pre-operative assessment team that you are taking St John's Wort — well in advance, not on the day. A commonly given practical margin in the anaesthetic literature is to stop herbal products around two weeks before surgery, but the decision should be your clinical team's, not ours.

Stopping matters as much as starting

This point is widely missed. Because St John's Wort works by inducing enzymes, stopping it lets those enzyme levels fall back — and the blood levels of any affected medicine rise again, potentially into a range that is too high. The EMA monograph states that elevated enzyme activity returns to normal within one week after cessation. Published work on transplant patients found recovery took longer than two weeks in most of those studied, so individual variation is real.

The practical rule: never start or stop St John's Wort alongside a prescribed medicine without telling the person who prescribes it. An abrupt stop can be as clinically significant as an abrupt start.

Reported undesirable effects

The EMA monograph lists, at unknown frequency: gastrointestinal disorders such as nausea, abdominal pain and diarrhoea; allergic skin reactions; fatigue; and restlessness. Fair-skinned individuals may experience the photosensitivity reactions described above. If any other adverse reaction occurs, consult a doctor or pharmacist.

Driving and machinery

The EMA monograph notes that no adequate studies on the effect on the ability to drive and use machines have been performed.

Overdose

The monograph records that after intake of up to 4.5g of dry extract per day for two weeks, plus a single 15g dose, seizures and confusion have been reported. It advises that after ingestion of massive overdoses the patient should be protected from sunlight and other UV-light sources for one to two weeks. Stay within the label serving.

When to speak to a pharmacist

Speak to a pharmacist or your doctor before taking this product if any of the following apply:

• You take any prescription medicine at all, including ones not named on this page.
• You use any form of hormonal contraception.
• You have epilepsy, or take antiepileptic medicine.
• You take an SSRI, an SNRI, an MAO inhibitor or any other medicine acting on serotonin.
• You take an anticoagulant, digoxin, theophylline, a statin or an immunosuppressant.
• You are being treated for HIV or cancer, or have had a transplant.
• You are pregnant, breastfeeding or trying to conceive.
• You have surgery or a general anaesthetic scheduled.
• You are under 18.
• You are under the care of any medical or healthcare professional.

Community pharmacists in the UK can check your full medicines list against St John's Wort in a couple of minutes, free of charge, without an appointment. Worth the trip.

Reporting side effects

Suspected adverse reactions to herbal products can be reported to the MHRA through the Yellow Card Scheme. Reporting is how several of the interactions described on this page — including the hormonal contraceptive and antiepileptic interactions — were first identified.

Sources consulted for this section: the EMA herbal monograph on Hypericum perforatum L., herba (EMA/HMPC/7695/2021); the EMA public statement on the risk of drug interactions with Hypericum perforatum and antiretroviral medicinal products; MHRA Drug Safety Update guidance on St John's Wort and antiepileptics and on herbal medicines and the Yellow Card Scheme; and the peer-reviewed clinical pharmacology literature on hypericum drug interactions.