St John's Wort: information sheet for health care professionals

Interactions of St John's Wort (Hypericum perforatum) preparations

13 March 2000

Introduction

Why do SJW preparations interact with other medicines?

What is the clinical significance of these interactions?

Which medicines interact with SJW?

Reporting suspected adverse reactions including interactions

Table - Clinically important interactions of St John's Wort (SJW)

Introduction

Complementary medicines containing St John's Wort (SJW) are regulated by the Therapeutic Goods
Administration. Their levels of active ingredients can vary from one preparation to another. They are
widely used in the Australia, being available from pharmacies, health food shops, supermarkets and
complementary medicine practitioners.

Why do SJW preparations interact with other medicines?

New evidence suggests that SJW preparations may interact with medicines, either by affecting drug
metabolism or levels of neurotransmitters. Drug metabolism may be affected by SJW preparations
inducing certain cytochrome P450 isoenzymes in the liver (particularly CYP 3A4, but also 1A2 and 2C9),
as well as P-glycoprotein. Pharmacodynamic (additive or potentiating) interactions may occur through
the effects of SJW preparations on neurotransmitters in the brain (SJW may increase CNS serotonin
levels).

What is the clinical significance of these interactions?

Induction of drug metabolism increases the breakdown of some drugs and may reduce their blood levels
and therapeutic effects. Because the levels of active ingredients can vary between preparations of SJW
and patients may switch between preparations, the degree of induction is likely to change over time.
When patients stop taking SJW preparations, blood levels of interacting medicines may rise,
possibly leading to toxicity.
Pharmacodynamic (additive or potentiating) interactions may occur with psychoactive medicines
including selective serotonin reuptake inhibitors (SSRIs). St John's Wort preparations may also have
pharmacodynamic interactions with other medicines which affect serotonin such as other antidepressants
and triptans used to treat migraine. These interactions may result in a variety of symptoms such as mental
state changes, autonomic dysfunction and motor effects consistent with increased CNS serotonin.

Which medicines interact with SJW?

The table lists medicines where pharmacokinetic studies or spontaneously reported suspected adverse
reactions demonstrate clinically important interactions. In addition, other drugs are included where direct
evidence is lacking but clinically important interactions are likely. Please note that the action of many
other drugs depends on their rate of metabolism and whether or not the metabolites are active
compounds, and thus other drugs may also interact with SJW preparations. In general, the following
medicines are not likely to interact with SJW preparations:

topical medicines with limited systemic absorption (inhalers, skin creams and ointments,
eye and ear drops, enemas etc).

Non-psychotropic medicines which are principally excreted renally.

Reporting suspected adverse reactions including interactions

If you suspect your patient has had an adverse reaction associated with a SJW preparation, then please
report this to ADRAC using the post pre-paid blue cards (//www.tga.gov.au/reporting-problems), distributed
with the Schedule of Pharmaceutical Benefits booklet or the Australian Adverse Drug Reactions Bulletin.
Additional cards can be requested by telephoning 02-62328386.

Table - Clinically important interactions of St John's Wort (SJW) -

Hypericum perforatum

Patients taking drugs listed in the Table should not start taking SJW preparations

Drug Effect of interaction on drug Suggested management

of patients already
taking SJW preparations

HIV protease Reduced blood levels with possible loss of Measure HIV RNA viral
inhibitors HIV suppression. load and stop SJW.
(indinavir,
nelfinavir,
ritonavir,
saquinavir)

HIV non- Reduced blood levels with possible loss of Measure HIV RNA viral
nucleoside HIV suppression. load and stop SJW.
reverse
transcriptase
inhibitors
(efavirenz,
nevirapine,
delavirdine)

Cyclosporin, Reduced blood levels with risk of transplant Check cyclosporin or

tacrolimus rejection. tacrolimus blood levels
and stop SJW. Levels may
increase on stopping SJW.
The dose may need
adjusting.

Warfarin Reduced anticoagulant effect and need for Check INR and stop SJW.
increased warfarin dose. Monitor INR closely as this
may rise on stopping SJW.
The dose of warfarin may
need adjusting.

Digoxin Reduced blood levels and loss of control of Check digoxin levels and
heart rhythm or heart failure. stop SJW. Digoxin levels
may increase on stopping
SJW. The dose of digoxin
may need adjusting.

Theophylline Reduced blood levels and loss of Check theophylline levels

bronchodilator effect. and stop SJW.
Theophylline levels may
increase on stopping SJW.
The dose of theophylline
may need adjusting.

Anticonvulsants Reduced blood levels with risk of seizures. Check anticonvulsant

(carbamazepine, levels and stop SJW.
phenobarbitone, Anticonvulsant levels may
phenytoin) increase on stopping SJW.
The dose of
anticonvulsant may need
adjusting.

Oral Reduced blood levels with risk of Weigh the benefits of

contraceptives breakthrough bleeding. Possible continuing SJW against
contraceptive failure (see TGA Alert possible reduced
(//www.tga.gov.au/alert/st-johns-wort-important- contraceptive efficacy.
interactions-between-st-johns-wort-hypericum-
perforatum-preparations-and-prescription-
medicines)).
 SSRIs and related Increased serotonergic effects with Weigh the benefits of
drugs increased chance of adverse reactions. continuing SJW against
(citalopram, possible adverse effects.
fluoxetine,
fluvoxamine,
paroxetine,
sertraline,
nefazodone)

Triptans Increased serotonergic effects with Weigh the benefits of

(sumatriptan, increased chance of adverse reactions. continuing SJW against
naratriptan, possible adverse effects.
rizatriptan,
zolmitriptan)

Note: 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.

Category: Alert/Advisory, Medicines safety

Tags: herbal medicines, antidepressants, oral contraceptives, anticonvulsants
URL: https://www.tga.gov.au/node/598 (https://www.tga.gov.au/node/598)