Herb-Drug Interactions: Feverfew

Tanacetum parthenium Sch.Bip. (Asteraceae)

Synonym(s) and related species

Altamisa, Featherfew, Featherfoil, Midsummer daisy.

Chrysanthemum parthenium (L.) Bernh., Leucanthemum parthenium (L.) Gren & Godron, Pyrethrum parthenium (L.) Sm.

Pharmacopoeias

Feverfew (British Ph 2009, European Ph 2008, US Ph 32); Powdered Feverfew (The United States Ph 32).

Constituents

The leaf and aerial parts contain sesquiterpene lactones, especially parthenolide, its esters and other derivatives, santamarin, reynosin, artemorin, partholide, chrysanthemonin and others. The volatile oil is composed mainly of alpha-pinene, bornyl acetate, bornyl angelate, costic acid, camphor and spirotekal ethers.

Use and indications

Feverfew is mainly used for the prophylactic treatment of migraine and tension headache, but it has antiplatelet and anti-inflammatory activity, and has been used for coughs, colds and rheumatic conditions. It can cause allergic and cytotoxic reactions due to the presence of sesquiterpene lactones with an alpha-methylene butyrolactone ring, as in parthenolide.

Pharmacokinetics

In a study investigating the in vitro inhibitory potency of an extract of feverfew using a commercially available mixture of cytochrome P450 isoenzymes, and established substrates of these isoenzymes, the feverfew extract modestly inhibited the activity of CYP1A2, CYP2C8, CYP2C9, CYP2C19 and CYP3A4. The findings of in vitro studies cannot be directly extrapolated to humans, but positive findings such as these suggest that further study is required.

In an in vitro study, the transport of parthenolide, a constituent of feverfew, was not affected by the presence of MK-571, an inhibitor of P-glycoprotein.

Interactions overview

Feverfew inhibits platelet aggregation in vitro and, theoretically, might increase the risk of bleeding in patients taking other drugs that increase bleeding such as aspirin or anticoagulants.

Feverfew + Anticoagulants

The interaction between feverfew and anticoagulants is based on a prediction only.

Evidence, mechanism, importance and management

The manufacturer advises that feverfew as a herbal medicine may theoretically interact with warfarin and increase the risk of bleeding on the basis of its in vitro antiplatelet effects (see Feverfew + Antiplatelet drugs, below). However, they note that the clinical relevance of this in vivo is unknown. Some reviews also note this potential for an interaction and suggest that concurrent use should be avoided. Clinically the use of an antiplatelet drug with an anticoagulant should generally be avoided in the absence of a specific indication. It may therefore be prudent to advise against concurrent use. However, if concurrent use is felt desirable, the risks and benefits of treatment should be considered. It would seem sensible to warn patients to be alert for any signs of bruising or bleeding, and report these immediately, should they occur.

Feverfew + Antiplatelet drugs

Feverfew inhibits platelet aggregation in vitro and, theoretically, might have additive effects with conventional antiplatelet drugs.

Clinical evidence

A letter briefly describes a study in which platelet aggregation was assessed in samples taken from 10 patients who had taken feverfew for at least 3.5 years. The platelets aggregated normally in response to thrombin and ADP; however, the response to serotonin and U46619 (a thromboxane mimetic) was attenuated, and occurred only at higher doses.

Experimental evidence

In a number of early in vitro studies, mostly by the same research group, feverfew was found to inhibit platelet aggregation. In these studies, feverfew extracts inhibited ADP, thrombin and collagen-induced platelet aggregation, and inhibited the uptake and release of arachidonic acid… Parthenolide, a constituent of feverfew, has also been shown to inhibit platelet aggregation in vitro*

Mechanism

Unclear. It was suggested that the mechanism of platelet inhibition is

neutralisation of sulfhydryl groups within the platelets, although the exact sulfhydryl groups involved still need to be defined.

Importance and management

There appears to be only one clinical study, which does not wholly substantiate the in vitro findings that feverfew inhibits platelet aggregation in response to certain chemical stimuli. However, the study does support the finding of somewhat reduced platelet responsiveness. It could be argued that any interaction should have come to light by now, since feverfew has been in fairly widespread use for the management of migraines, and, in this setting, it is likely to have been taken with aspirin and NSAIDs. On the other hand, the small increased risk of bleeding with low-dose aspirin has required very large retrospective comparisons to establish. Concurrent use need not be avoided (indeed combinations of antiplatelet drugs are often prescribed together) but it may be prudent to be aware of the potential for increased bleeding if feverfew is given with other antiplatelet drugs such as aspirin and clopidogrel. Patients should discuss any episode of prolonged bleeding with a healthcare professional.

Feverfew + Food

No interactions found.

Feverfew + Herbal medicines

No interactions found.