Feverfew

Parthenolide and other sesquiterpene lactones in feverfew irreversibly inhibit platelet granule secretion by neutralising sulfhydryl groups in platelet membrane proteins. Feverfew extracts also inhibit phospholipase A2, reducing arachidonic acid release and thromboxane B2 synthesis. These antiplatelet mechanisms are additive with anticoagulant drugs, increasing bleeding risk. No pharmacokinetic (CYP) interaction with warfarin has been documented.

Avoid concurrent use of feverfew with anticoagulant or antiplatelet drugs. If combination is unavoidable, monitor INR closely and watch for signs of bleeding. Feverfew should be discontinued at least 2 weeks before any surgical or invasive procedure.

NSAIDs may antagonise the antiplatelet and antimigraine benefits of feverfew by blocking the parthenolide-mediated arachidonic acid pathway. Specifically, salicylates and other NSAIDs compete with parthenolide at platelet sulfhydryl binding sites, blunting feverfew efficacy. Conversely, the combined inhibition of prostaglandin synthesis may increase GI bleeding risk.

Patients using feverfew for migraine prophylaxis should avoid regular NSAID use, which may negate the benefit. If anti-inflammatory or analgesic treatment is needed, discuss alternative options with the prescriber. Monitor for GI side effects if combination is unavoidable.

Additive antiplatelet effects via independent mechanisms: feverfew inhibits platelet sulfhydryl groups and phospholipase A2, while aspirin irreversibly inhibits COX-1 and clopidogrel blocks ADP receptors. The combination produces supraadditive inhibition of platelet aggregation and prolongs bleeding time beyond either agent alone.

Avoid combining feverfew with antiplatelet agents. If a patient requires both, monitor for signs of abnormal bleeding. Due to additive bleeding risk, feverfew should be stopped at least 2 weeks before elective surgery or dental procedures in patients on antiplatelet therapy.

Feverfew inhibits serotonin-induced contraction of vascular smooth muscle and reduces platelet serotonin release via sulfhydryl group neutralisation. Triptans act as 5-HT1B/1D receptor agonists. Both are used for migraine, but via different mechanisms. Concurrent use has not been well studied; potential for additive vasoconstriction is theoretical. No documented pharmacokinetic interaction.

Feverfew is generally used as migraine prophylaxis and triptans as acute treatment; concurrent use for prophylaxis + acute management may occur. Monitor for unusual vascular effects. Advise patients to report any worsening of symptoms or cardiovascular side effects.

In vitro data suggest feverfew extract may inhibit CYP3A4 enzyme activity, potentially reducing the hepatic metabolism of co-administered CYP3A4 substrates. This could increase plasma levels of drugs such as omeprazole (PPI), lovastatin (statin), ketoconazole (antifungal), and amiodarone. Clinical significance at standard feverfew doses is currently unknown, as no human pharmacokinetic studies have been conducted.

Monitor patients on narrow-therapeutic-index CYP3A4 substrates (e.g., amiodarone, certain statins) who initiate or discontinue feverfew supplementation. Alert them to signs of drug toxicity (e.g., muscle pain with lovastatin, QT prolongation with amiodarone). Clinical vigilance is warranted even if the interaction magnitude is uncertain.

Parthenolide and other sesquiterpene lactones in feverfew irreversibly inhibit vascular smooth muscle reactivity and suppress platelet granule release via sulphydryl group neutralization. This antiplatelet mechanism combined with thromboxane B2 and leukotriene B4 inhibition produces additive bleeding risk with heparins. Alteration of coagulation test results and vaginal bleeding has been reported with feverfew use.

Monitor anti-Xa levels in patients on LMWH using feverfew; advise patients on anticoagulants not to start feverfew without physician guidance. Discontinue feverfew at least 2 weeks before surgery or invasive procedures.

Feverfew inhibits serotonin release from platelets and may suppress serotonin-induced contractions in vascular smooth muscle. Combined with serotonin reuptake inhibitors, additive effects on serotonin signaling may occur. Additionally, shared antiplatelet properties increase bleeding risk when combined with SSRIs (which also inhibit platelet serotonin reuptake and have independent antiplatelet effects).

Monitor patients on SSRIs/SNRIs for signs of bleeding (bruising, GI bleeds) if combining with feverfew. Advise about additive serotonin-modulating effects. This combination requires regular clinical review particularly in elderly patients.

Feverfew has documented anxiolytic and mild antidepressant-like effects in animal models, suggesting CNS monoamine activity. Potential pharmacodynamic interaction with MAO inhibitors may enhance their serotonin/norepinephrine-potentiating effects. Shared platelet-inhibitory properties further increase bleeding risk.

Avoid concurrent use of feverfew with MAO inhibitors unless under specialist supervision. Monitor for signs of serotonin syndrome (agitation, tremor, diaphoresis, hyperthermia) and report to prescriber promptly.

Parthenolide has demonstrated anticancer activity via NF-kB inhibition and mitochondrial apoptosis induction in preclinical models. While this suggests potential synergy with some chemotherapy agents, parthenolide also modifies cellular signaling pathways (PI3K/Akt, MAPK) that regulate chemotherapy drug sensitivity, potentially producing unpredictable interactions that could enhance or reduce anticancer drug efficacy.

Do not combine feverfew with chemotherapy without oncologist supervision. No clinical trials have established safety of this combination. The antiplatelet properties of feverfew additionally increase thrombocytopenic bleeding risk common in chemotherapy patients.

Feverfew is used for migraine prophylaxis (evidence grade B) via mechanisms that include serotonin inhibition, prostaglandin pathway suppression, and calcium channel modulation. Pharmacodynamic overlap with triptans (5-HT1B/1D agonists) may produce unpredictable vasomotor effects. Concurrent prophylactic and acute migraine medications require careful coordination to avoid serotonin syndrome risk.

If using both feverfew (prophylaxis) and triptans (acute treatment), coordinate with neurologist. Generally, the combination is considered manageable in clinical practice, but monitor for cardiovascular vasoconstrictive effects and signs of serotonin syndrome with co-administration.