Achillea millefolium · PhytoNexus

01 Identity and provenance

Accepted binomial: Achillea millefolium
Common names: Yarrow
Family (APG IV): Asteraceae
Part used: Herb
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): Reference not supplied - claim unverified against primary literature.

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Flavonoids, Sesquiterpene lactones, Volatile oils, Phenolic acids, Coumarins	Apigenin, Luteolin, Achillin, Chamazulene, Cineole, Borneol Herb	Celecoxib, Diclofenac, Ibuprofen, Drotaverine (anti-inflammatory/antispasmodic similarity); Warfarin analogues (coumarin scaffold—not therapeutic equivalence)

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: Wound healing, anti-inflammatory, dyspepsia, menstrual disorders, antispasmodic, antimicrobial
Marketed in: Herbal teas, tinctures, capsules, wound creams, ointments, essential oils
Reported adverse effects: Allergic dermatitis (Asteraceae allergy), photosensitivity, gastrointestinal discomfort, increased bleeding risk (theoretical)

04 Interaction matrix

Source column, verbatim: Anticoagulants, antiplatelets, antihypertensives, sedatives, CYP3A4 substrates (possible), diuretics
Normalised onto 6 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Narrow-therapeutic-index CYP3A4 substrates Pharmacokinetic	4Contraindicated	PK-CYP3A4	curated B	Toxic accumulation or subtherapeutic failure of the co-prescribed drug, s…	why ▾
Chemistry of this pair. Coumarin and furanocoumarin nuclei interfere with vitamin-K-dependent clotting-factor synthesis and inhibit CYP3A4 and CYP2C9 at the intestinal wall. Class mechanism. Furanocoumarins, bergamottin, piperine, glabridin and berberine inhibit CYP3A4; hyperforin, andrographolide and several diterpenes induce it through PXR. Because CYP3A4 handles roughly half of marketed drugs, the affected list is broad and the direction is product-specific. Expected Toxic accumulation or subtherapeutic failure of the co-prescribed drug, sometimes fatal for antiarrhythmics, immunosuppressants and oncology agents. Management Screen the full regimen for 3A4 substrates. Where the substrate has a narrow index, avoid rather than monitor. Onset unspecified Evidence B - reviewed clinical column, source pending Matched on “cyp3a4 substrates” Find evidence for this pair Map this mechanism
Anticoagulants (vitamin-K antagonists, DOACs) Haemostasis	3Major	PD-additive + PK-CYP2C9	curated B	INR destabilisation in either direction; ecchymosis, epistaxis, gum bleed…	why ▾
Chemistry of this pair. Coumarin and furanocoumarin nuclei interfere with vitamin-K-dependent clotting-factor synthesis and inhibit CYP3A4 and CYP2C9 at the intestinal wall. Class mechanism. Coumarin-, salicylate- and coumestan-bearing botanicals add to vitamin-K-antagonist effect; several also compete for CYP2C9 and CYP3A4, raising S-warfarin exposure. Botanicals rich in vitamin K1 act in the opposite direction and blunt anticoagulation. Expected INR destabilisation in either direction; ecchymosis, epistaxis, gum bleeding, GI or intracranial haemorrhage. Management Do not start or stop the botanical without INR cover. Check INR at 3-5 days and again at 2 weeks. Document the product, batch and dose in the anticoagulation record. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “anticoagulants” Find evidence for this pair Map this mechanism
Antiplatelet agents Haemostasis	3Major	PD-additive	curated B	Prolonged bleeding time, surgical and post-procedural bleeding, bruising,…	why ▾
Chemistry of this pair. Flavonoids inhibit CYP3A4, CYP1A2, OATP1B1 and UGT to a variable extent and have measurable antiplatelet activity. Class mechanism. Organosulfur compounds, gingerols, salicylates, ginkgolides and eugenol inhibit thromboxane A2 synthesis, platelet aggregation and PAF-mediated activation, duplicating the pharmacology of aspirin and P2Y12 blockers. Expected Prolonged bleeding time, surgical and post-procedural bleeding, bruising, haematuria. Management Stop the botanical 7-14 days before elective surgery or neuraxial anaesthesia. Record it on the pre-operative medicines list. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “antiplatelets” Find evidence for this pair Map this mechanism
Diuretics Renal	3Major	PD-additive + electrolyte-mediated	curated B	Hypokalaemia, hyponatraemia, dehydration, muscle weakness, cramps, arrhyt…	why ▾
Class mechanism. Aquaretic and saluretic botanicals add to renal potassium and sodium loss. Anthraquinone laxatives compound this through colonic potassium loss, and glycyrrhizin causes mineralocorticoid-like retention of sodium with kaliuresis. Expected Hypokalaemia, hyponatraemia, dehydration, muscle weakness, cramps, arrhythmia; potentiation of digoxin toxicity through low potassium. Management Check potassium, sodium and creatinine 1-2 weeks after starting. Avoid the combination entirely in patients also on digoxin. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “diuretics” Find evidence for this pair Map this mechanism
Sedatives, hypnotics and benzodiazepines CNS	3Major	PD-additive	curated B	Excess sedation, psychomotor and driving impairment, falls, respiratory d…	why ▾
Class mechanism. Valepotriate, kavalactone, apigenin, sesquiterpene and alkaloid constituents act at GABA-A, adenosine and histamine sites, summating with prescribed CNS depression. Some also inhibit CYP3A4 and raise benzodiazepine exposure. Expected Excess sedation, psychomotor and driving impairment, falls, respiratory depression when combined with opioids. Management Warn against driving and machine operation. Avoid triple combinations with opioids. Reduce hypnotic dose in older adults. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “sedatives” Find evidence for this pair Map this mechanism
Antihypertensives Cardiovascular	2Moderate	PD-additive	curated B	Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-p…	why ▾
Class mechanism. Vasodilator, diuretic, ACE-inhibitory and calcium-antagonist activity in botanical extracts adds to prescribed blood-pressure lowering. A minority (ephedrine-, glycyrrhizin- and caffeine-bearing) act in the opposite direction and antagonise control. Expected Orthostatic hypotension, dizziness, syncope and falls; or loss of blood-pressure control with pressor botanicals. Management Home BP log for 2 weeks after any change. Warn about postural symptoms; review in the elderly and in those on multiple agents. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “antihypertensives” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Cytotoxic and targeted anticancer drugs Oncology	4Contraindicated	PK-CYP3A4/UGT + PD-antagonistic	predicted D	Neutropenic sepsis and severe diarrhoea from over-exposure, or reduced an…	why ▾
Chemistry of this pair. Flavonoids inhibit CYP3A4, CYP1A2, OATP1B1 and UGT to a variable extent and have measurable antiplatelet activity. Class mechanism. Botanical CYP3A4 and UGT1A1 modulation alters exposure to irinotecan, taxanes, vinca alkaloids and kinase inhibitors. High-dose antioxidant botanicals may also oppose the oxidative mechanism of some cytotoxics and of proteasome inhibitors. Expected Neutropenic sepsis and severe diarrhoea from over-exposure, or reduced antitumour effect; boronic-acid proteasome inhibitors are directly antagonised by polyphenols. Management No botanical should be taken during active cytotoxic therapy without oncology sign-off. Record all supplements in the chemotherapy chart. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Antiepileptics CNS	3Major	PK-CYP induction + PD-antagonistic	predicted D	Breakthrough seizures, status epilepticus, or additive sedation and ataxi…	why ▾
Chemistry of this pair. Volatile monoterpenes are GABA-A antagonists at higher exposure, lowering seizure threshold, and are metabolised to reactive intermediates. Class mechanism. Enzyme-inducing botanicals lower plasma anticonvulsant concentrations, while GABAergic constituents add sedation and a few (thujone, camphor, beta-asarone, pinene-rich oils) are directly proconvulsant and lower seizure threshold. Expected Breakthrough seizures, status epilepticus, or additive sedation and ataxia. Management Measure anticonvulsant levels before and 2-4 weeks after any change. Avoid proconvulsant essential oils entirely in epilepsy. Onset delayed Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Hepatotoxic drugs Organ toxicity	3Major	Organ-toxicity additive	predicted D	Transaminase elevation, cholestasis, sinusoidal obstruction syndrome, acu…	why ▾
Chemistry of this pair. Volatile monoterpenes are GABA-A antagonists at higher exposure, lowering seizure threshold, and are metabolised to reactive intermediates. Class mechanism. Pyrrolizidine alkaloids, high-dose anthraquinones, kava constituents and germander-type diterpenes cause hepatocellular or sinusoidal injury that adds to the risk from paracetamol, isoniazid, methotrexate, azoles and statins. Expected Transaminase elevation, cholestasis, sinusoidal obstruction syndrome, acute liver failure. Management Baseline and 4-weekly ALT and bilirubin. Stop the botanical at any transaminase rise above three times the upper reference limit. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Statins and lipid-lowering drugs Cardiovascular	3Major	PK-CYP3A4/OATP	predicted D	Myalgia, raised creatine kinase, rhabdomyolysis, hepatic transaminase ele…	why ▾
Chemistry of this pair. Coumarin and furanocoumarin nuclei interfere with vitamin-K-dependent clotting-factor synthesis and inhibit CYP3A4 and CYP2C9 at the intestinal wall. Class mechanism. CYP3A4 and OATP1B1 inhibition by furanocoumarin- and flavonoid-rich botanicals raises simvastatin, atorvastatin and lovastatin exposure. Some botanicals themselves contain monacolin K, which is chemically lovastatin. Expected Myalgia, raised creatine kinase, rhabdomyolysis, hepatic transaminase elevation. Management Ask specifically about red-yeast-rice type products. Check CK and ALT if muscle symptoms appear; prefer a non-3A4 statin. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Topical antiseptics, keratolytics and irritants Dermatology	3Major	PD-additive local	predicted D	Contact dermatitis, chemical burn, photoirritation, unexpected systemic a…	why ▾
Chemistry of this pair. Volatile monoterpenes are GABA-A antagonists at higher exposure, lowering seizure threshold, and are metabolised to reactive intermediates. Class mechanism. Essential-oil terpenes, capsaicinoids and phorbol-type diterpenes add to the barrier disruption caused by topical antiseptics, retinoids and keratolytics, and increase percutaneous absorption of anything applied with them. Expected Contact dermatitis, chemical burn, photoirritation, unexpected systemic absorption from broken skin. Management Patch test first. Never apply undiluted essential oils to broken or freshly shaved skin, or with occlusion. Onset rapid Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Hypersensitivity and allergy risk Immunology	2Moderate	Immunological	predicted D	Urticaria, angio-oedema, allergic contact dermatitis, anaphylaxis; cross-…	why ▾
Chemistry of this pair. Alpha-methylene-gamma-lactone groups alkylate cysteine residues on NF-kB and are the principal Compositae contact allergens. Class mechanism. Sesquiterpene lactones, urushiol-type catechols and protein allergens cause type I and type IV reactions with well-documented cross-reactivity across the Asteraceae and Apiaceae. Expected Urticaria, angio-oedema, allergic contact dermatitis, anaphylaxis; cross-reaction with related species. Management Take an allergy history by plant family, not by product name. Withhold in known Compositae sensitivity. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

The audit recorded no hazard beyond the interaction profile. The controlled-vocabulary field reads not assessed, which means the assessment has not been done rather than that it came back clear.

06 Confusable material

No same-genus or shared-common-name entry in the corpus.

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Ruta graveolens Rue	Rutaceae	7	0.54
Centella asiatica Mandukaparni	Apiaceae	7	0.50
Ginkgo biloba Ginkgo	Ginkgoaceae	7	0.54
Artemisia absinthium Wormwood	Asteraceae	7	0.58
Actaea racemosa Black Cohosh	Ranunculaceae	7	0.54
Cyperus rotundus Nagarmotha	Cyperaceae	7	0.50

10 References and notes

No citation is on record for this entry. That is itself the finding: the audit flagged it, and it is why the entry does not carry an A evidence grade.

Curator notes

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