Chemistry of this pair. Isoflavone and lignan aglycones bind oestrogen receptor beta with measurable affinity and inhibit aromatase and sulfotransferase.

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

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Chemistry of this pair. Phenylpropanoids inhibit platelet aggregation and thromboxane synthesis and are direct mucosal irritants; some deplete hepatic glutathione at high dose.

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

D - in silico rule prediction only

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Chemistry of this pair. Phenylpropanoids inhibit platelet aggregation and thromboxane synthesis and are direct mucosal irritants; some deplete hepatic glutathione at high dose.

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

D - in silico rule prediction only

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Chemistry of this pair. Phenylpropanoids inhibit platelet aggregation and thromboxane synthesis and are direct mucosal irritants; some deplete hepatic glutathione at high dose.

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

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Chemistry of this pair. Isoflavone and lignan aglycones bind oestrogen receptor beta with measurable affinity and inhibit aromatase and sulfotransferase.

Class mechanism. CYP3A4-inducing botanicals accelerate ethinylestradiol and progestin clearance. Separately, isoflavone, lignan and coumestan phyto-oestrogens bind oestrogen receptors and may add to or compete with prescribed hormones.

Expected

Breakthrough bleeding and contraceptive failure; unpredictable effect in hormone-sensitive malignancy.

Management

Advise a second, non-hormonal contraceptive method. Avoid phyto-oestrogens in oestrogen-receptor-positive breast cancer without oncology advice.

Onset

delayed

Evidence

D - in silico rule prediction only

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Chemistry of this pair. Phenylpropanoids inhibit platelet aggregation and thromboxane synthesis and are direct mucosal irritants; some deplete hepatic glutathione at high dose.

Class mechanism. Salicylate-, coumarin- and eugenol-bearing botanicals add both antiplatelet activity and direct gastric mucosal irritation to cyclo-oxygenase inhibition; several also reduce renal prostaglandin-dependent perfusion.

Expected

Peptic ulceration, upper GI bleeding, acute kidney injury in volume-depleted patients.

Management

Avoid in ulcer history. Add gastroprotection where the combination is unavoidable, and monitor renal function in the elderly.

Onset

rapid

Evidence

D - in silico rule prediction only

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Chemistry of this pair. Isoflavone and lignan aglycones bind oestrogen receptor beta with measurable affinity and inhibit aromatase and sulfotransferase.

Class mechanism. Guggulsterone stimulates thyroid function and T4-to-T3 conversion; goitrogenic glucosinolates and lithospermic acid suppress it; high-fibre and cation-rich botanicals bind levothyroxine in the gut and reduce absorption.

Expected

Iatrogenic hyper- or hypothyroidism, unexplained TSH drift, loss of euthyroid control.

Management

Separate levothyroxine from fibre and mineral products by 4 hours. Recheck TSH 6-8 weeks after any botanical change.

Onset

unspecified

Evidence

D - in silico rule prediction only

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