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

“anti-coagulants”

Find evidence for this pair Map this mechanism

Chemistry of this pair. Piperine inhibits CYP3A4, UGT and P-glycoprotein and increases intestinal permeability, raising the exposure of many co-administered drugs.

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

B - reviewed clinical column, source pending

Matched on

“anti-epileptics”

Find evidence for this pair Map this mechanism

Chemistry of this pair. Piperine inhibits CYP3A4, UGT and P-glycoprotein and increases intestinal permeability, raising the exposure of many co-administered drugs.

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

Chemistry of this pair. Piperine inhibits CYP3A4, UGT and P-glycoprotein and increases intestinal permeability, raising the exposure of many co-administered drugs.

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

D - in silico rule prediction only

Find evidence for this pair Map this mechanism

Chemistry of this pair. Volatile terpenes are lipophilic, cross membranes readily and induce or inhibit CYP2B6 and CYP3A4 depending on the constituent.

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