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”

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Class mechanism. Hypoglycaemic botanicals act through insulin secretagogue, insulin-sensitising, alpha-glucosidase-inhibiting or glucose-transport routes. Added to a titrated pharmacological regimen the effects summate rather than plateau.

Expected

Symptomatic hypoglycaemia, sweating, tremor, confusion; severe events reported with insulin and sulfonylureas.

Management

Increase self-monitoring frequency for 2 weeks after starting or stopping. Anticipate a downward dose adjustment of insulin or sulfonylurea.

Onset

rapid

Evidence

B - reviewed clinical column, source pending

Matched on

“anti- diabetic”

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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

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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

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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

D - in silico rule prediction only

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Chemistry of this pair. Alkaloidal bases have pH-dependent absorption and commonly interact with hepatic CYP isoenzymes and efflux transporters.

Class mechanism. Gastric pH elevation alters the dissolution and ionisation of alkaloidal and enteric-coated botanical products; menthol- and peppermint-oil products lose their enteric protection at high pH and can be released prematurely.

Expected

Reduced or erratic absorption of alkaloids; heartburn and reflux from premature release of volatile-oil preparations.

Management

Separate administration by 2 hours. Avoid non-enteric peppermint oil in reflux disease.

Onset

unspecified

Evidence

D - in silico rule prediction only

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