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

B - reviewed clinical column, source pending

Matched on

“anticoagulant”

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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

“antidiabetic drugs”

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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

“antihypertensive”

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

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. 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. 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. 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

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