Class mechanism. Hypericin- and hyperforin-type constituents inhibit monoamine reuptake and induce CYP3A4/2C19 and P-glycoprotein; others inhibit CYP2D6, raising tricyclic and SSRI concentrations.

Expected

Serotonin syndrome (agitation, clonus, hyperthermia, autonomic instability) or loss of antidepressant effect on withdrawal of an inducer.

Management

Screen for serotonergic burden before adding. Taper rather than stop abruptly. Consider therapeutic drug monitoring for tricyclics.

Onset

rapid

Evidence

B - reviewed clinical column, source pending

Matched on

“antidepressants”

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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

“antiepileptics”

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Class mechanism. Botanical mu-agonists and CNS depressants add to opioid respiratory and sedative effect; CYP2D6 and CYP3A4 modulation alters the conversion of codeine and tramadol to active metabolites.

Expected

Respiratory depression, over-sedation, constipation, ileus; unpredictable analgesia in CYP2D6 poor or ultrarapid metabolisers.

Management

Avoid concurrent botanical sedatives. Counsel on overdose signs and ensure naloxone availability where risk is high.

Onset

rapid

Evidence

B - reviewed clinical column, source pending

Matched on

“opioids”

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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

“sedative antihistamines”

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Class mechanism. Additive CNS depression plus shared hepatic injury pathways; alcohol also increases the extraction and absorption of lipophilic botanical constituents from tinctures.

Expected

Excess sedation, impaired judgement, higher risk of botanical hepatotoxicity.

Management

Advise abstinence with sedative or hepatotoxic botanicals; note the ethanol content of tinctures in recovering patients.

Onset

rapid

Evidence

B - reviewed clinical column, source pending

Matched on

“alcohol”

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Class mechanism. Sedating antihistamines add to botanical CNS depression, and their antimuscarinic component adds to tropane alkaloid burden.

Expected

Drowsiness, impaired coordination, dry mouth, urinary hesitancy, confusion in the elderly.

Management

Prefer non-sedating agents. Warn about driving during the first week of combined use.

Onset

rapid

Evidence

B - reviewed clinical column, source pending

Matched on

“antihistamines”

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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

“antihypertensives”

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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. 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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