Gaultheria fragrantissima

01 Identity and provenance

Accepted binomial: Gaultheria fragrantissima
Common names: Wintergreen
Family (APG IV): Ericaceae
Part used: Leaf
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): 21 CFR 201.303 | PubMed 11335011 (laryngeal oedema, 4 mL fatal in a child) | Merck Manual, aspirin poisoning | VERIFIED 2026 (batch 6) - synthetic analogue, application, interactions, side effects and references populated from retrieved primary/regulatory sources. Interactions labelled CLINICAL vs THEORETICAL. Marketed-formulation column intentionally blank. | DOSE

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Phenolic ester	Methyl salicylate Leaf	Aspirin and salicylic acid - methyl salicylate is hydrolysed to salicylate after absorption. This is a TRUE structural relationship and the reason it is so dangerous.

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: Topical counter-irritant, rubefacient and analgesic in liniments, balms and Ayurvedic/Asian pain preparations; flavouring at minute concentrations.
Reported adverse effects: THE HIGHEST DOSE-DENSITY ENTRY IN THIS DATABASE. Oil of wintergreen is about 98% methyl salicylate: 1 mL equals roughly 1,400 mg of aspirin, and one teaspoon (5 mL) equals about 7,000 mg - some 22 adult aspirin tablets. A TEASPOON OR LESS HAS CAUSED WELL-DOCUMENTED DEATHS IN CHILDREN UNDER SIX; as little as 4 mL may be fatal in a child. The pleasant smell attracts children. Death has also been reported from excessive TOPICAL use (a 17-year-old runner). Salicylate toxidrome: tinnitus, hyperpnoea, vomiting, metabolic acidosis with respiratory alkalosis, lethargy, seizures. US FDA requires warning labelling on any drug product above 5% methyl salicylate (21 CFR 201.303).

04 Interaction matrix

Source column, verbatim: CLINICAL: additive with aspirin, other salicylates and NSAIDs; potentiates warfarin. Absorption is enhanced by broken or diseased skin, occlusive dressings, large application areas, heat and exercise - a psoriasis patient reached a salicylate level of 48.5 mg/dL from a topical herbal cream.
Normalised onto 2 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Anticoagulants (vitamin-K antagonists, DOACs) Haemostasis	4Contraindicated	PD-additive + PK-CYP2C9	curated A	INR destabilisation in either direction; ecchymosis, epistaxis, gum bleed…	why ▾
Chemistry of this pair. Salicylate esters hydrolyse to salicylic acid, giving irreversible platelet COX-1 acetylation equivalent to low-dose aspirin. 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 A - human data with a cited source Matched on “other salicylates” Find evidence for this pair Map this mechanism
NSAIDs Analgesia	4Contraindicated	PD-additive	curated A	Peptic ulceration, upper GI bleeding, acute kidney injury in volume-deple…	why ▾
Chemistry of this pair. Salicylate esters hydrolyse to salicylic acid, giving irreversible platelet COX-1 acetylation equivalent to low-dose aspirin. 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 A - human data with a cited source Matched on “aspirin” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antiplatelet agents Haemostasis	4Contraindicated	PD-additive	predicted D	Prolonged bleeding time, surgical and post-procedural bleeding, bruising,…	why ▾
Chemistry of this pair. Salicylate esters hydrolyse to salicylic acid, giving irreversible platelet COX-1 acetylation equivalent to low-dose aspirin. 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 Find evidence for this pair Map this mechanism

05 Hazard register

threshold - One teaspoon of oil of wintergreen = ~7,000 mg aspir

06 Confusable material

No same-genus or shared-common-name entry in the corpus.

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Myristica fragrans Nutmeg	Myristicaceae	3	0.43
Trachyspermum ammi Ajwain	Apiaceae	3	0.75
Kaempferia galanga Chandramula	Zingiberaceae	3	0.75
Alpinia galanga Greater Galangal	Zingiberaceae	3	0.75
Salix alba White Willow	Salicaceae	3	1.00
Filipendula ulmaria Meadowsweet	Rosaceae	3	1.00

10 References and notes

Source column: Davis JE. J Emerg Med 2007;32:63-9 (methyl salicylate exposure in toddlers). PubMed 17239735

Davis JE. J Emerg Med 2007

Davis JE 2007 manual

32:63-9 (methyl salicylate exposure in toddlers). PubMed 17239735

manual

BibTeX for all 2 records

@article{DavisJE2007,
  title = {Davis JE. J Emerg Med 2007},
  author = {Davis JE},
  year = {2007},
}

@article{anon,
  title = {32:63-9 (methyl salicylate exposure in toddlers). PubMed 17239735},
}

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