Foxglove ☠️

What Is Foxglove?

Foxglove is a tall European biennial with one-sided spikes of drooping, purple, bell-shaped flowers, and every part of it is poisonous. Its leaves contain cardiac glycosides, chiefly digitoxin and gitoxin, which act directly on the heart ^{14,16Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}.

Digitalis purpurea grows wild in western Europe and northern Morocco, on acid soils in woodland clearings, heaths and hedge banks ^{29,33Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 33Plants of the World Online (n.d.)Digitalis purpurea LView study →}. It is widely grown in gardens and has naturalised on several continents ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

The same glycosides that poison also treat heart failure. Foxglove leaf entered medicine through William Withering’s Account of the Foxglove (1785), and its glycosides are now purified and prescribed as measured doses under medical supervision ^{20,21Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →Reference 21Pagliaro L et al. · 2015Pagliaro L, Colli A, Bobbio M (2015). [Individual response to treatment: from Withering to contemporary medicine] — historical article. Recenti Prog Med 106(7):308-315. https://pubmed.ncbi.nlm.nih.gov/26228721/View study →}.

In its first year foxglove is a low rosette of soft grey-green leaves. At that stage it has been mistaken for comfrey, borage and sorrel, and eaten ^{15,16,26Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →}.

Identification & Lookalikes

Foxglove spends its first year as a flat basal rosette of softly downy, grey-green, conspicuously veined leaves with a scalloped edge, and no flower stalk ^{29,31Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 31NC State Extension (n.d.)Digitalis purpurea (common foxglove)View study →}. In the second year it sends up the familiar spike of purple bells ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}. Accidental poisonings have followed leaves picked before the plant flowered ^{26,27Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →Reference 27Lin CC et al. · 2010Case reportAn outbreak of foxglove leaf poisoning — case seriesView study →}.

Plant confused with it	How it differs
Comfrey (Symphytum officinale)	The best-documented confusion. In the published cases the leaves were picked as comfrey and brewed into a home-made tea 26,27,28Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →Reference 27Lin CC et al. · 2010Case reportAn outbreak of foxglove leaf poisoning — case seriesView study →Reference 28Vithayathil MK · 2016Case reportComfrey herbal remedy causing second-degree heart block: do not be outfoxed by digitalis — case reportView study →. Comfrey is itself a skin-only herb, never one to drink. Comfrey leaves are large, coarse and hairy, the bases of the upper leaves run down the stem, and the stems are winged 32Reference 32NC State Extension (n.d.)Symphytum officinale, Borago officinalis and Verbascum thapsusView study →. Foxglove leaves are softly downy 29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →
Borage (Borago officinalis)	Mistaken for foxglove in a home-made pie and in a dish of garden vegetables 16,17Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →Reference 17Iraci F et al. · 2023Case reportOf mixed vegetables and cardiac arrhythmias — foxglove poisoning case seriesView study →. Borage leaves are covered in bristly hairs, and the leaves and stems smell and taste of cucumber 32Reference 32NC State Extension (n.d.)Symphytum officinale, Borago officinalis and Verbascum thapsusView study →
Sorrel (Rumex acetosa)	Mistaken for foxglove in a wild-herb smoothie picked in woodland 15Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →
Mullein (Verbascum thapsus)	Also forms a first-year rosette of large grey-green, velvety leaves. Mullein’s leaves and stems are densely woolly, and its second-year spike carries yellow flowers 32Reference 32NC State Extension (n.d.)Symphytum officinale, Borago officinalis and Verbascum thapsusView study →

Taste and appearance give no guide to how much glycoside a leaf holds. Levels vary with the season and the place the plant grew, and with how the leaf is dried ^{14,15Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →}.

Botany

Foxglove is a biennial herb in the plantain family (Plantaginaceae) ^{31Reference 31NC State Extension (n.d.)Digitalis purpurea (common foxglove)View study →}. Older floras place it in Scrophulariaceae, where Flora of China still treats it ^{30Reference 30Hong D et al.Digitalis purpureaView study →}.

In its first year the plant forms a rosette of oblong to lance-shaped, softly hairy, grey-green leaves with rounded teeth along the edge ^{29,30Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 30Hong D et al.Digitalis purpureaView study →}. The basal leaves have a long, winged stalk, while the leaves on the flowering stem are stalkless ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}. The rosette stays green through the winter ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

In the second year a flowering stem grows from the centre of the rosette, usually 60–120 cm tall and occasionally up to 2 m ^{29,30Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 30Hong D et al.Digitalis purpureaView study →}. It carries around 60 drooping, bell-shaped flowers on one side of the stem, pale to deep pinkish-purple and sometimes white ^{29,30Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 30Hong D et al.Digitalis purpureaView study →}. Each flower is 3–5.5 cm long and spotted deep purple on a white, hairy ground inside ^{29,30Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 30Hong D et al.Digitalis purpureaView study →}. Bumblebees pollinate them, and the flowers can fertilise themselves if bees do not visit ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

The fruit is a capsule about 1.1–1.5 cm long holding around 1,000 tiny seeds, and an average plant produces about 85,000 seeds, shaken out by the wind ^{29,30Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 30Hong D et al.Digitalis purpureaView study →}. Foxglove flowers once and then dies. In poor sites it can take more than two years to reach flowering size, and a damaged plant sometimes survives to flower again ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

The related woolly foxglove, Digitalis lanata, is the species whose leaves contain digoxin and supply the drug ^{16Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}. The decorative foxgloves grown in gardens are mostly forms of D. purpurea itself ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

Distribution

Foxglove is native to western and south-western Europe and northern Morocco ^{29,33Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →Reference 33Plants of the World Online (n.d.)Digitalis purpurea LView study →}. Its native European range runs from Portugal, Spain and France through Britain, Ireland and Belgium to Germany and Czechia, and north to Norway and Sweden ^{33,34Reference 33Plants of the World Online (n.d.)Digitalis purpurea LView study →Reference 34Weeds of Australia · 2016Digitalis purpurea — fact sheetView study →}.

It grows mainly on dry or well-drained acid soils, particularly where the ground has been disturbed by woodland clearing, fire or grazing animals ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}. Typical habitats are open woodland, heathland, scrub margins, clearings, hedge banks, road verges and waste ground, and it also grows on cliffs and walls ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}. It is much rarer in limestone districts ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}. In Britain and Ireland it reaches about 885 m ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

Foxglove has been spread well beyond its native range as a garden and medicinal plant. It is now naturalised in parts of central and northern Europe, North and South America, southern Australia and New Zealand ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}, and in disturbed ground at low elevations in China ^{30Reference 30Hong D et al.Digitalis purpureaView study →}.

In some of these places it is a listed environmental weed. It has invaded moist and wet forest, riparian areas and rainforest in Victoria and Tasmania ^{34Reference 34Weeds of Australia · 2016Digitalis purpurea — fact sheetView study →}. Tasmania declared every seed-producing foxglove a pest under its Biosecurity Act 2019; sterile garden cultivars are exempt ^{35Reference 35Department of Natural Resources et al.Foxglove (Digitalis) — declared weeds indexView study →}. In New Zealand, where it was first recorded as naturalised in 1867, it is on the Department of Conservation’s 2024 list of environmental weeds ^{36Reference 36New Zealand Plant Conservation Network (Digitalis purpureaView study →}.

The species is abundant and not of conservation concern ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

Phytochemistry

Foxglove leaf is characterised by cardenolides, steroid glycosides carrying chains of sugars ^{12,13Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →Reference 13Ravi BG et al. · 2020High-resolution tandem mass spectrometry dataset reveals fragmentation patterns of cardiac glycosides in leaves of the foxglove plantsView study →}.

Digitoxin is the main glycoside of D. purpurea leaf, alongside gitoxin ^{14,16Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}. In one analysis, leaf dried at 60 °C held 0.379 mg/g digitoxin and 0.197 mg/g gitoxin, and leaf dried at room temperature held about a quarter as much digitoxin (0.090 mg/g) ^{14Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →}. The seed held none of either ^{14Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →}.

The glycosides are built on the aglycones digitoxigenin, gitoxigenin and gitaloxigenin, the last giving gitaloxin ^{13Reference 13Ravi BG et al. · 2020High-resolution tandem mass spectrometry dataset reveals fragmentation patterns of cardiac glycosides in leaves of the foxglove plantsView study →}. The sugar chains attached to them affect how the glycosides are absorbed and how long they last.

Digoxin is the leaf glycoside of D. lanata, the species that supplies the drug, and D. purpurea leaf generally does not contain it ^{16Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}. Laboratory digoxin tests cross-react with the other glycosides, so a raised “digoxin” reading is common in foxglove poisoning ^{15,16Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}.

Digitonin is a steroidal saponin, not a cardenolide, and has no action on the heart. The seed is especially rich in it, at 18.4 mg/g, against 0.11 mg/g in the leaf ^{14Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →}.

Glycoside levels vary greatly with the season and the place the plant grew ^{15Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →}. This is why the crude leaf cannot be dosed.

Constituent Summary

Amounts are for dried leaf unless stated.

Toxicology

Class of poison. Cardenolide (cardiac glycoside), an inhibitor of the sodium–potassium pump (Na⁺/K⁺-ATPase) ^{12Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →}.

Mechanism. Digitoxin and its relatives block the Na⁺/K⁺-ATPase, the pump every cell uses to keep sodium out ^{12Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →}. In heart muscle, sodium builds up inside the cell and calcium follows it, so each contraction is stronger. Past a narrow point the same calcium loading triggers abnormal beats, which is why poisoning shows itself as arrhythmia. The therapeutic effect and the toxic effect come from the same action.

Course. Poisoning begins in the gut, with nausea, vomiting and weakness ^{22,26,27Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →Reference 27Lin CC et al. · 2010Case reportAn outbreak of foxglove leaf poisoning — case seriesView study →}. Heart effects follow, and can take many forms: slow heart rate, heart block, ventricular tachycardia (including the bidirectional type) and ventricular fibrillation ^{16,17,24,26Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →Reference 17Iraci F et al. · 2023Case reportOf mixed vegetables and cardiac arrhythmias — foxglove poisoning case seriesView study →Reference 24Grimard C et al. · 2005Case reportBidirectional ventricular tachycardia resulting from digoxin toxicity — case reportView study →Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →}. Confusion and weakness also occur ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}. Yellow vision (xanthopsia) is rare but relatively specific to glycoside poisoning ^{23Reference 23Haruna Y et al. · 2020Case reportXanthopsia due to digoxin toxicity as a cause of traffic accidents — case reportView study →}.

Potassium. Because the poisoned pump is what moves potassium into cells, severe acute poisoning raises blood potassium ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}. Marked hyperkalaemia goes with severe poisoning and a poor outcome ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}. A woman who died after drinking foxglove leaf brewed as comfrey tea had a potassium of 7.6 mEq/L on arrival ^{26Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →}.

Potency. No reliable figure exists for plant material, because glycoside content varies with season, place and drying ^{14,15Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →}. Five leaves baked into a pie caused heart block ^{16Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}. Drying, storage and boiling do not destroy the toxicity, and all parts are poisonous, the seeds especially ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

Antidote. Digoxin-specific antibody fragments (Fab) bind the glycoside. They are associated with better survival in poisoning by the medicines ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}. The evidence in plant poisoning is scarcer, and Fab has failed in some foxglove cases ^{22,26,27Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →Reference 27Lin CC et al. · 2010Case reportAn outbreak of foxglove leaf poisoning — case seriesView study →}. Treatment also includes activated charcoal, correcting electrolyte disturbances and supportive care ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}. The old teaching that intravenous calcium is dangerous in glycoside poisoning rests on animal reports from the 1930s; a later cohort found no harm, though there is no reason to give it ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}.

Fatalities. Deaths are documented. A 55-year-old woman died of refractory ventricular arrhythmia after drinking foxglove leaf tea she believed was comfrey, despite Fab and heart–lung bypass ^{26Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →}. In an outbreak from the same mistake, nine people were poisoned and all recovered ^{27Reference 27Lin CC et al. · 2010Case reportAn outbreak of foxglove leaf poisoning — case seriesView study →}. Deliberate self-poisoning with foxglove also occurs ^{18Reference 18Torrents R et al. · 2023ReviewDeliberate Self-Poisoning with Plants in Southeastern France, a Poison Center 20-Year Report — reviewView study →}. Livestock can be poisoned by hay that contains foxglove ^{29Reference 29Botanical Society of Britain et al.Digitalis purpurea L., Foxglove — Fermanagh Species AccountsView study →}.

Traditional & Historical Use

Early Use and Withering’s Account (1785)

Foxglove appears in medical writing as early as 1250, among the remedies of the Physicians of Myddfai, a Welsh family of healers ^{20Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →}. It was used erratically until the eighteenth century ^{20Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →}.

The Birmingham physician William Withering published An Account of the Foxglove and Some of Its Medical Uses in 1785 ^{20Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →}. He reported the results of 163 patients with dropsy (water retention), including those it failed to help ^{21Reference 21Pagliaro L et al. · 2015Pagliaro L, Colli A, Bobbio M (2015). [Individual response to treatment: from Withering to contemporary medicine] — historical article. Recenti Prog Med 106(7):308-315. https://pubmed.ncbi.nlm.nih.gov/26228721/View study →}. He sorted them into those who responded and those who did not, and recognised the responders as people with heart failure ^{21Reference 21Pagliaro L et al. · 2015Pagliaro L, Colli A, Bobbio M (2015). [Individual response to treatment: from Withering to contemporary medicine] — historical article. Recenti Prog Med 106(7):308-315. https://pubmed.ncbi.nlm.nih.gov/26228721/View study →}.

The fluid loss Withering saw follows from a stronger heartbeat rather than from a direct action on the kidney.

Irish Folk Use and Child Deaths (19th Century)

In nineteenth-century Ireland, foxglove was known as luss-more, “the great herb”. A handful of fresh leaves was boiled in water and the liquid given to a sick child believed to be a fairy changeling, in order to drive the fairy out ^{37Reference 37Pickells W · 1851Case reportDeleterious practice of some of the Irish peasantry connected with the belief in fairies — [historical case report]View study →}. It was also given to children with epilepsy, who were thought to be fairy-struck ^{37Reference 37Pickells W · 1851Case reportDeleterious practice of some of the Irish peasantry connected with the belief in fairies — [historical case report]View study →}.

The practice killed children. William Pickells, a Cork physician, described a family in which two of three children given the herb died, and a local botanic-garden curator who knew of nearly a dozen fatal cases in his own neighbourhood ^{37Reference 37Pickells W · 1851Case reportDeleterious practice of some of the Irish peasantry connected with the belief in fairies — [historical case report]View study →}. In March 1851 a woman in Nenagh, County Tipperary, was convicted of causing the death of a girl of about six by giving her large doses of foxglove ^{37Reference 37Pickells W · 1851Case reportDeleterious practice of some of the Irish peasantry connected with the belief in fairies — [historical case report]View study →}.

Pharmacopoeial Use (Now Obsolete)

Dried foxglove leaf remained an official drug into the twentieth century. In Denmark the leaves of D. purpurea and D. lanata were tested for glycoside activity, and the standardised powder was made into tinctures, infusions and tablets ^{20Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →}. Foxglove tinctures were in the Danish pharmacopoeia by 1828, before the drug could be standardised ^{20Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →}.

Once the glycosides were isolated and their structures known, the purified compounds replaced the leaf ^{20Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →}. Foxglove has no place in modern herbal practice.

The Drugs Derived From It

Foxglove’s glycosides are prescription medicines for heart failure and for controlling the heart rate in atrial fibrillation. Digitoxin is the main glycoside of D. purpurea, and digoxin comes from D. lanata, the source of that drug ^{16Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}. Both are given at measured doses with blood-level monitoring, because the gap between a working dose and a toxic one is small.

The heart-failure evidence comes from two large randomised trials. Digitoxin lowered the combined risk of death or hospital admission for heart failure in DIGIT-HF, and digoxin reduced hospital admissions, without reducing deaths, in the DIG trial ^{1,2Reference 1Bavendiek U et al. · 2025RCTDigitoxin in Patients with Heart Failure and Reduced Ejection Fraction — randomised controlled trial (DIGIT-HF)View study →Reference 2Digitalis Investigation Group · 1997RCTThe effect of digoxin on mortality and morbidity in patients with heart failure — randomised controlled trial (DIG)View study →}. Anti-inflammatory, anticancer and antiviral uses are at an early stage ^{6,7,11Reference 6Zeitlin PL et al. · 2017RCTDigitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding — Phase II randomised controlled trialView study →Reference 7Mi C et al. · 2022In vitroDigitoxin promotes apoptosis and inhibits proliferation and migration by reducing HIF-1α and STAT3 in KRAS mutant human colon cancer cells — in vitroView study →Reference 11Škubník J et al. · 2021ReviewRepurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses — reviewView study →}.

Long-term digoxin use is linked to a higher incidence of breast and uterine cancer, through an estrogen-like effect ^{9,10Reference 9Biggar RJ et al. · 2011ObservationalDigoxin use and the risk of breast cancer in women — cohortView study →Reference 10Biggar RJ et al. · 2012ObservationalDigoxin use and the risk of cancers of the corpus uteri, ovary and cervix — cohortView study →}.

All of this evidence belongs to the purified glycosides at controlled doses. None of it was measured on the leaf.

Prescriptions for these drugs have fallen, but reports of digitoxin exposure to a German poison centre rose steadily from 1990 to 2023 ^{19Reference 19Ecker PAM et al. · 2026Critical analysis of digitalis glycosides: declining use but increasing poison-center exposure cases for digitoxinView study →}.

1. Cardiotonic (Heart Failure)

Cardiac glycosides increase the force of the heart’s contraction and slow conduction through the AV node, the basis of their use in heart failure and in rate control for atrial fibrillation.

The DIGIT-HF trial randomised 1,240 patients with heart failure and reduced ejection fraction to digitoxin, starting at 0.07 mg once daily, or placebo, on top of standard therapy ^{1Reference 1Bavendiek U et al. · 2025RCTDigitoxin in Patients with Heart Failure and Reduced Ejection Fraction — randomised controlled trial (DIGIT-HF)View study →}. Over a median 36 months, death from any cause or first hospital admission for worsening heart failure occurred in 39.5% on digitoxin and 44.1% on placebo (HR 0.82, 95% CI 0.69–0.98, P=0.03). Deaths alone did not differ significantly (HR 0.86, 95% CI 0.69–1.07) ^{1Reference 1Bavendiek U et al. · 2025RCTDigitoxin in Patients with Heart Failure and Reduced Ejection Fraction — randomised controlled trial (DIGIT-HF)View study →}.

The earlier DIG trial randomised 6,800 patients to digoxin (median 0.25 mg/day) or placebo. Mortality was unchanged (34.8% vs 35.1%), and fewer patients were admitted to hospital for worsening heart failure (26.8% vs 34.7%) ^{2Reference 2Digitalis Investigation Group · 1997RCTThe effect of digoxin on mortality and morbidity in patients with heart failure — randomised controlled trial (DIG)View study →}.

Meta-analyses of mostly observational data link digoxin with higher all-cause mortality: HR 1.21 across 326,426 patients, and 1.29 in atrial fibrillation ^{3,5Reference 3Vamos M et al. · 2015Meta-analysisDigoxin-associated mortality: a systematic review and meta-analysis of the literatureView study →Reference 5Vamos M et al. · 2019Meta-analysisMeta-Analysis of Effects of Digoxin on Survival in Patients with Atrial Fibrillation or Heart Failure: An UpdateView study →}. A review that separated study designs found the effect on mortality neutral in randomised trials, and attributed the excess in observational studies largely to sicker patients being given digoxin ^{4Reference 4Ziff OJ et al. · 2015Meta-analysisSafety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial dataView study →}.

Gap: the drugs improve symptoms and hospital admissions, and their effect on survival is neutral at best. No modern controlled trial has tested a whole-leaf preparation.

2. Anti-Inflammatory

Cardiac glycosides suppress NF-κB signalling, a driver of the neutrophil-rich airway inflammation of cystic fibrosis ^{11,12Reference 11Škubník J et al. · 2021ReviewRepurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses — reviewView study →Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →}.

A single-site, randomised, double-blind, placebo-controlled trial gave digitoxin at 0.05 or 0.1 mg daily, or placebo, to 24 adults with cystic fibrosis for 28 days ^{6Reference 6Zeitlin PL et al. · 2017RCTDigitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding — Phase II randomised controlled trialView study →}. The drug was safe at 0.1 mg daily. It did not significantly lower sputum IL-8 or neutrophil counts, the primary outcomes, although the higher dose reduced the expression of inflammatory genes in nasal cells ^{6Reference 6Zeitlin PL et al. · 2017RCTDigitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding — Phase II randomised controlled trialView study →}.

Gap: one small, 28-day trial of the isolated drug, which missed its primary outcome.

3. Anticancer

In KRAS-mutant colon-cancer cells, digitoxin promoted apoptosis and reduced proliferation and migration by lowering HIF-1α and STAT3 ^{7Reference 7Mi C et al. · 2022In vitroDigitoxin promotes apoptosis and inhibits proliferation and migration by reducing HIF-1α and STAT3 in KRAS mutant human colon cancer cells — in vitroView study →}. This fits a wider body of cell work on the Na⁺/K⁺-ATPase as a cancer target ^{12Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →}.

The human data point the other way. In Danish national registries, women currently taking digoxin had more breast cancer (RR 1.39) and uterine cancer (RR 1.48), and the breast-cancer risk returned to baseline once the drug was stopped ^{9,10Reference 9Biggar RJ et al. · 2011ObservationalDigoxin use and the risk of breast cancer in women — cohortView study →Reference 10Biggar RJ et al. · 2012ObservationalDigoxin use and the risk of cancers of the corpus uteri, ovary and cervix — cohortView study →}. A UK case-control study linked digoxin use to a modestly higher risk of pancreatic cancer (adjusted OR 1.41), with no effect on survival ^{8Reference 8Boursi B et al. · 2021ObservationalDigoxin use is associated with pancreatic cancer risk but does not affect survival — nested case-control cohortView study →}.

Gap: the anticancer signal is from cell lines only, while the human data show higher cancer risk with long-term use.

4. Antiviral

Many viruses depend on the host cell’s Na⁺/K⁺-ATPase and ion gradients to replicate, and cardiac glycosides inhibit a range of viruses in cell culture ^{11,12Reference 11Škubník J et al. · 2021ReviewRepurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses — reviewView study →Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →}. Reviews have proposed digitoxin and related cardenolides as candidate broad-spectrum antivirals ^{11Reference 11Škubník J et al. · 2021ReviewRepurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses — reviewView study →}.

Gap: the work is in cell culture and at the level of the compound class. There is no study of Digitalis purpurea itself and no human antiviral evidence.

Mechanisms

Foxglove’s cardenolides inhibit the Na⁺/K⁺-ATPase ^{12Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →}. In heart muscle this raises intracellular sodium and then calcium, which strengthens contraction and, at higher levels, triggers arrhythmia. The glycosides also slow conduction through the AV node.

The same pump inhibition has been studied for its effects on NF-κB signalling, on cancer-cell survival and on viral replication, almost entirely in cells ^{7,11,12Reference 7Mi C et al. · 2022In vitroDigitoxin promotes apoptosis and inhibits proliferation and migration by reducing HIF-1α and STAT3 in KRAS mutant human colon cancer cells — in vitroView study →Reference 11Škubník J et al. · 2021ReviewRepurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses — reviewView study →Reference 12Bejček J et al. · 2021ReviewNa⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — reviewView study →}.

Clinical Trials

Three completed human trials test the isolated glycosides: DIGIT-HF (digitoxin) and DIG (digoxin) in heart failure, and a Phase II digitoxin study in cystic fibrosis. No trial has tested a crude D. purpurea leaf preparation.

Last checked: August 2026.

Pharmaceutical Doses — Not Herbal Ones

These are the doses of the purified prescription drugs used in the trials, given under blood-level monitoring. There is no herbal dose of foxglove.

Indication	Preparation	Dose	Est. dried-herb equivalent	Source
Heart failure (reduced ejection fraction)	Isolated digitoxin (prescription drug)	0.07 mg once daily to start	Not derivable	1Reference 1Bavendiek U et al. · 2025RCTDigitoxin in Patients with Heart Failure and Reduced Ejection Fraction — randomised controlled trial (DIGIT-HF)View study →
Heart failure	Isolated digoxin (prescription drug)	median 0.25 mg/day	Not derivable	2Reference 2Digitalis Investigation Group · 1997RCTThe effect of digoxin on mortality and morbidity in patients with heart failure — randomised controlled trial (DIG)View study →
Cystic-fibrosis airway inflammation	Isolated digitoxin (Phase II)	0.05 or 0.1 mg/day for 28 days	Not derivable	6Reference 6Zeitlin PL et al. · 2017RCTDigitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding — Phase II randomised controlled trialView study →

No dried-leaf equivalent can be given, because leaf glycoside content varies too widely ^{14,15Reference 14Kwon HJ et al. · 2011HPLC method validation for Digitalis and its analogue by pulsed amperometric detectionView study →Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →}.

Historical Leaf Dose (Obsolete)

System	Preparation	Dose
Western medicine (historical, obsolete)	Powdered dried leaf, tincture or infusion	Adjusted to the individual patient’s response (Withering, 1785). Not used in modern practice 20,21Reference 20Norn S · 2004Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/View study →Reference 21Pagliaro L et al. · 2015Pagliaro L, Colli A, Bobbio M (2015). [Individual response to treatment: from Withering to contemporary medicine] — historical article. Recenti Prog Med 106(7):308-315. https://pubmed.ncbi.nlm.nih.gov/26228721/View study →

Safety & Pregnancy

Foxglove is poisonous in every part. Its glycosides have a narrow margin between a working dose and a lethal one, and the leaf’s content cannot be predicted.

Full Safety Detail

How poisoning shows itself. Glycoside poisoning begins with nausea, vomiting and weakness, and can bring confusion ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}. The dangerous features are in the heart: high blood potassium, a slow heart rate, heart block and ventricular arrhythmias that can be fatal ^{22,26Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →}. Yellow vision is rare but distinctive ^{23Reference 23Haruna Y et al. · 2020Case reportXanthopsia due to digoxin toxicity as a cause of traffic accidents — case reportView study →}. Digoxin-specific antibody fragments (Fab) are the antidote ^{22Reference 22Beaulieu J · 2024ReviewAntidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — reviewView study →}.

How people are poisoned. Foxglove has almost no herbal use, so poisoning comes from mistaking the leaves for something edible. Published cases include foxglove brewed as comfrey tea ^{26,27,28Reference 26Wu IL et al. · 2017Case reportFatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case reportView study →Reference 27Lin CC et al. · 2010Case reportAn outbreak of foxglove leaf poisoning — case seriesView study →Reference 28Vithayathil MK · 2016Case reportComfrey herbal remedy causing second-degree heart block: do not be outfoxed by digitalis — case reportView study →}, a spring wild-herb smoothie in which it was mistaken for sorrel ^{15Reference 15Kingma JS et al. · 2020Case reportKingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/View study →}, a pie made with five leaves sold by a garden nursery as borage ^{16Reference 16Negroni MS et al. · 2019Case reportA Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case reportView study →}, and a dish of garden vegetables that poisoned two women ^{17Reference 17Iraci F et al. · 2023Case reportOf mixed vegetables and cardiac arrhythmias — foxglove poisoning case seriesView study →}. Deliberate self-poisoning with the plant also occurs ^{18Reference 18Torrents R et al. · 2023ReviewDeliberate Self-Poisoning with Plants in Southeastern France, a Poison Center 20-Year Report — reviewView study →}. In nineteenth-century Ireland, children died after being given foxglove leaf as a folk remedy ^{37Reference 37Pickells W · 1851Case reportDeleterious practice of some of the Irish peasantry connected with the belief in fairies — [historical case report]View study →}. Garden foxglove is also a risk to children who eat its leaves or flowers, so keep it out of their reach.

Drug interactions. Digitoxin, the main glycoside of this species, is carried by the P-glycoprotein transporter in the same way as digoxin ^{38Reference 38Pauli-Magnus C et al. · 2001In vitroP-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin — in vitroView study →}. In people, drugs that block or induce this transporter change digoxin levels ^{25Reference 25Coumau C · 2025Systematic reviewA systematic review and classification of the effects of P-glycoprotein inhibitors and inducers in humans, using digoxin, fexofenadine, and dabigatran as probe drugs — systematic reviewView study →}.

Digitoxin is broken down mainly by the liver enzyme CYP3A ^{39Reference 39Eberhart DC et al. · 1991In vitroSpecies differences in the toxicity and cytochrome P450 IIIA-dependent metabolism of digitoxin — in vitro (human and animal liver microsomes)View study →}. In a patient taking digitoxin, adding rifampicin, which induces CYP3A, made blood digitoxin fall markedly until it was stopped ^{40Reference 40Poor DM et al. · 1983Case reportInteraction of rifampin and digitoxin — case reportView study →}. Potassium-losing diuretics add to toxicity by lowering blood potassium. These interactions are known for the purified drugs. No crude foxglove preparation is in legitimate use.

References

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2. Digitalis Investigation Group (1997). The effect of digoxin on mortality and morbidity in patients with heart failure — randomised controlled trial (DIG). N Engl J Med 336(8):525-533. https://pubmed.ncbi.nlm.nih.gov/9036306/
3. Vamos M, Erath JW, Hohnloser SH (2015). Digoxin-associated mortality: a systematic review and meta-analysis of the literature. Eur Heart J 36(28):1831-1838. https://pubmed.ncbi.nlm.nih.gov/25939649/
4. Ziff OJ, Lane DA, et al. (2015). Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ 351:h4451. https://pubmed.ncbi.nlm.nih.gov/26321114/
5. Vamos M, Erath JW, et al. (2019). Meta-Analysis of Effects of Digoxin on Survival in Patients with Atrial Fibrillation or Heart Failure: An Update. Am J Cardiol 123(1):69-74. https://pubmed.ncbi.nlm.nih.gov/30539748/
6. Zeitlin PL, Diener-West M, et al. (2017). Digitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding — Phase II randomised controlled trial. Ann Am Thorac Soc 14(2):220-229. https://pubmed.ncbi.nlm.nih.gov/28006108/
7. Mi C, Cao X, Ma K, et al. (2022). Digitoxin promotes apoptosis and inhibits proliferation and migration by reducing HIF-1α and STAT3 in KRAS mutant human colon cancer cells — in vitro. Chem Biol Interact 351:109729. https://pubmed.ncbi.nlm.nih.gov/34717917/
8. Boursi B, Huber JS, et al. (2021). Digoxin use is associated with pancreatic cancer risk but does not affect survival — nested case-control cohort. Cancer Causes Control 32(1):41-48. https://pubmed.ncbi.nlm.nih.gov/33064241/
9. Biggar RJ, Wohlfahrt J, Oudin A, et al. (2011). Digoxin use and the risk of breast cancer in women — cohort. J Clin Oncol 29(16):2165-2170. https://pubmed.ncbi.nlm.nih.gov/21422417/
10. Biggar RJ, Wohlfahrt J, Melbye M (2012). Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix — cohort. Int J Cancer 131(3):716-721. https://pubmed.ncbi.nlm.nih.gov/21913187/
11. Škubník J, Bejček J, et al. (2021). Repurposing Cardiac Glycosides: Drugs for Heart Failure Surmounting Viruses — review. Molecules 26(18):5627. https://pubmed.ncbi.nlm.nih.gov/34577097/
12. Bejček J, Spiwok V, et al. (2021). Na⁺/K⁺-ATPase Revisited: On Its Mechanism of Action, Role in Cancer, and Activity Modulation — review. Molecules 26(7):1905. https://pubmed.ncbi.nlm.nih.gov/33800655/
13. Ravi BG, Guardian MGE, et al. (2020). High-resolution tandem mass spectrometry dataset reveals fragmentation patterns of cardiac glycosides in leaves of the foxglove plants. Data Brief 30:105464. https://pubmed.ncbi.nlm.nih.gov/32300626/
14. Kwon HJ, Sim HJ, et al. (2011). HPLC method validation for Digitalis and its analogue by pulsed amperometric detection. J Pharm Biomed Anal 54(1):217-221. https://pubmed.ncbi.nlm.nih.gov/20800985/
15. Kingma JS, Frenay IM, et al. (2020). [A poisonous spring smoothie with wild herbs: accidental intoxication with foxglove (Digitalis purpurea)] — case report. Ned Tijdschr Geneeskd 164:D5306. https://pubmed.ncbi.nlm.nih.gov/33331728/
16. Negroni MS, Marengo A, et al. (2019). A Case Report of Accidental Intoxication following Ingestion of Foxglove Confused with Borage — case report. Case Rep Cardiol 2019:9707428. https://pubmed.ncbi.nlm.nih.gov/31871798/
17. Iraci F, Herdeg C, et al. (2023). Of mixed vegetables and cardiac arrhythmias — foxglove poisoning case series. J Cardiol Cases 28(2):86-90. https://pubmed.ncbi.nlm.nih.gov/37521578/
18. Torrents R, Reynoard J, et al. (2023). Deliberate Self-Poisoning with Plants in Southeastern France, a Poison Center 20-Year Report — review. Toxins (Basel) 15(12):671. https://pubmed.ncbi.nlm.nih.gov/38133175/
19. Ecker PAM, Schaper A, et al. (2026). Critical analysis of digitalis glycosides: declining use but increasing poison-center exposure cases for digitoxin. Eur J Clin Pharmacol 82(7):186. https://pubmed.ncbi.nlm.nih.gov/42334625/
20. Norn S, Kruse PR (2004). [Cardiac glycosides: From ancient history through Withering’s foxglove to endogenous cardiac glycosides] — historical article. Dan Medicinhist Arbog 32:119-132. https://pubmed.ncbi.nlm.nih.gov/15685783/
21. Pagliaro L, Colli A, Bobbio M (2015). [Individual response to treatment: from Withering to contemporary medicine] — historical article. Recenti Prog Med 106(7):308-315. https://pubmed.ncbi.nlm.nih.gov/26228721/
22. Beaulieu J, St-Onge M (2024). Antidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: a narrative review — review. Resusc Plus 19:100690. https://pubmed.ncbi.nlm.nih.gov/39006132/
23. Haruna Y, Kawasaki T, Kikkawa Y, Mizuno R, Matoba S (2020). Xanthopsia due to digoxin toxicity as a cause of traffic accidents — case report. Am J Case Rep 21:e924025. https://pubmed.ncbi.nlm.nih.gov/32769961/
24. Grimard C, De Labriolle A, Charbonnier B, Babuty D (2005). Bidirectional ventricular tachycardia resulting from digoxin toxicity — case report. J Cardiovasc Electrophysiol 16(7):807-808. https://pubmed.ncbi.nlm.nih.gov/16050845/
25. Coumau C, Csajka C (2025). A systematic review and classification of the effects of P-glycoprotein inhibitors and inducers in humans, using digoxin, fexofenadine, and dabigatran as probe drugs — systematic review. Clin Pharmacokinet 64(6):849-863. https://pubmed.ncbi.nlm.nih.gov/40349292/
26. Wu IL, Yu JH, Lin CC, Seak CJ, Olson KR, Chen HY (2017). Fatal cardiac glycoside poisoning due to mistaking foxglove for comfrey — case report. Clin Toxicol (Phila) 55(7):670-673. https://pubmed.ncbi.nlm.nih.gov/28463019/
27. Lin CC, Yang CC, Phua DH, Deng JF, Lu LH (2010). An outbreak of foxglove leaf poisoning — case series. J Chin Med Assoc 73(2):97-100. https://pubmed.ncbi.nlm.nih.gov/20171590/
28. Vithayathil MK, Edwards M (2016). Comfrey herbal remedy causing second-degree heart block: do not be outfoxed by digitalis — case report. BMJ Case Rep 2016:bcr2016216995. https://pubmed.ncbi.nlm.nih.gov/27908913/
29. Botanical Society of Britain and Ireland (n.d.). Digitalis purpurea L., Foxglove — Fermanagh Species Accounts. https://fermanagh.bsbi.org/digitalis-purpurea-l
30. Hong D, Yang H, Jin C, Fischer MA, Holmgren NH, Mill RR (n.d.). Digitalis purpurea. In: Flora of China, Vol. 18 (Scrophulariaceae). http://www.efloras.org/florataxon.aspx?flora_id=2&taxon_id=200020644
31. NC State Extension (n.d.). Digitalis purpurea (common foxglove). North Carolina Extension Gardener Plant Toolbox. https://plants.ces.ncsu.edu/plants/digitalis-purpurea/
32. NC State Extension (n.d.). Symphytum officinale, Borago officinalis and Verbascum thapsus. North Carolina Extension Gardener Plant Toolbox. https://plants.ces.ncsu.edu/plants/symphytum-officinale/ · https://plants.ces.ncsu.edu/plants/borago-officinalis/ · https://plants.ces.ncsu.edu/plants/verbascum-thapsus/
33. Plants of the World Online (n.d.). Digitalis purpurea L. Royal Botanic Gardens, Kew. https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:802077-1
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37. Pickells W (1851). Deleterious practice of some of the Irish peasantry connected with the belief in fairies — [historical case report]. Edinb Med Surg J, 76(188), 57-63. https://pubmed.ncbi.nlm.nih.gov/30332233/
38. Pauli-Magnus C, Mürdter T, Godel A, et al. (2001). P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin — in vitro. Naunyn Schmiedebergs Arch Pharmacol 363(3):337-343. https://pubmed.ncbi.nlm.nih.gov/11284449/
39. Eberhart DC, Gemzik B, Halvorson MR, et al. (1991). Species differences in the toxicity and cytochrome P450 IIIA-dependent metabolism of digitoxin — in vitro (human and animal liver microsomes). Mol Pharmacol 40(5):859-867. https://pubmed.ncbi.nlm.nih.gov/1944247/
40. Poor DM, Self TH, Davis HL (1983). Interaction of rifampin and digitoxin — case report. Arch Intern Med 143(3):599. https://pubmed.ncbi.nlm.nih.gov/6830398/

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