Digoxin

Brand Names: Lanoxin

Clinical Names: Digoxin

Summary

trade name: Digoxin

trade name: Lanoxin®

type of drug: Cardiac glycoside.

used to treat: Congestive heart failure and the associated symptoms of shortness of breath when lying flat, wheezing, and ankle swelling; certain cardiac arrhythmias, usually to slow heart rate in rapid atrial rhythm disturbances such as atrial fibrillation and atrial flutter.

overview of interactions:
• nutrient affecting drug performance: Aluminum-containing Antacids

• nutrient affecting drug toxicity: Calcium

• nutrient affected by drug: Magnesium

• nutrient affected by drug: Potassium

• nutrients affecting drug performance: Plantago psyllium (Psyllium seed husks), Cyamopsis species seeds (Guar gum) and potentially other sources of Dietary Fiber

• herb affecting drug toxicity: Crataegus species leaves/flowers/fruit (Hawthorn)

• herb affecting drug toxicity: Cytisus scoparius (Scotch Broom, flowering tops)

• herbs affecting drug toxicity: Digitalis (Foxglove) and other plants containing cardiac glycosides

• herb possibly affecting drug pharmacokinetics: Eleutherococcus senticosus (Siberian Ginseng)

• herb affecting drug toxicity: Glycyrrhiza glabra (Licorice Root)

• herb affecting drug toxicity: Hypericum perforatum (St. John's Wort)

• herbs affecting drug toxicity: Potassium-depleting Herbs, including laxatives and diuretics

• herbal concerns: Hypotensive and Bradycardic Herbs



Interactions

nutrient affecting drug performance: Aluminum-containing Antacids

• mechanism: Aluminum-containing antacids reduce the bioavailability of digoxin.
(Rodin SM, Johnson BF. Clin Pharmacokinet. 1988 Oct;15(4):227-244; Roe DA. 84, 1989; Gugler R, Allgayer H. Clin Pharmacokinet. 1990 Mar;18(3):210-219.)

• nutritional concerns: Individuals taking digoxin should avoid the use of antacids, especially within two hours of taking the medication.

nutrient affecting drug toxicity: Calcium

• mechanism: Small increases in plasma calcium can increase digoxin toxicity. Digoxin also increases renal clearance.
(Kupfer S, Kosovsky JD. J Clin Invest 1965 44:1132-1143.)

• nutritional concerns: Avoid high calcium foods for two hours before and after taking digoxin. Even under a physician's care intravenous calcium can be very dangerous.

nutrients affected by drug: Magnesium

• mechanism: Digoxin decreases intracellular magnesium, thereby causing increased urinary magnesium loss. Magnesium deficiencies induced by concomitant diuretic use are very common in individuals using digoxin. Hypomagnesemia may predispose to digitalis toxicity.
(Toffaletti J. Analyt Chem 1991 63(12):192R-194R; al-Ghamdi SM, et al. Am J Kidney Dis 1994 Nov;24(5):737-752.)

• clinical implications: Hypomagnesemia is known to produce a wide variety of clinical presentations, including neuromuscular irritability, cardiac arrhythmias, and increased sensitivity to digoxin. Magnesium deficiency also inhibits the therapeutic efficacy of digoxin in controlling atrial fibrillation. Refractory hypokalemia and hypocalcemia can be caused by concomitant hypomagnesemia and can be corrected with magnesium therapy.
(Toffaletti J. Analyt Chem 1991 63(12):192R-194R; Young IS, et al. Br J Clin Pharmacol. 1991 Dec;32(6):717-721; Lewis R, et al. Br J Clin Pharmacol. 1991 Feb;31(2):200-203.)

• testing: Many physicians are aware of the need to monitor and prescribe for potassium depletion but do not consider the issue of magnesium deficiency unless serum levels fall below acceptable levels. Furthermore, many physicians experienced in nutritional assessment consider serum magnesium to be a very poor indicator of how much magnesium is actually in the tissues. Serum magnesium concentration is maintained within a narrow range by the kidney and small intestine since under conditions of magnesium deprivation both organs increase their fractional absorption of magnesium. If magnesium depletion continues, the bone store contributes by exchanging part of its content with extracellular fluid (ECF). The serum Mg can be normal in the presence of intracellular Mg depletion, and the occurrence of a low level usually indicates significant magnesium deficiency. Hypomagnesemia is frequently encountered in hospitalized patients and is seen most often in patients admitted to intensive care units. The detection of magnesium deficiency can be increased by measuring magnesium concentration in the urine or using the parenteral magnesium load test.
(al-Ghamdi SM, et al. Am J Kidney Dis 1994 Nov;24(5):737-752; Marz R. 1997.)

• nutritional support: Individuals taking digoxin will almost always benefit from supplementation of magnesium. Studies and clinical experience indicate that 300-500 mg of magnesium per day would be an appropriate dosage level for supplementing such patients. Anyone taking digoxin should consult the prescribing physician and/or a nutritionally-oriented healthcare professional regarding the issue of magnesium supplementation.
(Kinlay S, Buckley NA. J Toxicol Clin Toxicol 1995;33(1):55-59; Sueta CA, et al. Magnes Res 1995 Dec;8(4):389-401.)

nutrients affected by drug: Potassium

• mechanism: Potassium deficiency induced by concomitant diuretic use are very common in individuals using digoxin, often being secondary to hypomagnesia. Hypokalemia may predispose to digitalis toxicity.

• nutritional support: Individuals taking digoxin will often benefit from increasing their intake of potassium. Many physicians who prescribe digoxin monitor for potassium depletion and prescribe potassium supplements when measurable deficiencies are found. However direct supplementation of potassium may not be appropriate since potassium pills are limited to dosages of 99 mg each and taking several at a time may cause digestive irritation. Adequate dietary potassium can easily be obtained by eating several pieces of fruit each day; for example, one banana typically provides 500 mg. Other research, including that by Schmidt et al, indicates that the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by exercise. Anyone taking digoxin should consult the prescribing physician and/or a nutritionally-oriented healthcare professional regarding the issue of potassium supplementation.
(Schmidt TA, et al. Cardiovasc Res 1995 Apr;29(4):506-511.)

nutrient affecting drug performance: Plantago psyllium (Psyllium seed husks), Cyamopsis spp. seeds (Guar gum) and potentially other sources of Dietary Fiber

• mechanism: Hydrophilic fiber slows absorption of oral drugs and specifically reduces absorption of digoxin.

• nutritional concern: Most studies thus far have indicated that the clinical implications of this reduced absorption may be negligent.
(Huupponen R, et al. Eur J Clin Pharmacol 1984;26(2):279-281; Johnson BF, et al. J Clin Pharmacol 1987 Jul;27(7):487-490.)

herb affecting drug toxicity: Crataegus species leaves/flowers/fruit (Hawthorn)

• mechanism: Hawthorn is a mild cardiotonic herb. It has moderate positive inotropic effects and can thus potentiate cardiac glycosides including digoxin. Hawthorn is used in herbal therapeutics as an adjunctive in reducing the dose and amounts of cardioactive pharmaceuticals used by patients with heart conditions.

• herbal concern: Hawthorn should not be used concurrently with any cardiovascular medication without consulting a physician or qualified herbalist. Patients on existing digoxin therapy should be monitored while taking Hawthorn and the digoxin dose adjusted as necessary.

herb affecting drug toxicity: Cytisus scoparius (Scotch Broom, flowering tops)

• mechanism: Scotch broom contains cardioactive alkylamines including sparteine. The herb has anti-arryhthmic and cardiodepressant activity and is diuretic and cathartic. It is hypertensive due to peripheral vasoconstrictive effects. Cytisus is used therapeutically by healthcare professionals trained in herbal medicine in combination with Convallaria for treatment of cardiac edema in congestive heart failure.
(British Herbal Pharmacopeia, 1983.)

• herbal concern: Cytisus may interact with digoxin and related drugs unpredictably due to multiple cardiac and circulatory effects. It should not be used concurrently with digoxin therapy.

herbs affecting drug toxicity: Digitalis (Foxglove) and other plants containing cardiac glycosides.

• mechanism: Naturally occurring cardiac glycosides have a limited distribution confined to a few dozen species scattered across several genera, principally the Asclepiadaceae and Apocyanaceae. Concentrations of glycosides are generally well below 1%. Three genera contain sufficient concentrations of glycosides for commercial extraction: Digitalis spp.- Foxgloves - (Scrophulariaceae), Urginia spp. - Squills - (Liliaceae) and Strophanthus (Apocynaceae). These plants are described as cardioactive by herbalists, as opposed to the milder cardiotonic herbs such as Hawthorn. Due to their toxicity, these herbs are not available to the public. Neither Digitalis or Strophanthus are commonly used in herbal therapeutics and in many countries their use is legally restricted. Convallaria majalis and Urginia maritima are listed in the British Herbal Pharmacopoeia. Their cardenolides have low cumulative toxicity compared to Digitalis, and these plants are used by professional herbalists. See Weiss (1988) for an excellent discussion of use of cardiac glycoside herbs.

Contamination of commercial crude herb with Digitalis has been reported. Recently, the FDA recalling several products after herb teas containing Plantain caused side effects attributable to Digitalis contamination. One study analyzed several herbal teas and found digitalis like factors present in small concentrations in several samples, particularly those containing Asclepias tuberosa (Pleurisy Root).
(Longerich L, et al. Clin Invest Med 1993 Jun;16(3):210-218.)

Intoxications due to inadvertent consumption of cardenolide containing plants from horticultural or wild settings are not uncommon, especially with Oleander; however, it is rarely serious.
The following plants contain cardiac glycosides, although some in very small (less than 0.1%) amounts).

Common herbs containing cardiac glycosides:
• Asclepias tuberosa (Pleurisy Root )*
• Convallaria majalis (Lily of the Valley)
• Scrophularia nodosa (Figwort) *
• Urginea maritima (Squill bulb)
Note: * These herbs contain therapeutically insignificant quantities of glycosides.

Restricted or unusual herbs containing cardiac glycosides:
• Adonis vernalis (Pheasant’s Eye)
• Apocynum cannabinum (Canadian Hemp Root) toxic
• Digitalis species (Foxglove) toxic
• Helleborus niger (Black Hellebore) toxic
• Helleborus viride (Christmas Rose) toxic
• Nerium oleander (Rose Laurel) toxic
• Strophanthus spp. (Ouabain, Kombe) toxic
• Thevetia neriifolia (Yellow Oleander) toxic

• mechanism: By their additive effects, cardiac glycosides from these plants can produce cardiac toxicity when used with digitalis glycosides such as digoxin or digitoxin or similar medicines. They should never be taken by anyone without the supervision of a physician or qualified herbalist experienced in their use, and they should never be combined with digoxin.

herb possibly affecting drug pharmacokinetics: Eleutherococcus senticosus (Siberian Ginseng)

• report: A case of elevated serum digoxin level in a patient taking Siberian ginseng and digoxin was reported by McRae. The mechanism of interaction remains unclear and since the ECG was unchanged, it is possible that the herb interfered with the digoxin assay.
(McRae S. CMAJ 1996 Aug 1;155(3):293-295, Comment in: CMAJ 1996 Nov 1;155(9):1237.)

• herbal concern: Individuals taking digoxin should advise their prescribing physician before commencing Siberian ginseng consumption to ensure adequate monitoring of both plasma drug levels and cardiac signs.

herb affecting drug toxicity: Glycyrrhiza glabra (Licorice Root)

• mechanism: Licorice root contains the triterpenoid glycyrrhizin which inhibits the metabolic degradation of mineralocorticoids and glucocorticoids, increasing their plasma levels. This leads to renal retention of sodium and water at the expense of potassium, causing hypertension, edema and weight gain, an effect described as "pseudoaldosteronism." In herbal therapeutics Licorice root is considered to be contraindicated for obese and hypertensive patients, and may lead to hypertension in normotensive patients. Excessive use of Licorice root can result in hypokalemia, or exacerbate a pre-existing hypokalemia and is therefore contraindicated in patients on cardioactive drugs, particularly cardiac glycosides. A product known as DGL (Deglycyrrhizinated Licorice) is available which retains the anti inflammatory and anti-ulcer actions of whole licorice root without pseudo-aldosterone side effects.

• herbal concerns: Many products, ranging from candy to laxatives and chewing tobacco contain concentrated licorice extracts in unstated quantities. All medical reports of licorice toxicity have been due to excessive consumption of such products rather than medicinal use of whole licorice root in the therapeutic dose range.

herb affecting drug toxicity: Hypericum perforatum (St. John's Wort)

• research: Johne et al conducted a preclinical trial which showed that coadministration of Hypericum extracts with digoxin resulted in decreased plasma digoxin levels compared to placebo.

• mechanism: Ernst has suggested that this is a pharmacokinetic interaction due induction of Cytochrome P450 enzymes by Hypericum extracts.
(Johne A, et al, cited in Ernst E. Lancet, Dec 11th.1999:354, 9195.)

• herbal concern: Patients stabilized on digoxin should advise their prescribing physician before consuming extracts of Hypericum .

herbs affecting drug toxicity: Potassium-depleting Herbs, including laxatives and diuretics.

• mechanism - cathartics and purgatives: Many herbal cathartics act via anthraquinone constituents causing irritation of the large bowel. Other purgatives contain cucurbitacins which are drastic purgatives not used in herbal medicine. Mild herbal laxatives act hepatically to increase bile flow and are unlikely to cause diarrhea. Theoretically, herbal cathartics are subject to laxative abuse as are commercial pharmaceutical laxatives. Excessive doses or chronic inappropriate use of such herbs could cause diarrhea leading to electrolyte depletion and hence potassium loss in the stool.

Common herbs containing anthraquinones:
• Aloe spp. (Aloe)
• Cassia spp. (Senna)
• Rhamnus catharticus (Buckthorn bark)
• Rhamnus purshiana (Cascara bark)
• Rheum officinale (Chinese Rhubarb)
• Rheum palmatum (Turkey Rhubarb)
• Rumex crispus (Yellow Dock)
• Tabebuia impetiginosa (Pau D'Arco)

• mechanism - diuretics: Herbal diuretics act in different ways, generally resulting in increased volume of diluted urine. Some herbs described as "diuretic" are in fact anti-inflammatory (demulcents) or antiseptic agents rather than aquaretics. In herbal therapeutics cardiac edema is specifically treated with Taraxacum fol (Dandelion Leaf), which has a diuretic strength equivalent to furosemide but contains high enough concentrations of potassium to make supplementation unnecessary. Herbal diuretics if used chronically in excessive amounts may cause potassium depletion via loss in the urine.

Common herbs with diuretic activity:
• Achillea millefolium (Yarrow)
• Agropyron repens (Couch Grass rhizome)
• Arctium lappa (Burdock)
• Arctostaphylos uva-ursi (Bearberry)
• Aphanes arvensis (Parsley Piert)
• Apium graveolens (Celery Seed)
• Barosma betulina (Buchu)
• Camellia sinensis (Tea)
• Chimaphila umbellata (Pipsissewa)
• Coffea arabica (Coffee beans)
• Cola nitida (Kola)
• Collinsonia canadensis (Stone Root)
• Cytisus scoparius (Scotch Broom)
• Daucus carota (Wild Carrot)
• Equisetum spp. (Horsetail)
• Eupatorium perfoliatum (Boneset)
• Eupatorium purpureum (Gravel Root)
• Galium aparine (Cleavers)
• Herniaria glabra (Rupturewort)
• Ilex paraguariensis (Maté)
• Juniperis communis (Juniper berries)
• Ononis spinosa (Spiny Restharrow)
• Orthosiphon spp. (Java Tea)
• Parietaria diffusa (Pellitory of the Wall)
• Paullinia cupana (Guarana)
• Petroselinum crispum (Parsley)
• Peumus boldo (Boldo)
• Rehmannia glutinosa (Chinese Foxglove)
• Sambucus nigra (Elder)
• Serenoa repens (Saw Palmetto)
• Solidago virgaurea (Golden Rod)
• Taraxacum officinale (Dandelion leaf)
• Theobroma cacao (Cacao)
• Tilia europaea (Linden flower)
• Urtica spp. (Stinging Nettle)
• Zea mays (Cornsilk)

See also: Hypotensive and Bradycardic Herbs

Please read the disclaimer concerning the intent and limitations of the information provided here.
Do not rely solely on the information in this article.

References

al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis 1994 Nov;24(5):737-752. (Review)

American Herbal Products Association. Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997.

Brinker F. Botanical Medicine Research Summaries. In: Eclectic Dispensatory of Botanical Therapeutics, Vol. II. Sandy, OR: Eclectic Medical Publications, 1995.

Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic Institute, 1997.

Brinker F. To Health With Herbs from Eclectic Dispensatory of Botanical Therapeutics. Vol. I, Alstat, E (comp.). Portland, OR: Eclectic Medical Publications, 1989.

Brinker F. The Toxicology of Botanical Medicines. Rev. 2nd ed., Sandy, OR: Eclectic Medical Publications, 1996.

BHP. The British Herbal Pharmacopeia, BHMA, Bournemouth, UK, 1983.

Cohen L, Kitzes R. JAMA 1984;251:730. (Letter)

Cohen L, Kitzes R. Magnesium sulfate and digitalis-toxic arrhythmias. JAMA 1983 May 27;249(20):2808-2810.
Abstract: Seven patients with congestive heart failure receiving long-term diuretic treatment (more than three years) experienced idionodal tachycardia in the presence of apparently normal serum digoxin levels. Intravenous bolus administration of magnesium (Mg) sulfate, followed by intramuscular Mg repletion, abolished the digitalis-toxic arrhythmia. The finding of decreased lymphocyte Mg and potassium contents proved the existence of cellular Mg depletion associated with normal serum Mg levels in five patients and with hypomagnesemia in the other two. Decreased cellular Mg content with normal serum Mg level predisposes to digitalis-toxic arrhythmias.

D'Arcy PF. Adverse reactions and interactions with herbal medicines. Part 2 - Drug interactions. Adverse Drug React. Toxicol Rev. 12:147-162, 1993.

De Smet PAGM, et al. (eds.). Adverse Effects of Herbal Drugs 2. Berlin: Springer-Verlag, 1993.

Ernst E. Second thoughts about safety of St. John's Wort. Lancet. Dec 11th.1999;354, 9195.

Felter, Harvey W, and Lloyd, John Uri. King's American Dispensatory. Sandy, OR: Eclectic Medical Publications, 1993.

Gugler R, Allgayer H. Effects of antacids on the clinical pharmacokinetics of drugs. An update. Clin Pharmacokinet. 1990 Mar;18(3):210-219. (Review)

Hall D, Kraus F, Rudolph W. [Drug interactions with digitalis glycosides]. Herz 1993 Apr;18(2):124-134. [Article in German]

Hochrein H. [Liver toxicity of digitalis glycosides]. Dtsch Med Wochenschr 1975 Apr 18;100(16):913. (Letter) [Article in German]

Huupponen R, Seppala P, Iisalo E. Effect of guar gum, a fibre preparation, on digoxin and penicillin absorption in man. Eur J Clin Pharmacol 1984;26(2):279-281.
Abstract: The effect of guar gum on the absorption of digoxin and phenoxymethyl penicillin was studied in a double blind study in 10 healthy volunteers. Guar gum reduced serum digoxin concentration during the early absorption period, but a similar amount of digoxin was found in 24 h urine whether given with or without guar gum. Both the peak penicillin concentration and the area under the serum curve were significantly reduced by the gum.

Johnson BF, Rodin SM, Hoch K, Shekar V. The effect of dietary fiber on the bioavailability of digoxin in capsules. J Clin Pharmacol 1987 Jul;27(7):487-490.
Abstract: Sixteen healthy volunteers were regularly given 0.4 mg of digoxin daily as two capsules with breakfast. After ten days during which breakfast was supplemented with 11 g of bran fiber, steady-state predose mean serum digoxin was lower (0.89 +/- 0.19 versus 0.84 +/- 0.18 ng/mL, P less than .05) and mean 24-hour area under curve determination was lower (30.5 +/- 6.1 versus 28.4 +/- 6.0 ng X hr/mL, P less than .05) than during the control period without bran. Height and time of peak serum digoxin, and 24-hour urinary digoxin were not significantly different. The 6 to 7% reduction in digoxin absorption from capsules is less than that reported from tablets and is probably clinically unimportant.

Kelly RA, Smith TW. Recognition and management of digitalis toxicity. Am J Cardiol. 1992 Jun 4;69(18):108G-118G; disc. 118G-119G. (Review)

Kinlay S, Buckley NA. Magnesium sulfate in the treatment of ventricular arrhythmias due to digoxin toxicity. J Toxicol Clin Toxicol 1995;33(1):55-59.
Abstract: Although digoxin antibodies are the definitive treatment of cardiac arrhythmias due to digoxin toxicity, magnesium can also be effective especially with low serum magnesium levels. The case report describes a patient with digoxin toxicity, ventricular tachycardia and a slightly elevated serum magnesium. Two 10 mmol doses of intravenous magnesium sulfate were associated with a more stable junctional rhythm with bigeminy. Magnesium is known to suppress early after depolarizations, and in supraphysiological doses, may act as an indirect antagonist of digoxin at the sarcolemma Na(+)-K(+)-ATPase pump. Intravenous magnesium may be used to treat cardiac arrhythmias due to digoxin poisoning where there is likely to be a delay in the availability of digoxin antibodies, even in the presence of elevated serum magnesium.

Kupfer S, Kosovsky JD. Effects of cardiac Glycosides on renal tubular transport of calcium, magnesium inorganic phosphate and glucose in the dog. J Clin Invest 1965 44:1132-1143.

Landauer JA. Magnesium deficiency and digitalis toxicity. JAMA 1984 Feb 10;251(6):730. (Letter, Review)

Lewis R, Durnin C, McLay J, McEwen J, McDevitt DG. Magnesium deficiency may be an important determinant of ventricular ectopy in digitalised patients with chronic atrial fibrillation. Br J Clin Pharmacol. 1991 Feb;31(2):200-203
Abstract: Digitalised patients with chronic atrial fibrillation (AF) have a high prevalence of ventricular premature beats (VPB); magnesium deficiency may be a contributory factor. We have used a magnesium loading-test to examine the relationship between ventricular ectopy and magnesium status in 14 digitalised patients with chronic AF. Among seven patients with infrequent VPB (less than 250 24 h-1; mean 107 24 h-1) mean magnesium retention was 10.1% and four subjects retained no significant quantities of magnesium, indicating magnesium repletion. Among the remaining seven patients, mean magnesium retention was significantly higher (33.1%, P less than 0.02) and all patients retained 20% or more of the load given. There was an overall relationship between Mg retention and numbers of VPB (rs = 0.54; P less than 0.05). Magnesium deficiency may be determinant of ventricular ectopy in digitalised patients with chronic AF.

Lewis, WH, Elvin-Lewis, MPF. Medical Botany. New York: John Wiley and Sons, 1977.

Longerich L, Johnson E, Gault MH. Digoxin-like factors in herbal teas. Clin Invest Med 1993 Jun;16(3):210-218.
Abstract: Forty-six commercially packaged teas and 78 teas prepared from purchased herbs were assayed for digoxin-like factors (DLF) by their crossreactivity with digoxin antibody (immuno-crossreactive DLF) and by their inhibition of ouabain binding to membrane Na,K-ATPase (NKA inhibitory DLF). Three packaged teas and 3 herbs gave NKA inhibitory DLF values > 30 micrograms digoxin equivalents/cup. Two packaged teas and 3 herbs gave immuno-crossreactive DLF values > .050 micrograms digoxin equivalent/cup. One herb, pleurisy root, had a crossreactive DLF value of 187 micrograms/cup and NKA inhibitory DLF equivalent to 3658 micrograms/cup. Plasma digoxin-like factors were measured after ingestion of the 3 commercially packaged herbal teas with highest values for NKA inhibitory DLF. After ingestion of each of the 3 teas, plasma NKA inhibitory DLF increase, in one case more than 100-fold. Two teas produced a measurable increase in plasma immuno-crossreactive DLF after ingestion. Some digoxin-like factors in human plasma may have a dietary source.

Lust J. The Herb Book. New York: Bantam Books, 1974.

Marz R. Medical Nutrition From Marz, Second Edition. Portland, OR: Omni-Press, 1997.

McRae S. Elevated serum digoxin levels in a patient taking digoxin and Siberian ginseng. CMAJ. 1996 Aug 1;155(3):293-295.
Abstract: A 74-year-old man taking a constant dose of digoxin for many years was found to have an elevated serum digoxin level with no signs of toxic effects. Common causes of elevated serum digoxin were ruled out, and the patient's digoxin level remained high after digoxin therapy was stopped. The patient then revealed that he was taking Siberian ginseng, a popular herbal remedy. The patient stopped taking ginseng, and the serum digoxin level soon returned to an acceptable level. The digoxin therapy was resumed. The patient resumed taking ginseng several months later, and the serum digoxin level again rose. Digoxin therapy was maintained at a constant daily dose, the ginseng was stopped once more, and the serum digoxin levels again returned to within the therapeutic range. It is unclear whether some component of the ginseng was converted to digoxin in vivo, interfered with digoxin elimination or caused a false serum assay result. The author cautions physicians to be alert to the potential for herbal remedies to interact with prescribed medications and to affect biochemical analyses.


Newall C, Anderson L, Phillipson JD. Herbal Medicines: A Guide for Health-care Professionals. London: The Pharmaceutical Press, 1996.

Rodin SM, Johnson BF. Pharmacokinetic interactions with digoxin. Clin Pharmacokinet. 1988 Oct;15(4):227-244.

Roe DA. Diet and Drug Interactions. New York: Van Nostrand Reinhold, 1989.

Ryan MP. Interrelationships of magnesium and potassium homeostasis. Miner Electrolyte Metab 1993;19(4-5):290-295.
Abstract: The interrelationships of magnesium (Mg) and potassium (K) homeostasis are reviewed. Evidence from clinical and experimental studies including whole animal and cell culture experiments indicate that (1) homeostasis of Mg and K are closely related in the whole organism, (2) deficiencies of Mg and K frequently co-exist with gastrointestinal and especially renal losses from diuretic and nephrotoxic drug treatment being mainly responsible, and (3) Mg is required for maintenance of normal cellular K. Evidence from many laboratories indicate that Mg has direct effects at a cellular level on K transport. These include effects on Na-K-ATPase, Na-K-Cl cotransport, K channels, charge screening and permeability effects on membranes. New data on positive correlations between Mg and K in cardiac tissue, skeletal muscle and lymphocytes from patients undergoing cardiopulmonary bypass are presented. Interrelationships in Mg and K in cardiac tissue have probably the greatest clinical significance in terms of arrhythmias, digoxin toxicity, and myocardial infarction. Future studies will be aimed at elucidating mechanisms of Mg-K interrelationships at a cellular level using new techniques with the ability to detect concentrations and modulations of free intracellular Mg.

Schmidt TA, Bundgaard H, Olesen HL, Secher NH, Kjeldsen K. Digoxin affects potassium homeostasis during exercise in patients with heart failure. Cardiovasc Res 1995 Apr;29(4):506-511.
Abstract: OBJECTIVE: The aim was to evaluate whether digitalisation of heart failure patients affects extrarenal potassium handling during and following exercise, and to assess digoxin receptor occupancy in human skeletal muscle in vivo. METHODS: In a paired study of before versus after digitalisation, 10 patients with congestive heart failure underwent identical exercise sessions consisting of three bouts of increasing work rates, 41-93 W, on a cycle ergometer. The final bouts were followed by exercise to exhaustion. The femoral vessels and brachial artery were catheterised. Arterial blood pressure, heart rate, leg blood flow, cardiac output, plasma potassium, haemoglobin, pH, and skeletal muscle receptor occupancy with digoxin in biopsies were determined. RESULTS: Occupancy of skeletal muscle Na/K-ATPase with digoxin was 9% (P < 0.05). Following digitalisation femoral venous plasma potassium increased by 0.2-0.3 mmol.litre-1 (P < 0.05) at work rates of 69 W, 93 W, and at exhaustion, as well as during the first 3 min of recovery. Following digitalisation the femoral venoarterial difference in plasma potassium increased by 50-100% (P < 0.05) during exercise, and decreased by 66-75% (P < 0.05) during early recovery. Total loss of potassium from the leg increased by 138%. The effects of digitalisation on plasma potassium were not the outcome of changes in haemodynamics, because cardiac output and leg blood flow increased by up to 13% and 19% (P < 0.05), nor was it the outcome of changes in haemoconcentration or pH. CONCLUSIONS: Extrarenal potassium handling is altered as a result of digoxin treatment. This is likely to reflect a reduced capacity of skeletal muscle Na/K-ATPase for active potassium uptake because of inhibition by digoxin, adding to the reduction of skeletal muscle Na/K-ATPase concentration induced by heart failure per se. In heart failure patients, improved haemodynamics induced by digoxin may, however, increase the capacity for physical conditioning. Thus the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by training.

Sueta CA, Patterson JH, Adams KF Jr. Antiarrhythmic action of pharmacological administration of magnesium in heart failure: a critical review of new data. Magnes Res 1995 Dec;8(4):389-401.
Abstract: Congestive heart failure is characterized by contractile dysfunction and frequent complex ventricular ectopy. Despite advances in therapy, mortality from heart failure is substantial, estimated at 10-80 percent per year, and sudden death is common. Magnesium is the second most common intracellular cation, strongly influences cardiac cell membrane function, and is an important catalyst of many enzymatic reactions in the myocyte. Epidemiological studies have implicated magnesium deficit in the genesis of sudden death. Patients with congestive heart failure are predisposed to magnesium deficit for many reasons, including neurohormonal activation, poor gastrointestinal absorption, and drug therapy. Hypomagnesaemia is common in these patients and has been linked to an increased frequency of complex ventricular ectopy. Several early, uncontrolled studies have suggested a beneficial effect of magnesium administration on ventricular arrhythmias in patients with congestive heart failure. Two recent randomized, double blind, placebo-controlled trials have shown that both intravenous and oral administration of magnesium chloride results in a significant reduction in the frequency and complexity of ventricular arrhythmias in patients with congestive heart failure. Magnesium administration is well tolerated and serious adverse effects are rare. The potential mechanisms of the antiarrhythmic action of magnesium and limitations of the available data are discussed. The evidence reviewed suggests that serum magnesium concentrations should be monitored and corrected in patients with congestive heart failure. Ventricular arrhythmias may respond to acute intravenous magnesium administration, which should be considered as early therapy. Further study is needed to define magnesium dose and the effect of concomitant potassium administration. A prospective clinical trial is warranted to determine the chronic effects of magnesium administration in patients with heart failure.

Toffaletti J. Electrolytes, divalent cations, and blood gases (magnesium). Analyt Chem 1991 63(12):192R-194R.

Weiss RF. Herbal Medicine. Beaconsfield, England: Beaconsfield Publishers Ltd., 1988.

Whang R, Oei TO, Watanabe A. Frequency of hypomagnesemia in hospitalized patients receiving digitalis. Arch Intern Med 1985 Apr;145(4):655-656.
Abstract: We examined the frequency of hypokalemia and hypomagnesemia in patients receiving digitalis. Serum sodium, magnesium, and potassium levels were determined in 136 serum samples sent to the laboratory for digoxin assay. Hyponatremia (less than or equal to 130 mEq/L) occurred most frequently (21%), followed by hypomagnesemia (less than or equal to 1.25 mEq/L) in 19%, hypokalemia (less than or equal to 3.5 mEq/L) in 9%, and hypermagnesemia (greater than or equal to 2.25 mEq/L) in 7%. The twofold frequency of hypomagnesemia (19%) contrasted with hypokalemia (9%) indicates that clinicians are more attuned to avoiding hypokalemia than hypomagnesemia in patients receiving digitalis. Because hypokalemia and/or hypomagnesemia may contribute to the toxic effects of digitalis, ourobservation suggests that hypomagnesemia may be a more frequent contributor than hypokalemia to induction of toxic reactions to digitalis. Routine serum magnesium determination in patients receiving digitalis, who often are also receiving potent diuretics, may assist in identifying additional patients at risk for the toxic effects of digitalis.

Young IS, Goh EM, McKillop UH, Stanford CF, Nicholls DP, Trimble ER.  Magnesium status and digoxin toxicity. Br J Clin Pharmacol. 1991 Dec;32(6):717-721.
Abstract: 1. Eighty-one hospital patients receiving digoxin were separated into groups with and without digoxin toxicity using clinical criteria. Serum digoxin, sodium, potassium, calcium, creatinine, magnesium and monocyte magnesium concentrations were compared. 2. Subjects with digoxin toxicity had impaired colour vision (P less than 0.0001, Farnsworth-Munsell 100 hue test) and increased digoxin levels (1.89 (1.56-2.21) vs 1.34 (1.20-1.47) nmol l-1, P less than 0.01) (mean (95% confidence limits], though there was considerable overlap between two groups. 3. Subjects with digoxin toxicity had lower levels of serum magnesium (0.80 (0.76-0.84) vs 0.88 (0.85-0.91) mmol l-1, P less than 0.01) and monocyte magnesium (6.40 (5.65-7.16) vs 8.76 (7.81-9.71) mg g-1 DNA, P less than 0.01), but there were no significant differences in other biochemical parameters. A greater proportion of toxic subjects were receiving concomitant diuretic therapy (20/21 vs 37/60, P less than 0.05). 4. Magnesium deficiency was the most frequently identified significant electrolyte disturbance in relation to digoxin toxicity. In the presence of magnesium deficiency digoxin toxicity developed at relatively low serum digoxin concentrations.

Zilly W, Kuhlmann J, Kasper H, Richter E. [Effect of a fiber-rich diet on digoxin resorption]. Med Klin [Prax] 1982 Sep 10;77(19):42-48. [Article in German]
Abstract: In five female healthy volunteers the influence of dietary fiber (wheat bran or carob seed flour) on absorption of digoxin was investigated. Five minutes after ingestion of a formula diet alone or in combination with wheat bran or carob seed flour 0,8 mg beta-acetyldigoxin was given per os. The plasmaconcentration-time curve over eight hours, the area under curve and the cumulative urinary excretion were not changed significantly. It was concluded that there is no influence of dietary fiber on rate or degree of digoxin-absorption.