Interaction between digoxin and calcium antagonists and antiarrhythmic drugs

Belz, G. G.; Doering, W.; Munkes, R.; Matthews, Jennifer H.

doi:10.1038/clpt.1983.55

Cited by 152 publications

(56 citation statements)

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“…Clinical drug-drug interactions were reported in the literature between digoxin (a good P-gp substrate) and other drugs, such as quinidine [97][98][99], verapamil [100 -102], talinolol [103], clarithromycin [104], itraconazole [105], erythromycin [106], and propafenone [101,107,108].…”

Section: Drug-drug Interactionsmentioning

confidence: 99%

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

et al. 2007

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Key Words. P-glycoprotein • Drug interaction • Complementary and alternative medicine • CAM • Pharmacokinetics Pharmacodynamics LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify important sources of variability in drug exposure caused by drug interactions mediated by P-glycoprotein.2. Describe how unwanted drug-drug interactions may lead to unexpected serious toxicity or undertreatment.3. Prevent these interactions by individualizing pharmacotherapy; this means selecting noninteracting drugs or adapting the dose of (the) interacting drug(s).Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThe importance of P-glycoprotein (P-gp) in drug-drug interactions is increasingly being identified. P-gp has been reported to affect the pharmacokinetics of numerous structurally and pharmacologically diverse substrate drugs. Furthermore, genetic variability in the multidrug resistance 1 gene influences absorption and tissue distribution of drugs transported. Inhibition or induction of P-gp by coadministered drugs or food as well as herbal constituents may result in pharmacokinetic interactions leading to unexpected toxicities or undertreatment. On the other hand, modulation of P-gp expression and/or activity may be a useful strategy to improve the pharmacological profile of anticancer P-gp substrate drugs. In recent years, the use of complementary and alternative medicine (CAM), like herbs, food, and vitamins, by cancer patients has increased significantly. CAM use substantially increases the risk for interactions with anticancer drugs, especially because of the narrow therapeutic window of these compounds. However, for most CAMs, it is unknown whether they affect metabolizing enzymes and/or drug transporter activity. Clinically relevant interactions are reported between St John's wort or grapefruit juice and anticancer as well as nonanticancer drugs. CAM-drug interactions could explain, at least in part, the large interindividual variation in efficacy and toxicity associated with drug therapy in both cancer and noncancer patients.

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Section: Drug-drug Interactionsmentioning

confidence: 99%

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

et al. 2007

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“…A reduction in renal and non-renal clearance of digoxin is considered to be the source of the calcium antagonist-digoxin interference [12,13]. The increased digoxin plasma levels caused by concurrent administration of a calcium channel blocker are pharmacodynamically relevant, meaning that there is evidence for an enhanced positive inotropic effect due to the elevated digoxin concentrations [1]. Furthermore the alterations in the pharmacokinetics of digoxin caused by calcium antagonists lead to an increased risk of digitalis intoxication especially in the elderly [14].…”

Section: Introductionmentioning

confidence: 99%

“…Various calcium antagonists increase the plasma concentrations of digoxin [1][2][3][4][5][6][7][8]. Dihydropyridine substances (e.g.…”

Section: Introductionmentioning

confidence: 99%

The interaction of the calcium antagonist RO 40‐5967 with digoxin.

Siepmann

Kleinbloesem

Kirch

1995

Brit J Clinical Pharma

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1. The interaction of the newer calcium antagonist Ro 40‐5967 with digoxin was investigated in 42 healthy subjects under steady state conditions. 2. After an adequate loading dose digoxin 0.375 mg once daily was given alone for 1 week. Afterwards three different doses (50, 100, 150 mg daily) of the calcium antagonist Ro 40‐5967 were administered to three groups of 14 subjects each for 1 week concurrently with digoxin 0.375 mg daily. 3. Ro 40‐5967 led to an increase of mean maximum digoxin plasma concentrations (Cmax) and AUC. For AUC this effect was significantly dose‐dependent. 4. Increasing doses of the calcium antagonist led to a stepwise rise of the PQ‐time in ECG. 5. A slight fall of heart rate was seen after a 7 day treatment of digoxin alone. This effect was more pronounced when Ro 40‐5967 was added to the medication. No significant changes of stroke volume and blood pressure were noted. 6. In conclusion Ro 40‐5967 led to a significant elevation of the plasma concentration‐time curve (AUC) of digoxin. This effect was dose‐dependent.

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“…Cardiac arrhythmia sometimes occurs in patients who are taking digoxin, 1,2) and thus antiarrhythmic drugs were often co-administrated with digoxin. In fact, antiarrhythmic or antianginal drugs were also prescribed for 25% and 21% of patients taking digoxin, respectively, in our hospital.3) Digoxin is well known to have only a narrow therapeutic concentration range (trough: 0.5-2.0 ng/ml), and to be prone to drug-drug interaction.4) Clinical reports suggested that the serum concentration of digoxin was elevated by amiodarone, 5-7) quinidine, [8][9][10] verapamil 11,12) and nicardipine, 13) and the daily dose of digoxin is adjusted based on a sophisticated serial monitoring of serum digoxin concentration.Digoxin has been found to be mainly excreted by tubular secretion and glomerular filtration, 4,14) and tubular secretion has been demonstrated to be mediated via MDR1 by using LLC-GA5-COL150 cells, which were established by transfection of MDR1 cDNA into porcine kidney epithelial LLC-PK 1 cells. 15,16) Herein, the effects of amiodarone, its active metabolite monodesethyl-amiodarone (DEA) amd quinidine on the transport of [ 3 H]digoxin was examined using LLC-GA5-COL150 cells to elucidate whether MDR1 was responsible for the drug interaction between digoxin and amiodarone or quinidine found in clinical use.…”

mentioning

confidence: 99%

“…4) Clinical reports suggested that the serum concentration of digoxin was elevated by amiodarone, 5-7) quinidine, [8][9][10] verapamil 11,12) and nicardipine, 13) and the daily dose of digoxin is adjusted based on a sophisticated serial monitoring of serum digoxin concentration.…”

mentioning

confidence: 99%

MDR1-Mediated Interaction of Digoxin with Antiarrhythmic or Antianginal Drugs.

Kakumoto

Takara

Sakaeda

et al. 2002

Biological & Pharmaceutical Bulletin

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Digoxin, a cardiac glycoside, is mainly prescribed for patients with congestive heart failure. Cardiac arrhythmia sometimes occurs in patients who are taking digoxin, 1,2) and thus antiarrhythmic drugs were often co-administrated with digoxin. In fact, antiarrhythmic or antianginal drugs were also prescribed for 25% and 21% of patients taking digoxin, respectively, in our hospital.3) Digoxin is well known to have only a narrow therapeutic concentration range (trough: 0.5-2.0 ng/ml), and to be prone to drug-drug interaction.4) Clinical reports suggested that the serum concentration of digoxin was elevated by amiodarone, 5-7) quinidine, [8][9][10] verapamil 11,12) and nicardipine, 13) and the daily dose of digoxin is adjusted based on a sophisticated serial monitoring of serum digoxin concentration.Digoxin has been found to be mainly excreted by tubular secretion and glomerular filtration, 4,14) and tubular secretion has been demonstrated to be mediated via MDR1 by using LLC-GA5-COL150 cells, which were established by transfection of MDR1 cDNA into porcine kidney epithelial LLC-PK 1 cells. 15,16) Herein, the effects of amiodarone, its active metabolite monodesethyl-amiodarone (DEA) amd quinidine on the transport of [ 3 H]digoxin was examined using LLC-GA5-COL150 cells to elucidate whether MDR1 was responsible for the drug interaction between digoxin and amiodarone or quinidine found in clinical use. The possibility of interaction with other antiarrhythmic drugs, cibenzoline, lidocaine, disopyramide and mexiletin, and antianginal drugs, dipyridamole and isosorbide, was also examined. These are selected because they are more frequently used with digoxin compared with others, at least in our hospital. MATERIALS AND METHODS ChemicalsCibenzoline was a gift from Fujisawa Pharmaceutical Co., Ltd. (Osaka, Japan). DEA was a gift from Taisho Pharmaceutical Co., Ltd. (Tokyo, Japan). Amiodarone, mexiletin and quinidine were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). Disopyramide, lidocaine, dipyridamole and colchicine were purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Isosorbide was purchased from Alexis Co. (San Diego, CA, U.S.A.). [3 H]Digoxin (595.7 GBq/mmol) was purchased from Du Pont-New England Nuclear (Boston, MA, U.S.A.). Unlabeled digoxin was purchased from Aldrich Chemical Co. (Milwaukee, WI, U.S.A.). All other chemicals were of the highest purity available.Culture of LLC-PK 1 and LLC-GA5-COL150 Cells LLC-GA5-COL150 cells were established by transfection of human MDR1 cDNA into porcine kidney epithelial LLC-PK 1 cells.15,16) LLC-PK 1 and LLC-GA5-COL150 cells were maintained in the culture medium consisting of Medium199 (Dainippon Pharmaceutical Co. Ltd., Osaka, Japan) supplemented with 10% fetal bovine serum (FBS; BioWhittaker, Walkersville, MD, U.S.A.), with no antibiotics. Colchicine was also added to a final concentration of 150 ng/ml only for LLC-GA5-COL150 cells. LLC-PK 1 (1.0ϫ10 6 cells/100 mm 2 ) and LLC-GA5-COL150 cells (1.5ϫ10 6 cells/100 mm 2 ) were seeded on plastic cu...

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Interaction between digoxin and calcium antagonists and antiarrhythmic drugs

Cited by 152 publications

References 5 publications

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein)

The interaction of the calcium antagonist RO 40‐5967 with digoxin.

MDR1-Mediated Interaction of Digoxin with Antiarrhythmic or Antianginal Drugs.

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