Risk of digoxin intoxication caused by clarithromycin–digoxin interactions in heart failure patients: a population-based study

Chan, Agnes L. F.; Wang, Meng Ting; Su, Chen Yi; Tsai, Fu Hsiung

doi:10.1007/s00228-009-0698-4

Cited by 19 publications

(9 citation statements)

References 30 publications

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“…Under this system, the DDD for one drug is assumed to be functionally equivalent to the DDD for any other drug used for a similar indication. Although primarily intended for use in drug utilization research, the system is also commonly used in cohort studies investigating outcomes of treatment including AEDs (Canevini et al., 2010) and non‐AEDs (De Bruin et al., 2007; Chan et al., 2009). However, the assignment of DDD for the individual AEDs may not be justifiable at first glance.…”

Section: Discussionmentioning

confidence: 99%

Effect of dosage failed of first antiepileptic drug on subsequent outcome

et al. 2012

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SUMMARYPurpose: The recent definition of drug-resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the doses at which the first and second AED regimens failed on subsequent outcomes in a population of adults with newly diagnosed epilepsy followed for up to 20 years. Methods: Patients in whom epilepsy was diagnosed and the first AED prescribed between July 1, 1982 and April 1, 2006, were followed until March 31, 2008. Dosage at which an AED failed was categorized according to the World Health Organization's defined daily dose (DDD) for each drug. Cumulative incidence curves for time to final seizure freedom (no seizure for at least 1 year on unchanged dosage at last follow up) were stratified by whether the first regimen was failed at doses above or below the 25%, 50%, or 75% cutoffs for the DDD of each AED.Key Findings: Among patients who had taken a second regimen (n = 327), those in whom the first AED failed at doses above the various cutoffs (particularly 50% and 75% DDD) had lower probability of becoming seizure-free at last follow-up (p = 0.06 for 25% DDD, p < 0.001 for both 50% and 75% DDD). The same difference was observed for patients who had taken a third regimen (n = 141; p = 0.23 for 25% DDD, p < 0.01 for 50% DDD; and p = 0.002 for 75% DDD). A trend to higher seizure-free rate was observed in patients who had taken the third regimen when both the first and second regimens failed at <75% DDD. The difference remained significant after adjusting for covariates when using 50% DDD as the cutoff for patients who took a second regimen (hazard ratio 1.60, 95% confidence interval 1.08-2.37). Significance: Higher failure dosage of the first AED predicts poorer subsequent outcome. This methodology could be used to refine further the ILAE definition of drug-resistant epilepsy by exploring the doses need to fail to provide an adequate AED trial.

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Section: Discussionmentioning

confidence: 99%

Effect of dosage failed of first antiepileptic drug on subsequent outcome

et al. 2012

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“…Table 1 shows the clinical and demographical characteristics of the cases and matched controls. Part of the baseline characteristics data of the cases has been reported elsewhere in an evaluation of the adverse clinical outcomes caused by a digoxin‐clarithromycin interaction [35]. Cases and matched controls were comparable in the matching variables: mean age (77.1 vs. 77.1 years), gender (percentage of female, 67.9 vs. 68.1), presence of chronic kidney disease (37.8 vs. 36.1%), and median duration of digoxin use before the index date (83 vs. 90 days).…”

Section: Resultsmentioning

confidence: 99%

Risk of digoxin intoxication in heart failure patients exposed to digoxin–diuretic interactions: a population‐based study

Wang¹,

Chan

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Increased frequency of electrolyte abnormalities and cardiac arrhythmias among patients exposed to digoxin–diuretic interactions has been well‐documented in numerous descriptive studies. • Nonetheless, a clear causal relationship has not been established in these studies. WHAT THIS STUDY ADDS • The risks of digoxin intoxication associated with use of digoxin in combination with any diuretic use, types of diuretics, combinations of diuretics, and individual diuretics were quantified using a population‐based nested case–control study design. • The combined therapy of digoxin with any diuretic is associated with a 3.08‐fold increase in the risk of digoxin intoxication. • Regarding diuretic class, the risk carried by loop diuretics is greater than that of thiazides or potassium–sparing diuretics, and the risk varies with different combinations of diuretic classes and individual diuretics. AIMS To quantify the digoxin intoxication risk associated with exposure to digoxin–diuretic interactions, and evaluate whether the risk varies by diuretic type, individually or in combination. METHODS This was a population‐based nested case–control study in which data from the National Health Insurance Research Database (NHIRD) in Taiwan were analysed. RESULTS The study cohort comprised 154 058 heart failure (HF) patients taking digoxin between 2001 and 2004, in whom digoxin intoxication requiring a hospitalization (ICD‐9 code 972.1) occurred in 595 cases. A total of 28 243 matched controls were also selected for analysis. Cases were 3.08 times (adjusted OR 3.08, 95% CI 2.50, 3.79) more likely to have been prescribed diuretic medication in the previous month than controls. Regarding the class of diuretics, loop diuretics carried the greatest risk (adjusted OR 2.97, 95% CI 2.35, 3.75), followed by thiazides (OR 2.36, 95% CI 1.70, 3.29) and potassium‐sparing diuretics (OR 1.72, 95% CI 0.83, 3.56). The risk was also observed to vary with different combinations of diuretics, and the loops/thiazides/potassium‐sparing diuretics combination carried the greatest risk (adjusted OR 6.85, 95% CI 4.93, 9.53). Among the individual diuretics examined, hydrochlorothiazide carried the greatest risk (adjusted OR 4.63, 95% CI 2.50, 8.57). CONCLUSIONS This study provided empirical evidence that digoxin–diuretic interactions increased the risk of hospitalization for digoxin intoxication in HF patients. The risk was particularly high for concomitant use of digoxin with a combination of loop diuretics, thiazide and potassium‐sparing diuretics. The combined use of digoxin and diuretics should be avoided if possible.

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“…In patients with heart failure, this risk could be as high as 55.4-fold. 49 Oral Anticoagulants Many older adults with kidney disease require oral anticoagulation therapy. Warfarin is metabolized by cytochrome 2C9.…”

Section: Macrolidesmentioning

confidence: 99%

Drug Management in the Elderly Adult With Chronic Kidney Disease: A Review for the Primary Care Physician

Ponticelli

Sala

Glassock

2015

Mayo Clinic Proceedings

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With advancing age, the functional reserve of many organs tends to decrease. In particular, the lean body mass, the levels of serum albumin, the blood flow to the liver, and the glomerular filtration rate are reduced in elderly individuals and can be further impaired by the concomitant presence of acute or chronic kidney disease. Moreover, patients with kidney disease are often affected by comorbid processes and are prescribed multiple medications. The aging process also modifies some drug interactions, including the affinity of some drugs for their receptor, the number of receptors, and the cell responses upon receptor activation. Therefore, older patients with kidney disease are particularly susceptible to the risks of adverse drug reactions. Planning a pharmacological regimen in such patients is confounded by the paucity of information available on the pharmacokinetic and pharmacodynamic profiles of a large number of drugs commonly used in this group of patients. Finally, many aged patients suffer from unintentional poor compliance. In this review, the problems physicians face in designing safe and effective medication management in elderly individuals are discussed, paying attention to those more frequently used, which may be potentially harmful in patients with kidney disease. The risks of overdosing and underdosing are outlined, and some recommendations to reduce the risk of adverse drug reactions are provided. A review of the literature covering the field of drug management in older patients with kidney disease was performed by selecting those articles published between January 1, 1990, and December 1, 2014, using PubMed as a search engine with the keywords elderly, kidney disease, drugs, drug interaction, and renal function.

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Risk of digoxin intoxication caused by clarithromycin–digoxin interactions in heart failure patients: a population-based study

Cited by 19 publications

References 30 publications

Effect of dosage failed of first antiepileptic drug on subsequent outcome

Effect of dosage failed of first antiepileptic drug on subsequent outcome

Risk of digoxin intoxication in heart failure patients exposed to digoxin–diuretic interactions: a population‐based study

Drug Management in the Elderly Adult With Chronic Kidney Disease: A Review for the Primary Care Physician

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