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      Relevancia clínica de la interacción entre posaconazol y digoxina: a propósito de un caso Translated title: Clinical relevance of the pharmacokinetic interaction between posaconazol and digoxin: a case report

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          Abstract

          Resumen El posaconazol es un inhibidor de la glicoproteína P (P-gp), un transportador dependiente del ATP que desempeña un papel importante en la absorción, distribución y eliminación de múltiples medicamentos. Varios estudios in vitro han demostrado que la digoxina es un sustrato de la P-gp, por lo que su administración concomitante puede dar lugar a un aumento de la absorción intestinal y/o a una disminución de la depuración renal, con el consiguiente riesgo de toxicidad digitálica. Se presenta el caso clínico de una intoxicación digitálica como consecuencia de la interacción entre posaconazol y digoxina en un paciente con fibrilación auricular, insuficiencia cardiaca y múltiples episodios de pancitopenia postquimioterapia por leucemia mieloide aguda. El paciente tuvo que ser hospitalizado por bradicardia de 30 l.p.m. Ambos medicamentos fueron suspendidos de inmediato y el paciente se recuperó sin incidencias.

          Translated abstract

          Summary Posaconazole is an inhibitor of glycoprotein P (P-gp), an ATP-dependent transporter with a role in drug absorption, distribution and elimination. Several in vitro studies have shown that digoxin is a substrate of P-gp, so concomitant administration may result in increased intestinal absorption and/or decreased renal clearance, with a consequent risk of digitalic toxicity. The clinical case of digitalis intoxication as a consequence of the interaction between posaconazole and digoxin in a patient with atrial fibrillation, congestic heart failure and multiple episodes of post-chemotherapy pancytopenia due to acute myeloid leukemia is weighed. The patient had to be hospitalized for bradicardia of 30 l.p.m. Both medicines were immediately suspended and the patient recovered without major issues.

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          Most cited references9

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          Proposal for a new tool to evaluate drug interaction cases.

          The assessment of causation for a potential drug interaction requires thoughtful consideration of the properties of both the object and precipitant drugs, patient-specific factors, and the possible contribution of other drugs that the patient may be taking. The Naranjo nomogram was designed to evaluate single-drug adverse events, not drug-drug interactions. Several of the questions on the Naranjo nomogram do not apply to potential drug-drug interactions, while others do not specify object or precipitant drug. Nevertheless, it has been inappropriately used to evaluate drug-drug interactions. The Drug Interaction Probability Scale (DIPS) was developed to provide a guide to evaluating drug interaction causation in a specific patient. It is intended to be used to assist practitioners in the assessment of drug interaction-induced adverse outcomes. The DIPS uses a series of questions relating to the potential drug interaction to estimate a probability score. An accurate assessment using the DIPS requires knowledge of the pharmacologic properties of both the object and precipitant drugs. Inadequate knowledge of either the drugs involved or the basic mechanisms of interaction will be a limitation for some users. The DIPS can also serve as a guide in the preparation of articles describing case reports of drug interactions, as well as in the evaluation of published case reports.
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            Drug-drug interactions mediated through P-glycoprotein: clinical relevance and in vitro-in vivo correlation using digoxin as a probe drug.

            The clinical pharmacokinetics and in vitro inhibition of digoxin were examined to predict the P-glycoprotein (P-gp) component of drug-drug interactions. Coadministered drugs (co-meds) in clinical trials (N = 123) resulted in a small, 0.1 is predictive of clinical digoxin interactions (AUC and C(max)).
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              Risk of digoxin intoxication in heart failure patients exposed to digoxin-diuretic interactions: a population-based study.

              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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                Author and article information

                Journal
                ofil
                Revista de la OFIL
                Rev. OFIL·ILAPHAR
                Organización de Farmacéuticos Ibero-Latinoamericanos (Madrid, Madrid, Spain )
                1131-9429
                1699-714X
                September 2021
                : 31
                : 3
                : 327-329
                Affiliations
                [1] Madrid orgnameHospital Universitario Fundación Jiménez Díaz orgdiv1Servicio de Farmacia España
                [2] Leganés Madrid orgnameHospital Universitario Severo Ochoa orgdiv1Servicio de Farmacia España
                Article
                S1699-714X2021000300327 S1699-714X(21)03100300327
                10.4321/s1699-714x20210003000014
                f1cc1582-2e41-4307-9af1-d99b8aa34513

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 17 May 2020
                : 01 May 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 9, Pages: 3
                Product

                SciELO Spain

                Categories
                Casos Clínicos

                P-glycoprotein,posaconazol,digoxina,interacciones farmacológicas,Glicoproteína P,posaconazole,digoxin,drug interactions

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