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1.
Background:
Hyponatremia is a common electrolyte disorder and is associated with multiple comorbidities. Management strategies are varied and etiology-dependent. The use of tolvaptan, a vasopressin antagonist, outside of clinical trials has not been well characterized.Objectives:
To quantify tolvaptan compliance with institutional guidelines and make recommendations concerning reasonable expectations for its role in hyponatremia management.Methods:
This was a retrospective observational study in a 125-bed community hospital. Patients admitted in 2013 who received at least one dose of tolvaptan were included.Results:
Thirty-seven patient encounters were evaluated. Tolvaptan was prescribed with 83.7% adherence to the institutional order set. Mean age was 71 ± 16.4 years with 20 (54%) females. Hyponatremia was a contributory cause of admission in 15 (40.5%) patients and offending medications were discontinued in 7 (19%). Causes of hyponatremia included syndrome of inappropriate antidiuretic hormone (SIADH), heart failure, and cirrhosis in 78.3%, 8.2%, and 13.5% of participants, respectively. Management included fluid restriction in 19 (51%) and furosemide in 5 (13.5%), with tolvaptan administration on average 3.2 days after admission. Most patients (78.4%) required ≤2 doses. Sodium concentration was elevated 8 mEq/L by the end of hospitalization. Discharge to palliative care or death occurred in 8 (21.6%). Postdischarge review revealed 3 (8%) maintained sodium concentration ≥130 mEq/dL.Conclusion:
Tolvaptan was initiated after other interventions and with limited duration per institutional guidelines. This cohort had complicating underlying chronic diseases. These results will be used to refine recommendations with pharmacist input for risk/benefit stratification based on reasonable expectations. 相似文献2.
AIMS
In vitro studies indicated CYP3A4 alone was responsible for tolvaptan metabolism. To determine the effect of a CYP3A4 inhibitor (ketoconazole) and a CYP3A4 inducer (rifampicin) on tolvaptan pharmacokinetics (PK) and pharmacodynamics (PD), two clinical trials were performed.METHODS
For CYP3A4 inhibition, a double-blind, randomized (5:1), placebo-controlled trial was conducted in 24 healthy subjects given either a single 30 mg dose of tolvaptan (n = 19) or matching placebo (n = 5) on day 1 with a 72 h washout followed by a 3 day regimen of 200 mg ketoconazole, once daily with 30 mg tolvaptan or placebo also given on day 5. For CYP3A4 induction, 14 healthy subjects were given a single dose of 240 mg tolvaptan with 48 h washout followed by a 7 day regimen of 600 mg rifampicin, once daily, with 240 mg tolvaptan also given on the seventh day.RESULTS
When co-administered with ketoconazole, mean Cmax and AUC(0,∞) of tolvaptan were increased 3.48- and 5.40-fold, respectively. Twenty-four hour urine volume increased from 5.9 to 7.7 l. Erythromycin breath testing showed no difference following a single dose of tolvaptan. With rifampicin, tolvaptan mean Cmax and AUC were reduced to 0.13- and 0.17-fold of tolvaptan administered alone. Twenty-four hour urine volume decreased from 12.3 to 8.8 l.CONCLUSIONS
Tolvaptan is a sensitive CYP3A4 substrate with no inhibitory activity. Due to the saturable nature of tolvaptan''s effect on urine excretion rate, changes in the pharmacokinetic profile of tolvaptan do not produce proportional changes in urine output. 相似文献3.
《Expert opinion on pharmacotherapy》2013,14(6):961-976
Introduction: It has been > 25 years since it was first discovered that arginine vasopressin levels are elevated in heart failure and this elevation is proportional to the severity of heart failure. Tolvaptan is an oral nonpeptide V2-selective antagonist and has been shown to induce free water excretion without increasing urine sodium, an effect termed ‘aquaresis’. Areas covered: This paper aims to review the physiology, chemistry, pharmacokinetics, clinical efficacy and safety of tolvaptan in HF. A PubMed literature search was performed using ‘tolvaptan’ and the MeSH term ‘heart failure’, yielding 89 references. Expert opinion: Clinical trials conducted in ambulatory and hospitalized patients with HF have found treatment with tolvaptan causes rapid and sustained body weight reductions concurrent with increases in urine output, improves and/or normalizes serum sodium in hyponatremic patients, reduces signs and symptoms of congestion and increases thirst. However, tolvaptan has not been shown to decrease HF re-hospitalization or mortality. As an adjunct to standard therapy, tolvaptan is unique in that it is virtually the only novel agent tested in patients hospitalized for acute heart failure syndrome (AHFS) to reach its primary end point for short-term efficacy without causing deleterious side effects. There is theoretical concern that chronic V2 receptor blockade may cause harmful long-term side effects via enhanced V1a receptor activation, potentially offsetting any favorable effects on congestion and hyponatremia. The ‘vaptan’ class of drugs is an active and promising area for clinical investigation and future research is necessary to clarify the therapeutic role of selective and nonselective vasopressin inhibition in chronic HF and AHFS. 相似文献
4.
《Expert opinion on pharmacotherapy》2013,14(10):2181-2184
Despite diuretics being used to relieve the fluid retention/congestion associated with heart failure (HF), patients with HF are commonly hospitalised due to progressive volume retention with an increase in body weight and the deterioration of symptoms. Arginine vasopressin acts at vasopressin V2 receptors in the kidney as an antidiuretic. Tolvaptan is an orally-active selective V2-receptor antagonist. In the Acute and Chronic Therapeutic Impact of a Vasopressin antagonist in Congestive Heart Failure trial of patients hospitalised with HF, tolvaptan 30 mg/day increased urine volume and induced a weight loss of 3.3 kg at discharge (placebo; 1.9 kg). In post hoc analyses, mortality was lower with tolvaptan in patients with renal impairment and severe congestion, compared to placebo. Thus, it seems that tolvaptan is an advancement in the treatment of severely decompensated HF. 相似文献
5.
《Expert review of clinical pharmacology》2013,6(5):601-612
Tolvaptan is a new vasopressin antagonist developed for the treatment of hypervolemic or euvolemic hyponatremia. It has greater affinity for the V2 receptor than native vasopressin or any other vasopressin antagonist. Blockade of the V2 receptor induces solute-free water excretion without affecting normal electrolyte excretion. The pharmacokinetics and pharmacodynamics of tolvaptan are suitable for once-daily dosing. Throughout all phases of clinical studies, it was shown to be safe for short- and long-term use. Tolvaptan effectively increases serum sodium levels in patients with heart failure, cirrhosis and syndrome of inappropriate secretion of antidiuretic hormone. In patients hospitalized owing to heart failure, tolvaptan decreased bodyweight, increased urine output and improved dyspnea compared with placebo. However, tolvaptan has not proven to be beneficial for the long-term management of heart failure. Currently, tolvaptan is the only oral agent in its class available in the USA and Europe. 相似文献
6.
INTRODUCTION: It has been > 25 years since it was first discovered that arginine vasopressin levels are elevated in heart failure and this elevation is proportional to the severity of heart failure. Tolvaptan is an oral nonpeptide V?-selective antagonist and has been shown to induce free water excretion without increasing urine sodium, an effect termed 'aquaresis'. AREAS COVERED: This paper aims to review the physiology, chemistry, pharmacokinetics, clinical efficacy and safety of tolvaptan in HF. A PubMed literature search was performed using 'tolvaptan' and the MeSH term 'heart failure', yielding 89 references. EXPERT OPINION: Clinical trials conducted in ambulatory and hospitalized patients with HF have found treatment with tolvaptan causes rapid and sustained body weight reductions concurrent with increases in urine output, improves and/or normalizes serum sodium in hyponatremic patients, reduces signs and symptoms of congestion and increases thirst. However, tolvaptan has not been shown to decrease HF re-hospitalization or mortality. As an adjunct to standard therapy, tolvaptan is unique in that it is virtually the only novel agent tested in patients hospitalized for acute heart failure syndrome (AHFS) to reach its primary end point for short-term efficacy without causing deleterious side effects. There is theoretical concern that chronic V? receptor blockade may cause harmful long-term side effects via enhanced V(1a) receptor activation, potentially offsetting any favorable effects on congestion and hyponatremia. The 'vaptan' class of drugs is an active and promising area for clinical investigation and future research is necessary to clarify the therapeutic role of selective and nonselective vasopressin inhibition in chronic HF and AHFS. 相似文献
7.
Doggrell SA 《Expert opinion on pharmacotherapy》2004,5(10):2181-2184
Despite diuretics being used to relieve the fluid retention/congestion associated with heart failure (HF), patients with HF are commonly hospitalised due to progressive volume retention with an increase in body weight and the deterioration of symptoms. Arginine vasopressin acts at vasopressin V2 receptors in the kidney as an antidiuretic. Tolvaptan is an orally-active selective V2-receptor antagonist. In the Acute and Chronic Therapeutic Impact of a Vasopressin antagonist in Congestive Heart Failure trial of patients hospitalised with HF, tolvaptan 30 mg/day increased urine volume and induced a weight loss of 3.3 kg at discharge (placebo; 1.9 kg). In post hoc analyses, mortality was lower with tolvaptan in patients with renal impairment and severe congestion, compared to placebo. Thus, it seems that tolvaptan is an advancement in the treatment of severely decompensated HF. 相似文献
8.
Objectives
To determine the effectiveness of the heart failure screening form in teaching heart failure treatment guidelines and prompting students to evaluate patients'' medications to initiate patient education and provider intervention.Design
Between 2002 and 2009, 123 students used the heart failure screeing form during an elective cardiology advanced pharmacy practice experience (APPE). A subset of 41 students were also assessed for change in heart failure knowledge and confidence pre- and post-APPE.Assessment
A total of 1,114 heart failure patients were screened and assessed using the tool with a mean age of 71.9 ± 12.9 years. Of those, 535 (48%) patients met screening criteria and participated in heart failure education. From 2008 through 2009, there were 45 heart failure interventions with a 60% provider acceptance rate. Significant improvements were made in heart failure knowledge and in all areas of confidence at the end of the APPE for the 41 students assessed.Discussion
The heart failure screening form is an effective tool to teach evidence-based medicine and to prompt students to initiate provider intervention and patient education. Its use is associated with significant increases in knowledge and confidence in heart failure medication therapy management in fourth-year pharmacy students. 相似文献9.
Tolvaptan is a new vasopressin antagonist developed for the treatment of hypervolemic or euvolemic hyponatremia. It has greater affinity for the V(2) receptor than native vasopressin or any other vasopressin antagonist. Blockade of the V(2) receptor induces solute-free water excretion without affecting normal electrolyte excretion. The pharmacokinetics and pharmacodynamics of tolvaptan are suitable for once-daily dosing. Throughout all phases of clinical studies, it was shown to be safe for short- and long-term use. Tolvaptan effectively increases serum sodium levels in patients with heart failure, cirrhosis and syndrome of inappropriate secretion of antidiuretic hormone. In patients hospitalized owing to heart failure, tolvaptan decreased bodyweight, increased urine output and improved dyspnea compared with placebo. However, tolvaptan has not proven to be beneficial for the long-term management of heart failure. Currently, tolvaptan is the only oral agent in its class available in the USA and Europe. 相似文献
10.
Rajagopalan S Arora A Shafiq N Reddy S S Pandhi P Mittal N Malhotra S 《British journal of clinical pharmacology》2011,72(3):369-380
AIM
The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection fraction (HFREF). Studies of the various drugs given for HFNEF have revealed conflicting results. The aim of this systematic review was to determine whether there is any benefit with pharmacotherapy in HFNEF in terms of cardiac outcomes.METHODS
Electronic and printed sources were searched until August 2010 for randomized controlled clinical trials (RCTs) comparing drug therapy with placebo in HFNEF. Weighted mean difference and pooled odds ratio (OR) with 95% confidence intervals were calculated.RESULTS
A total of six RCTs including 8410 patients with a mean follow-up period of 21 months were included in the analysis. Although there were no significant differences in all cause mortality between the two groups (pooled OR 0.95, 95% CI 0.79, 1.13, P = 0.55), the subgroup analysis revealed a slight but non significant advantage with the β-adrenoceptor blocker group. There was no significant difference between the two groups in terms of cardiovascular mortality, hospitalization, worsening heart failure, ejection fraction, E : A ratio, deceleration time and E : E′ ratio.CONCLUSION
There was no significant benefit of pharmacotherapy in HFNEF. This might have been because of a lack of stringent inclusion criteria for patients in the trials and lower power of the studies. Hence trials with well defined inclusion criteria, better power, longer follow-up periods and with echocardiographic parameters as endpoints are required to shed further light on this topic. 相似文献11.
Hysek C Schmid Y Rickli A Simmler LD Donzelli M Grouzmann E Liechti ME 《British journal of pharmacology》2012,166(8):2277-2288
BACKGROUND AND PURPOSE
The use of ±3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is associated with cardiovascular complications and hyperthermia.EXPERIMENTAL APPROACH
We assessed the effects of the α1- and β-adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or placebo was administered 1 h before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, four-period crossover design.KEY RESULTS
Carvedilol reduced MDMA-induced elevations in blood pressure, heart rate and body temperature. Carvedilol did not affect the subjective effects of MDMA including MDMA-induced good drug effects, drug high, drug liking, stimulation or adverse effects. Carvedilol did not alter the plasma exposure to MDMA.CONCLUSIONS AND IMPLICATIONS
α1- and β-Adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychotropic effects. Carvedilol could be useful in the treatment of cardiovascular and hyperthermic complications associated with ecstasy use. 相似文献12.
Sanja Milutinovi?-Smiljani? Olivera ?arenac Maja Lozi?-Djuri? David Murphy Nina Japund?i?-?igon 《British journal of pharmacology》2013,169(4):900-908
Background and Purpose
It is well recognized that vasopressin modulates the neurogenic control of the circulation. Here, we report the central mechanisms by which vasopressin modulates cardiovascular response to stress induced by immobilization.Experimental Approach
Experiments were performed in conscious male Wistar rats equipped with radiotelemetric device for continuous measurement of haemodynamic parameters: systolic and diastolic BP and heart rate (HR). The functioning of the spontaneous baro-receptor reflex (BRR) was evaluated using the sequence method and the following parameters were evaluated: BRR sensitivity (BRS) and BRR effectiveness index (BEI).Key Results
Under baseline physiological conditions intracerebroventricular injection of 100 and 500 ng of selective non-peptide V1a or V1b or V2 receptor antagonist did not modify BP, HR and BRR. Rats exposed to 15 min long stress by immobilization exhibited increase of BP, HR, reduction of BRS and no change in BEI. Pretreatment of rats with V1a receptor antagonist did not modulate the BP, HR, BRS and BEI response to stress. Pretreatment of rats with V1b receptor and V2 receptor antagonist, at both doses, prevented BRR desensitization and tachycardia, but failed to modulate stress-induced hypertension.Conclusions and Implications
Vasopressin by the stimulation of central V1b- and V2-like receptors mediates stress-induced tachycardia and BRR desensitization. If these mechanisms are involved, BRR desensitization in heart failure and hypertension associated with poor outcome, they could be considered as novel targets for cardiovascular drug development. 相似文献13.
AIM
β-Blockers are commonly prescribed for stable angina and are recommended as initial therapy. However, β-blockers are contraindicated in patients with obstructive airway disease because of a risk of bronchoconstriction. Ivabradine is a specific heart rate-lowering agent that acts via If pacemaker channels in the sinoatrial node with no β-adrenoreceptor activity. Ivabradine has been recently approved for the treatment of stable angina. This study assessed the effects of repeated administration of ivabradine on lung function in patients with asthma.METHODS
In this double-blind, placebo-controlled, crossover study, 20 subjects with asthma received either oral ivabradine 10 mg b.i.d. or placebo for 4.5 days. Forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate (PEFR) were designated as the main outcome variable. Diary cards were used to monitor asthma symptoms on a five-point scale, rescue medication usage, and adverse events.RESULTS
There were no significant differences in mean variation of FEV1 (ivabradine P = 0.664; placebo P = 0.652) or PEFR (ivabradine P = 0.153; placebo P = 0.356) from baseline following administration of ivabradine. There was also no significant difference in maximum percent variation in FEV1 or PEF between treatment groups (P = 0.994; FEV1 and P = 0.704; PEF). On a similar note, there was no significant difference in asthma symptoms or rescue medication usage reported between the two groups. Adverse events were generally mild-to-moderate in intensity and no cardiovascular or serious adverse events were recorded.CONCLUSIONS
This study confirms that ivabradine does not affect respiratory function or symptoms in patients with asthma and therefore represents a valuable therapeutic alternative to β-blockers for treating patients with stable angina and asthma.WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
- Ivabradine is a new heart rate-lowering agent that acts specifically on the sinoatrial node via the If pacemaker channels.
- Ivabradine has demonstrated similar efficacy to β-blockers.
- As β-blockers are contraindicated in patients with obstructive airway disease, this study was conducted to assess the safety of ivabradine in patients with asthma.
WHAT THIS STUDY ADDS
- This study demonstrates that ivabradine has no effect on the pulmonary functions in patients with asthma and can be safely used a heart rate-lowering agent in patients with angina and coexistent airflow obstruction.
14.
Zhang Q Simoneau G Verstuyft C Drouet L Bal dit Sollier C Alvarez JC Rizzo-Padoin N Bergmann JF Becquemont L Mouly S 《British journal of clinical pharmacology》2011,71(2):232-236
AIMS
To investigate whether an interaction exists between amoxicillin/clavulanic acid (amoxiclav) and warfarin in patients treated with stable oral anticoagulant therapy.METHODS
In a double-blind, cross-over, placebo-controlled study, 12 patients on stable warfarin therapy, received a 7 day amoxiclav regimen or placebo.RESULTS
The mean maximum increase in INR observed was 0.22 ± 0.3 with amoxiclav vs. 0.24 ± 0.6 with placebo (P= 0.94). The day 7–day 1 factor II, R(–) and S(–) warfarin plasma concentrations were similar during the amoxiclav and placebo study periods (P= 0.81, P= 0.45, P= 0.75, respectively).CONCLUSION
Amoxiclav did not modify anticoagulation in patients treated with stable warfarin therapy and without infection. 相似文献15.
Susan E. Shoaf Seong Ryul Kim Patricia Bricmont Suresh Mallikaarjun 《European journal of clinical pharmacology》2012,68(12):1595-1603
Purpose
To compare the pharmacokinetics and pharmacodynamics of tolvaptan in Caucasian and Japanese healthy male subjects under fasting and non-fasting conditions.Methods
This was a single-center, parallel-group, randomized, open-label, three-period crossover trial of single oral doses of tolvaptan 30?mg under fasting and non-fasting [a high-fat, high-calorie meal (HFM) or Japanese standard meal] conditions in 25 healthy male Caucasian subjects and 24 healthy male Japanese subjects. Pharmacodynamic endpoints were urine volume and fluid balance for 0 to 24?h postdose.Results
In the fasted state, the plasma tolvaptan Cmax and AUC∞ geometric mean ratios (90 % confidence interval) were 1.105 (0.845–1.444) and 1.145 (0.843–1.554) for Japanese compared to Caucasian subjects. A HFM increased the Cmax and AUC∞ values by about 1.15-fold in both Japanese and Caucasian subjects.. Twenty-four-hour urine volumes paralleled pharmacokinetic changes, but the increases were not clinically significant. Fluid balance in the Japanese men was 1.4- to 2.0-fold more negative than that in the Caucasian men.Conclusion
Tolvaptan pharmacokinetics is not clinically significantly affected by race. Body weight is a factor that affects exposure. Tolvaptan can be administered with or without food. 相似文献16.
Egerer G Eisenlohr K Gronkowski M Burhenne J Riedel KD Mikus G 《British journal of clinical pharmacology》2010,70(6):903-907
AIMS
The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high-dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma.METHODS
Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg m−2). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment.RESULTS
Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for Cmax at the end of melphalan infusion (placebo 3431 ± 608 ng ml−1vs. aprepitant 3269 ± 660 ng ml−1). In addition, AUC and terminal elimination half-life were not changed by aprepitant. Total clearance of melphalan was 304 ± 58 ml min−1 m−2 (placebo) which was not influenced by aprepitant (288 ± 78 ml min−1 m−2).CONCLUSIONS
The administration of the NK1 receptor antagonist aprepitant 1 h before a high-dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan. 相似文献17.
Introduction:
Stable angina pectoris (SAP) is a widely prevalent disease affecting 30 000 to 40 000 per million people in Europe and the US. SAP is associated with reductions in quality of life and ability to work, and increased use of healthcare resources. Ivabradine is a drug with a unique therapeutic target, the If current of the sinus node, developed for the treatment of cardiovascular diseases including SAP. It has an exclusive heart rate reducing effect, without any negative effect on left ventricular function or coronary vasodilatation.Aims:
The aim of this paper is to review the evidence concerning the use of ivabradine in the treatment of SAP.Evidence review:
Ivabradine is an effective antianginal and antiischemic drug, not inferior to the beta blocker atenolol and the calcium channel antagonist (CCA) amlodipine. It decreases the frequency of angina attacks and increases the time to anginal symptoms during exercise. Because of its exclusive chronotropic effect, ivabradine is not associated with the typical adverse reactions associated with beta blockers or other antianginal drugs.Clinical value:
Clinical evidence shows that ivabradine is a very good antiischemic and antianginal agent, being as effective as beta blockade and CCA therapy in controlling myocardial ischemia and symptoms of stable angina. Ongoing studies will determine the potential of ivabradine to improve morbidity and mortality in coronary artery disease and heart failure. 相似文献18.
Haegeli L Brunner-La Rocca HP Wenk M Pfisterer M Drewe J Krähenbühl S 《British journal of clinical pharmacology》2007,64(6):804-809
What is already known about this subject
- Furosemide is an effective diuretic, but its absorption may be too slow to allow oral treatment in certain patients.
What this study adds
- In healthy volunteers, sublingual administration is associated with a higher Cmax, a higher bioavailability and a more accentuated initial natriuretic response than oral furosemide. Sublingual administration may offer advantages over oral administration of furosemide in certain clinical situations.
Background
In patients with decompensated heart failure, absorption of orally administered furosemide may be delayed, possibly leading to impaired pharmacodynamic effects. Sublingual administration may represent an alternative in such situations.Methods
In a crossover study including 11 healthy men, 20 mg furosemide was administered intravenously, orally and sublingually on three different days. Pharmacokinetics and pharmacodynamics were assessed from repeated blood and urine samples.Results
Compared with oral administration, sublingual administration was associated with 43% higher Cmax[difference 215 ng ml−1, 95% confidence interval (CI) 37, 392], a higher urinary recovery (8.9 vs. 7.3 mg, difference 1.6 mg, 95% CI 0.3, 2.9), an 28% higher AUC (difference 328 ng h−1 ml−1, 95% CI 24, 632) and a higher bioavailability of furosemide (59 vs. 47%, difference 12.0%, 95% CI −1.2, 25.2). Sodium excretion was higher after sublingual compared with oral administration (peak excretion rate 1.8 vs. 1.4 mmol min−1, P < 0.05), whereas urine volume did not differ significantly between the two application modes. In comparison, intravenous administration showed the expected more rapid and intense response.Conclusion
Sublingually administered furosemide tablets differ in certain kinetic and dynamic properties from identical tablets given orally. Sublingual administration of furosemide may offer therapeutic advantages in certain groups of patients. 相似文献19.
Meng-Ting Wang Chen-Yi Su Agnes L F Chan Pei-Wen Lian Hsin-Bang Leu Yu-Juei Hsu 《British journal of clinical pharmacology》2010,70(2):258-267
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. 相似文献20.
Frank Holden Mose Thomas Larsen Janni Majgaard Jensen Annebirthe Bo Hansen Jesper N?rgaard Bech Erling Bjerregaard Pedersen 《British journal of clinical pharmacology》2014,78(4):789-799