Normalleft ventricular function does not protect against propafenone ...

African Journals Online (AJOL)

propafenone-induced incessant ventricular tachycardia. R. N. SCOTT MILLAR, J. B. LAWRENSON, D. A. MILNE. Abstract Propafenone is a class Ic anti-arrhythmic agent with mild B-blocking properties which has re- ..... Coplen SE, Antman EM, Berlin JA, Hewitt P, Chalmers TC. Efficacy and safery of quinidine therapy for ...

Normal left ventricular function does not protect against propafenone ...

African Journals Online (AJOL)

Normal left ventricular function does not protect against propafenone-induced incessant ventricular tachycardia. R. N. Scott Millar, J. B. Lawrenson, D.A. Milne. Abstract. Propafenone is a class Ic anti-arrhythmic agent with mild B-blocking properties which has recently become available in South Africa. We have used the ...

Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs.

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Pan, Liping; Qian, Yafang; Cheng, Minlu; Gu, Pan; He, Yanna; Xu, Xiaowen; Ding, Li

2015-01-01

This paper describes the development and validation of a liquid chromatography-mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design T max and t 1/2 of propafenone for SR-test were significantly higher than those for IR-reference while C max and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed C max and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs

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Liping Pan

2015-01-01

Full Text Available This paper describes the development and validation of a liquid chromatography–mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test, as an instant-release tablet (IR-reference and as the market leader sustained-release capsule (Rythmol, SR-reference in male beagle dogs (n=8. In Study A comparing SR-test with IR-reference in a crossover design Tmax and t1/2 of propafenone for SR-test were significantly higher than those for IR-reference while Cmax and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed Cmax and AUC of propafenone for SR-test (124.5±140.0 ng/mL and 612.0±699.2 ng·h/mL, respectively were higher than for SR-reference (78.52±72.92 ng/mL and 423.6±431.6 ng·h/mL, respectively although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.

Effect of steroid eluting versus conventional electrodes on propafenone induced rise in chronic ventricular pacing threshold.

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Cornacchia, D; Fabbri, M; Maresta, A; Nigro, P; Sorrentino, F; Puglisi, A; Ricci, R; Peraldo, C; Fazzari, M; Pistis, G

1993-12-01

The aim of this study was to evaluate chronic ventricular pacing threshold increase after oral propafenone therapy. Eighty-three patients affected by advanced atrioventricular block and sick sinus syndrome were studied at least 3 months after pacemaker implantation, before and after oral propafenone therapy (450-900 mg/day based on body weight). The patients were subdivided into three groups according to the type of unipolar electrode that was implanted: group I (41 patients) Medtronic CapSure 4003, group II (30 patients) Medtronic Target Tip 4011, and group III (12 patients) Osypka Vy screw-in lead. In all cases a Medtronic unipolar pacemaker was implanted: 30 Minix, 23 Activitrax, 14 Elite, 12 Legend, and 4 Pasys. Propafenone blood level was measured in 75 patients 3-5 hours after propafenone administration. The pacing autothreshold was measured at 0.8 V, 1.6 V, and 2.5 V by reducing pulse width. At the three different outputs before and after propafenone, threshold increments were significantly lower in group I in comparison with group II and group III (propafenone ranging from < 0.001 to < 0.05). No significant difference was found in pacing impedance or in propafenone plasma concentration in the three groups. Strength-duration curves were drawn for each group at baseline and after propafenone administration. Before propafenone, in group I, the knee was markedly shifted to the left and downward as compared to the classic curve, so that the steep part was predominant; in group II and group III this shift was progressively less evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the therapeutic effect between sodium bicarbonate and insulin on acute propafenone toxicity.

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Yi, Hwa Yeon; Lee, Jang Young; Lee, Won Suk; Sung, Won Young; Seo, Sang Won

2014-10-01

Unlike other sodium-channel-blocking antiarrhythmic agents, propafenone has β-blocking effects and calcium-channel-blocking effects. Yi et al recently studied insulin's treatment effect on acute propafenone toxicity in rats. However, because the degree of effectiveness of insulin compared to the previously known antidote sodium bicarbonate (NaHCO3) was not studied, the 2 treatment methods were compared for propafenone intoxication in rats. Rats received intravenous propafenone (36 mg/[kg h]) for 12 minutes. After the induction of toxicity, rats (n = 10 per group) received normal saline solution (NSS), NaHCO3, or insulin with glucose as treatment. Animals in the NSS, NaHCO3, and Insulin groups received an intravenous infusion of 36 mg/(kg h) propafenone until death occurred. For each animal, the mean arterial pressure (MAP, heart rate, PR interval, QRS duration, total hemoglobin, sodium, potassium, potential of hydrogen, bicarbonate, glucose, lactate, and central venous oxygen saturation (Scvo2) were measured and compared among the groups. Survival of the Insulin group was greater than that of the NSS group by log-rank test (P = .021). Sodium bicarbonate prevented the decline of MAP for 55 minutes. In comparison, insulin prevented the decline of MAP and heart rate, and the elongation of the PR interval and QRS duration for 55 minutes (P < .05). Propafenone toxicity led to decreased Ca(2+), potential of hydrogen, and Scvo2 and increased lactate levels. Insulin prevented the decrease of Ca(2+) and Scvo2, whereas NaHCO3 prevented the increase in lactate. Insulin treatment was more effective than NaHCO3 on acute propafenone toxicity in rat. Therefore, when propafenone-induced cardiotoxicity occurs, which is unresponsive to current treatment methods, glucose-insulin infusion may be considered. Copyright © 2014 Elsevier Inc. All rights reserved.

Brugada-Phenocopy Induced by Propafenone Overdose and Successful Treatment: A Case Report

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Mehmet Emre Arı

2017-10-01

Full Text Available Background: Brugada syndrome is an inherited arrhythmogenic disease that may cause sudden cardiac death due to ventricular fibrillation in young adults. Brugada syndrome caused by propafenone intoxication has been noted rarely in the literature. We report a rare case, Brugada phenocopy due to propafenone intoxication and its treatment. Case Report: A 15-year-old girl having a seizure was brought to the emergency room. She took 1.5 g propafenone (Rythmol, Abbott, Chicago, IL, USA for suicidal intention. She had metabolic acidosis. Long QRS interval and ST elevation in leads V1 through V3 were seen on electrocardiography. After bicarbonate infusion for 4 hours, haemodynamic and neurologic findings were recovered, and all electrocardiography abnormalities disappeared. The Brugada-like electrocardiography pattern was not recognized in her surface and 24-hour Holter electrocardiography at follow-up. Ajmaline challenge test was negative 2 weeks later. Conclusion: Absence of symptoms and documented ventricular tachycardia, negative challenge test, and a negative family history demonstrated that the Brugada phenocopy was a transient finding in this case and related to propafenone intoxication

POSSIBLE PREDICTORS OF ATRIAL FIBRILLATION RECURRENCE IN LONG-TERM PROPHYLACTIC PROPAFENONE THERAPY

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R. D. Kurbanov

2015-12-01

Full Text Available Aim. To identify possible predictors of atrial fibrillation (AF recurrence in 6-month prophylactic propafenone therapy. Material and methods. Patients (n=63; aged 52.2±12.6 years; 25.4% women with frequent AF recurrences who restored sinus rhythm with propafenone, were included into the study. Paroxysmal AF was observed in 84.1% of patients, and persistent AF — in 15.9% of patients. ECG, transthoracic echocardiography , chest radiography with the calculation of cardio-thoracic index (CTI was performed at baseline. All patients received rpropafenone therapy (450–600 mg/day during 6 months after sinus rhythm conversion. ECG and 24-hours ECG monitoring were performed in 1, 3 and 6 months of the therapy. Patients with 70–100% reduction in AF recurrence rate were included into the 1-st group, and patients with <70% reduction – into the 2-nd group. Results. 92%, 88.5% and 78% of patients were included into the group 1 after 1, 3 and 6 months of follow up, respectively. AF recurrences were observed 4.5, 3.8, and 1.7 times more often in women than these in men after 1, 3 and 6 months, respectively , (p>0.05. Mean age of patients in the group 2 was significantly older than this in patients of the group 1 (p<0.05. CTI, left atrium size and volume, interventricular septum thickness (IVST were significantly larger in group 2. Myocardium mass of the left ventricle (MMLV after 6 months of therapy was larger by 13.9% in patients of the group 2 vs this in patients of the group 1 (p<0.05. Conclusion. Insufficient preventive effect of propafenone was observed in 8%, 11.5% and 22% of patients in 1, 3 and 6 months of the follow-up, respectively. Propafenone prophylactic efficacy was slightly higher in men and younger patients. Patients with poor preventive effect of propafenone had a significantly larger baseline CTI, size and volume of the left atrium, IVST, and MMLV.

Lead optimization of antimalarial propafenone analogues.

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Lowes, David; Pradhan, Anupam; Iyer, Lalitha V; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W Armand; Sigal, Martina; Clark, Julie A; Wilson, Emily; Tang, Liang; Connelly, Michele C; Derisi, Joseph L; Kyle, Dennis E; Mirsalis, Jon; Guy, R Kiplin

2012-07-12

Previously reported studies identified analogues of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are nontoxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges.

[Therapy of arrhythmia induced by myocardial ischemia. Association of L-carnitine, propafenone and mexiletine].

Science.gov (United States)

Mondillo, S; Faglia, S; D'Aprile, N; Mangiacotti, L; Campolo, M A; Agricola, E; Palazzuoli, V

1995-12-01

To assess the anti-arrythmic effect of L-carnitina, propafenone and mexiletine, we tested the drugs in 50 patients with effort angina and ventricular ectopic beats (VEB). The patients were randomized in 5 groups: Group A: was treated with oral L-carnitine at the dose of 2 g x 3 for two weeks. Group B: oral propafenone at the dose of 300 mg x 3 for two weeks. Group C: as group B+L-carnitine+g x 3 at the second weeks. Group D: oral mexiletine at the dose of 200 mg x 3 for two weeks. Group E: as group D+L-carnitine 2 gr x 3 at the second week. After 7 and 14 days of treatment, in all patients an Holter examination was performed. Our results show that L-carnitine exerts a significant reduction of the VEB and its administration potentiates the anti-arrythmic effect of propafenone and mexiletine.

Lead Optimization of Anti-Malarial Propafenone Analogs

Science.gov (United States)

Lowes, David; Pradhan, Anupam; Iyer, Lalitha V.; Parman, Toufan; Gow, Jason; Zhu, Fangyi; Furimsky, Anna; Lemoff, Andrew; Guiguemde, W. Armand; Sigal, Martina; Clark, Julie A.; Wilson, Emily; Tang, Liang; Connelly, Michele C.; DeRisi, Joseph L.; Kyle, Dennis E.; Mirsalis, Jon; Guy, R. Kiplin

2015-01-01

Previously reported studies identified analogs of propafenone that had potent antimalarial activity, reduced cardiac ion channel activity, and properties that suggested the potential for clinical development for malaria. Careful examination of the bioavailability, pharmacokinetics, toxicology, and efficacy of this series of compounds using rodent models revealed orally bioavailable compounds that are non-toxic and suppress parasitemia in vivo. Although these compounds possess potential for further preclinical development, they also carry some significant challenges. PMID:22708838

Propafenone Overdose-induced Arrhythmia and Subsequent Correction After Administration of Sodium Bicarbonate

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Patrick Bruss, MD

2018-04-01

Full Text Available History of present illness: 71-year old woman presented to the emergency department with near-syncope, chest pain, and shortness of breath. She has a history of hypertension, congestive heart failure and an “irregular heartbeat.” She cannot remember what medications she takes. She recently saw her cardiologist and had some of her medications adjusted, but she can’t remember what specific changes were made. An electrocardiogram was performed, one ampule of sodium bicarbonate was administered and a repeat ECG obtained; patient felt improvement of her symptoms after administration of sodium bicarbonate. Significant findings: The first ECG in this case showed sinus tachycardia with a widened QRS (black arrow, a rightward axis, prolonged corrected QT interval (QTc, and terminal R wave in AVR (white arrow. There are several potential causes for these ECG findings, but put together with the patient’s history, we were suspicious of sodium channel blockers being the most likely cause. The second ECG, after sodium bicarbonate was administered, demonstrated a normal QRS (black arrow and no rightward axis deviation, reduction of the QTC and resolution of the terminal R wave (white arrow. We later learned that the patient’s cardiologist recently increased her propafenone dose. Discussion: Propafenone is a class 1C anti-arrhythmic that slows influx of sodium ions into the cells. It slows the rate of increase of the action potential thereby prolonging conduction and refractoriness in all areas of the myocardium.1 The mortality from acute Class 1C toxicity has been reported as high as 22.5%.1 The degree of propafenone toxicity is directly correlated to the QRS interval,1 so monitoring said interval is very helpful in determining resolution of the drug’s cardiotoxic effects. The electrocardiac effect of tricyclic antidepressants (TCAs is a well-known and often tested finding. These effects include prolongation of the QRS and QTc, right axis deviation

Effect of Propafenone on the Contractile Activity of Latissimus Dorsi Muscle Isolated in an Organ Chamber: Experimental Study in Rats

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Ricardo Simões

2002-03-01

Full Text Available OBJECTIVE: To study the effect of propafenone on the contractile function of latissimus dorsi muscle isolated from rats in an organ chamber. METHODS: We studied 20 latissimus dorsi muscles of Wistar rats and divided them into 2 groups: group I (n=10, or control group - we studied the feasibility of muscle contractility; group II (n=10, in which the contralateral muscles were grouped - we analyzed the effect of propafenone on muscle contractility. After building a muscle ring, 8 periods of sequential 2-minute baths were performed, with intervals of preprogrammed electrical stimulation using a pacemaker of 50 stimuli/min. In group II, propafenone, at the concentration of 9.8 µg/mL, was added to the bath in period 2 and withdrawn in period 4. RESULTS: In group I, no significant depression in muscle contraction occurred up to period 5 (p>0.05. In group II, a significant depression occurred in all periods, except between the last 2 periods (p0.05. CONCLUSION: Propafenone had a depressing effect on the contractile function of latissimus dorsi muscle isolated from rats and studied in an organ chamber.

Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers.

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Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Brian Houston, J; Oosterhuis, Berend; Bjerrum, Ole J; Grynkiewicz, Grzegorz; Alder, Jane; Rowland, Malcolm; Garner, Colin

2011-06-14

A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were

Exhaustive sampling of docking poses reveals binding hypotheses for propafenone type inhibitors of P-glycoprotein.

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Freya Klepsch

2011-05-01

Full Text Available Overexpression of the xenotoxin transporter P-glycoprotein (P-gp represents one major reason for the development of multidrug resistance (MDR, leading to the failure of antibiotic and cancer therapies. Inhibitors of P-gp have thus been advocated as promising candidates for overcoming the problem of MDR. However, due to lack of a high-resolution structure the concrete mode of interaction of both substrates and inhibitors is still not known. Therefore, structure-based design studies have to rely on protein homology models. In order to identify binding hypotheses for propafenone-type P-gp inhibitors, five different propafenone derivatives with known structure-activity relationship (SAR pattern were docked into homology models of the apo and the nucleotide-bound conformation of the transporter. To circumvent the uncertainty of scoring functions, we exhaustively sampled the pose space and analyzed the poses by combining information retrieved from SAR studies with common scaffold clustering. The results suggest propafenone binding at the transmembrane helices 5, 6, 7 and 8 in both models, with the amino acid residue Y307 playing a crucial role. The identified binding site in the non-energized state is overlapping with, but not identical to, known binding areas of cyclic P-gp inhibitors and verapamil. These findings support the idea of several small binding sites forming one large binding cavity. Furthermore, the binding hypotheses for both catalytic states were analyzed and showed only small differences in their protein-ligand interaction fingerprints, which indicates only small movements of the ligand during the catalytic cycle.

PROPAFENONE, A NEW EFFECTIVE ANTIARRHYTHMIC DRUG. REPORT OF 2 YEARS CLINICAL EXPERIMENT WITH PROPAFENONE (WITH BRIEF REVIEW OF ARTICLES

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IRAJ NAZERY

1986-05-01

Full Text Available Propafenone HCI (p, is a relatively new Class IC antiarrhythmic agent. It has been reported to be superior to conventional antiarrhythmics in the control of supraventricular, ventricular and WPW associated tachyarrhythmias. It has been also shown to be well tolerated. In our study protocol, which extends over 2~ years period , we used (p in 87 patients for management of various types of cardiac arrhythmias (most of whom were resistant to conventmonal antiarrhythmics . Intravenously administered, (P was effective in 85% of patients with paroxysmal reentrant supraventricular tachycardia (PRSVT, 75% of those with paroxysmal atrial fibrillation (PAF , 50% and 42% of those with refractory premature ventricular contractions (PVC and ventricular tachycardia (V. Tach, respectively. Orally administered, (P was effective in 73% of those with resistant PVCs and nonsustained ventricular tachycardia (NSV Tach, and 75% of those with resistant sustained ventricular tachycardia (RSVT •

Peginterferon Alfa-2b Injection (Sylatron)

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... Naprosyn), ondansetron (Zofran), paroxetine (Paxil, Pexeva), phenytoin (Dilantin), piroxicam (Feldene), propafenone (Rhythmol), risperidone (Risperdal), rosiglitazone (Avandia), sulfamethoxazole ( ...

Antiarrhythmic therapy and risk of death in patients with atrial fibrillation: a nationwide study

DEFF Research Database (Denmark)

Andersen, Søren Skøtt; Hansen, Morten Lock; Gislason, Gunnar H

2009-01-01

AIMS: To examine the risk of death associated with antiarrhythmic drug (AAD) therapy in a nationwide unselected cohort of patients with atrial fibrillation (AF). METHODS AND RESULTS: All patients admitted with AF in Denmark from 1995 to 2004 and their subsequent use of AADs were identified...... with flecainide, 3745 (2.6%) propafenone, 23,346 (16.5%) sotalol, and 10,376 (7.3%) amiodarone. Annualized mortality rates were 2.54, 4.25, 5.29, and 7.42 per year per 100 person years for flecainide, propafenone, sotalol, and amiodarone, respectively. Multivariable Cox proportional-hazard models did not show...

Structural basis of drugs that increase cardiac inward rectifier Kir2.1 currents.

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Gómez, Ricardo; Caballero, Ricardo; Barana, Adriana; Amorós, Irene; De Palm, Sue-Haida; Matamoros, Marcos; Núñez, Mercedes; Pérez-Hernández, Marta; Iriepa, Isabel; Tamargo, Juan; Delpón, Eva

2014-11-01

We hypothesize that some drugs, besides flecainide, increase the inward rectifier current (IK1) generated by Kir2.1 homotetramers (IKir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. To test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on Kir2.x channels. Currents were recorded with the patch-clamp technique using whole-cell, inside-out, and cell-attached configurations. Propafenone (0.1 nM-1 µM) did not modify either IK1 recorded in human right atrial myocytes or the current generated by homo- or heterotetramers of Kir2.2 and 2.3 channels recorded in transiently transfected Chinese hamster ovary cells. On the other hand, propafenone increased IKir2.1 (EC50 = 12.0 ± 3.0 nM) as a consequence of its interaction with Cys311, an effect which decreased inward rectification of the current. Propafenone significantly increased mean open time and opening frequency at all the voltages tested, resulting in a significant increase of the mean open probability of the channel. Timolol, which interacted with Cys311, was also able to increase IKir2.1. On the contrary, neither atenolol nor dronedarone modified IKir2.1. Molecular modelling of the Kir2.1-drugs interaction allowed identification of the pharmacophore of drugs that increase IKir2.1. Kir2.1 channels exhibit a binding site determined by Cys311 that is responsible for drug-induced IKir2.1 increase. Drug binding decreases channel affinity for polyamines and current rectification, and can be a mechanism of drug-induced pro- and antiarrhythmic effects not considered until now. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Assessing the Risk for Peripheral Neuropathy in Patients Treated With Dronedarone Compared With That in Other Antiarrhythmics.

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Wu, Chuntao; Tcherny-Lessenot, Stephanie; Dai, Wanju; Wang, Yunxun; Kechemir, Hayet; Gandhi, Sampada; Lin, Stephen; Juhaeri, Juhaeri

2018-03-01

There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities. The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person-years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21-1.34) compared with propafenone, to 0.94 (95% CI, 0.38-2.30) compared with sotalol. A new-user analysis showed similar results. The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.