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Ciprofloxacin and qt interval

David F Lehmann, William D Eggleston, Dongliang Wang
BACKGROUND: Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (Cmax ) is used during drug development to screen out chemical entities likely to cause TdP. PURPOSE: To validate the use of the hERG IC50:Cmax ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence...
January 30, 2018: Pharmacotherapy
Charlotte Heemskerk, Evelien Woldman, Marieke Pereboom, Ruud Van der Hoeven, Aukje Mantel-Teeuwisse, Claudia Van Gemeren, Matthijs Lambertus Becker
PURPOSE: Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs the QT interval in patients with additional co-morbidities and risk factors. We also reviewed the literature on the QT prolonging effect or TdP inducing effect of ciprofloxacin. METHODS: ICU Patients who were treated with intravenous ciprofloxacin as part of their therapy were recruited...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Ahmed M Abdelrady, Sawsan A Zaitone, Noha E Farag, Manal S Fawzy, Yasser M Moustafa
Prolongation of QT interval is possible with fluoroquinolones, yet the underlying contributing factors have not been elucidated. Two widely used fluoroquinolone drugs were at the focus of this study in rats with/without acute myocardial dysfunction (AMI) induced by isoproterenol. The effects of levofloxacin and ciprofloxacin on the cardiac mRNA expression of rat Kv4.3, Kv1.2 and Nav1.5 mRNAs were determined. Administration of the two antibiotics produced dose-dependent changes in ECG parameters that were more prominent in rats with AMI than healthy rats; this was accompanied by elevations in serum lactate dehydrogenase and creatine kinase-MB...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Michael Fralick, Erin M Macdonald, Tara Gomes, Tony Antoniou, Simon Hollands, Muhammad M Mamdani, David N Juurlink
OBJECTIVE: To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death. DESIGN: Population based nested case-control study. SETTING: Ontario, Canada, from 1 April 1994 to 1 January 2012. PARTICIPANTS: Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker...
October 30, 2014: BMJ: British Medical Journal
Michael A Mancano
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: Your report will be published anonymously unless otherwise requested...
April 2014: Hospital Pharmacy
Jasjeet Bhullar, Karthika Natarajan, Suneet Shukla, Trevor J Mathias, Mariola Sadowska, Suresh V Ambudkar, Maria R Baer
The oral second-generation bis-aryl urea fms-like tyrosine kinase 3 (FLT3) inhibitor quizartinib (AC220) has favorable kinase selectivity and pharmacokinetics. It inhibits mutant and wild-type FLT3 in vivo at 0.1 and 0.5 µM, respectively, and has shown favorable activity and tolerability in phase I and II trials in acute myeloid leukemia, with QT prolongation as the dose-limiting toxicity. Co-administration with chemotherapy is planned. We characterized interactions of quizartinib with the ATP-binding cassette (ABC) proteins ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein)...
2013: PloS One
Kazuhiro Matsuo, Kaori Fujiwara, Naoki Omuro, Itsuki Kimura, Kazuko Kobayashi, Takashi Yoshio, Akira Takahara
The fluoroquinolone antibiotic ciprofloxacin has been reported to block delayed rectifier K(+) channels at much higher concentrations than those at which it exerts its bactericidal activity. In this study using the halothane-anesthetized guinea pig, we assessed whether ciprofloxacin has a proarrhythmic activity. Ciprofloxacin at a clinically relevant dose of 3 mg/kg, i.v. did not affect any electrocardiographic parameters. At 10 mg/kg, it prolonged the QT interval and the duration of the monophasic action potential of the ventricle under sinus rhythm and constant ventricular pacing (n = 6)...
2013: Journal of Pharmacological Sciences
Ralf Stahlmann, Hartmut M Lode
INTRODUCTION: Quinolones are among the most often prescribed antimicrobial agents. Some types of toxicity observed during therapy with these drugs have gained much attention. AREAS COVERED: Here, we review the potential of the most widely used fluoroquinolones, ciprofloxacin, levofloxacin and moxifloxacin for adverse reactions. The rates of adverse events are similar for quinolones and other antibacterial agents. However, quinolone therapy can be associated with specific risks, which must be weighed against their benefit...
July 2013: Expert Opinion on Drug Safety
P-J Guns, D M Johnson, E Weltens, J Lissens
INTRODUCTION: Assessment of the propensity of novel drugs to cause proarrhythmia is essential in the drug development process. It is increasingly recognized, however, that QT prolongation alone is an imperfect surrogate marker for Torsades de Pointes (TdP) arrhythmia prediction. In the present study we investigated the behavior of a novel surrogate marker for TdP, the electro-mechanical (E-M) window, prior to triggering of TdP episodes with sympathetic stimulation after administration of a number of reference compounds...
September 2012: Journal of Pharmacological and Toxicological Methods
Alexandros Briasoulis, Vikram Agarwal, Walter J Pierce
Although very useful agents, fluoroquinolones are associated with a number of adverse events, some with considerable clinical significance. Prolongation of the QT interval, for example, is an adverse effect associated with the use of fluoroquinolones. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels, especially the rapid component of the delayed rectifier potassium current I(Kr), expressed by HERG (the human ether-a-go-go-related gene). According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (TdP)...
2011: Cardiology
P-J Guns, D M Johnson, J Van Op den Bosch, E Weltens, J Lissens
BACKGROUND AND PURPOSE: QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A negative electro-mechanical (E-M) window has recently been proposed as an alternative risk marker for TdP in a canine LQT1 model. Here, we evaluated the E-M window in anaesthetized guinea pigs as a screening marker for TdP in humans...
May 2012: British Journal of Pharmacology
Morhaf Ibrahim, Bassam Omar
A 65-year-old man with recently diagnosed urinary tract infection treated with ciprofloxacin (Cipro) presented to our institution with recurrent seizure-like activity. His rhythm revealed torsade de pointes, which required defibrillation. Subsequent electrocardiogram revealed severely prolonged QT interval, which near-completely resolved 7 days later off Cipro. This case highlights a rare but potentially fatal side effect of quinolone antibiotics, especially in combination with other QT-prolonging medications...
January 2012: American Journal of Emergency Medicine
Ralf Stahlmann, Hartmut Lode
The fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin and gemifloxacin are widely used for the treatment of various types of bacterial infections. Overall, these antibacterial agents can be considered safe and well tolerated drugs. Comparative studies have evaluated the use of quinolones in elderly and younger populations. Although age per se does not seem to decrease their tolerability, specific adverse effects of the quinolones must be considered when they are chosen for antibacterial treatment. Renal function declines consistently with age and doses of renally excreted quinolones (e...
March 1, 2010: Drugs & Aging
Masoud Selk Ghaffari, Reza Parsamehr
The purpose of this study was to evaluate the electrocardiographic effects of single intravenous dose of ciprofloxacin in dogs. Ten adult cross-breed dogs of both sexes were selected as the sample population. Baseline electrocardiographic values were recorded just before drug administration. Then the dogs received intravenous infusion of ciprofloxacin (10 mg/kg) over the fifteen minutes. The ECGs recorded at 15, 30, 60 and 120 minutes after ciprofloxacin administration. The ECG measurements of heart rate, PR interval, QRS interval, ST segment, T-wave amplitude and QT interval were taken from lead II...
December 2009: Veterinary Research Communications
Murali K Nair, Krunal Patel, Perry J Starer
ABSTRACT Background Methadone has been associated with QT prolongation and Torsades de pointes. Ciprofloxacin may prolong QT interval and induce Torsades de pointes when other risk factors are present. Case description A case is described in which a patient receiving methadone treatment developed Torsades de pointes following the addition of ciprofloxacin. Conclusion Ciprofloxacin should be used with caution in patients receiving methadone.
December 2008: Addiction
Anastasia Keivanidou, Christos Arnaoutoglou, Argyrios Krommydas, Georgios Papanikolaou, Konstantinos Tsiptses, Charalampos Chrisopoulos, Christos Kirpizidis
We report one case of cardiac arrest related to ciprofloxacin administration. One female patient (aged 70 years old) developed a marked QTc prolongation (QTc = 0.62 s) within 24 hours of ciprofloxacin administration, with documented torsades de pointes and recurrent syncope that required defibrillation. The patient was under amiodarone and sotalol therapy for atrial fibrillation, with no obvious QT prolongation prior to ciprofloxacin therapy. QT prolongation and subsequent torsades de pointes appeared only after initiation of ciprofloxacin and normalized after drug discontinuation...
2009: Cardiology Journal
John P Knorr, Mersedeh Moshfeghi, Mary C Sokoloski
PURPOSE: A case of Q-T interval prolongation in a pediatric patient with no known risk factors for the development of a long Q-T syndrome is reported. SUMMARY: A 16-year-old boy arrived at a children's hospital reporting mucous diarrhea that had lasted two weeks, light-headedness with two blackouts on the day before his arrival to the hospital, and a 4.3-kg weight loss over the previous three weeks. He had a 3.5-year history of Crohn's disease and had been hospitalized for two months with a diagnosis of colitis with cryptitis...
March 15, 2008: American Journal of Health-system Pharmacy: AJHP
Jarosław Kaźmierczak, Małgorzata Peregud-Pogorzelska, Ryszard Rzeuski
The presented case report describes a male patient with an implanted cardioverter-defibrillator (ICD) in whom a coadministration of ciprofloxacin and azimilide caused QT interval prolongation and multiple episodes of torsades de pointes (TdP) followed by ICD shocks (arrhythmic storm). The case highlights a not described drug interaction between azimilide and ciprofloxacin, which is believed to be the safest member of fluoroquinolones class.
August 2007: Pacing and Clinical Electrophysiology: PACE
Peter Milberg, Ekkehard Hilker, Shahram Ramtin, Yilmaz Cakir, Jörg Stypmann, Markus A Engelen, Gerold Mönnig, Nani Osada, Günter Breithardt, Wilhelm Haverkamp, Lars Eckardt
BACKGROUND: Numerous noncardiovascular drugs prolong repolarization and thereby increase the risk for patients to develop life-threatening tachyarrhythmias of the torsade de pointes (TdP) type. The development of TdP is an individual, patient-specific response to a repolarization-prolonging drug, depending on the repolarization reserve. The aim of the present study was to analyze the underlying mechanisms that discriminate hearts that will develop TdP from hearts that will not develop TdP...
June 2007: Journal of Cardiovascular Electrophysiology
Matthew E Falagas, Petros I Rafailidis, Evangelos S Rosmarakis
Fluoroquinolones are widely used and well tolerated antibacterial agents. However, prolongation of the QT interval is an adverse effect associated with the use of fluoroquinolones. According to the available case reports and clinical studies, moxifloxacin carries the greatest risk of QT prolongation from all available quinolones in clinical practice and it should be used with caution in patients with predisposing factors for Torsades de pointes (Tdp). Although gemifloxacin, levofloxacin and ofloxacin are associated with a lower risk of QT prolongation compared with moxifloxacin, they should also be used with caution in patients with risk factors for QT prolongation...
April 2007: International Journal of Antimicrobial Agents
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