The influence of cisapride and clarithromycin on QT intervals in healthy volunteers (original) (raw)
Related papers
QT prolongation and torsades de pointes associated with concurrent use of cisapride and erythromycin
American Journal of Otolaryngology, 2002
Prolongation of QT interval may lead to serious, potentially life-threatening, ventricular tachyarrhythmia, such as torsades de pointes. The cause may be an inherited or an acquired malfunction of ion channels at the myocardial cell membrane. Metabolic abnormalities, starvation, nervous system injury, and drug administration cause the much more frequent acquired long QT syndrome (LQTS). Types Ia and III antiarrhythmic drugs account for the majority of these life-threatening events, whereas a number of drugs widely used in otolaryngology, such as antibiotics and antihistamines, have been recently implicated. A case of a life-threatening ventricular tachyarrhythmia after the concurrent administration of cisapride and erythromycin is presented. Reviewed are drugs commonly prescribed in otolaryngology, as well as the associated risk factors that potentially lead to LQTS. (Am J Otolaryngol 2002;23:303-307.
Cisapride and ventricular arrhythmia
British Journal of Clinical Pharmacology, 2008
• Case reports have linked cisapride to ventricular arrhythmia and sudden cardiac death. • However, two prior epidemiological studies have failed to show an association between cisapride and serious arrhythmia.
Clarithromycin, QTc interval prolongation and torsades de pointes: the need to study case reports
Therapeutic advances in infectious disease, 2013
Background: The manufacturers of clarithromycin sought a drug similar in efficacy to erythromycin but with a superior side-effect profile. They generally achieved this outcome, but postmarketing findings identified a series of reports linking clarithromycin to QTc interval prolongation and torsades de pointes (TdP) ultimately leading to a Black Box Warning. We sought to clarify risk factors associated with TdP among case reports of patients receiving clarithromycin linked to QTc interval prolongation and TdP. Methods and results: In a detailed literature search, we found 15 women, five men, and one boy meeting our search criteria. Among the 17 adults with reported clarithromycin dose and concurrent QTc interval measurement, we found no statistically significant relationship between clarithromycin dose and QTc interval duration. This did not change for the adults who developed TdP. Among adults, major risk factors were female sex (15), old age (11) and heart disease (17). A total of eight adult subjects had all three major risk factors and 14 of the 20 adults had at least two major risk factors. All adult subjects had at least two risk factors besides clarithromycin. A total of four of the 20 adults received cisapride and three received disopyramide. Three adults were considered to suffer from some aspect of the congenital long QT syndrome. Conclusions: We believe that the risk factor description for this drug should be refined to emphasize the major risk factors of (1) female sex, (2) old age and (3) heart disease.
American Journal of Gastroenterology, 2001
OBJECTIVE:To describe the postmarketing safety data used in the risk assessment of cisapride and to summarize the regulatory actions of the Food and Drug Administration (FDA).METHODS:The FDA analyzed reports of patients who developed QT prolongation, torsades de pointes, and ventricular arrhythmia in association with the use of cisapride to assess probable etiology and risk factors.RESULTS:While cisapride was being marketed from 1993–1999, the FDA received reports of the following patients: 117 who developed QT prolongation; 107, torsades de pointes; 16, polymorphic ventricular tachycardia; 18, ventricular fibrillation; 27, ventricular tachycardia; 25, cardiac arrest; 16, serious (unspecified) arrhythmia; and 15, sudden death; for a total of 341 individual patients affected, following use of cisapride. Eighty (23%) of the 341 patients died. Deaths were directly or indirectly associated with an arrhythmic event. Factors that suggested an association with cisapride included a temporal relationship between use of cisapride and arrhythmia, the absence of identified risk factors and other explanations for arrhythmia in some patients, and cases of positive dechallenge and rechallenge. In most individuals, the arrhythmia occurred in the presence of risk factors (other drugs and/or medical conditions).CONCLUSIONS:Postmarketing reports and pharmacokinetic and electrophysiological data provided evidence that cisapride is associated with the occurrence of QT prolongation and torsades de pointes. The risk of fatal arrhythmia with cisapride was believed to outweigh the benefit for the approved indication, treatment of nocturnal heartburn due to gastroesophageal reflux disease, leading to the drug’s discontinuation in the United States.
Cisapride-induced long QT interval
The Journal of Pediatrics, 1996
A 2-month-old infant with gastroesophageal reflux was treated with cisapride. Bradycardia developed and an electrocardiogram revealed 2: I atrioventricular conduction and a prolonged QT interval. After cessation of cisapride therapy, both the rhythm and the QT interval returned to normal. Prolonged QT interval during treatment with cisapride may occur in children as in adults. (J PEDIATR 1996;128:279-81)
Prolongation of the QT interval related to cisapride-diltiazem interaction
Pharmacotherapy
Cisapride, a cytochrome P450 3A4 (CYP3A4) substrate, is widely prescribed for the treatment of gastrointestinal motility disorders. Prolongation of QT interval, torsades de pointes, and sudden cardiac death have been reported after concomitant administration with erythromycin or azole antifungal agents, but not with other CYP3A4 inhibitors. A possible drug interaction occurred in a 45-year-old woman who was taking cisapride for gastroesophageal reflux disorder and diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. The patient was in near syncope and had QT-interval prolongation. After discontinuing cisapride, the QT interval returned to normal and symptoms did not recur. We suggest that caution be taken when cisapride is prescribed with any potent inhibitor of CYP3A4, including diltiazem.
Effects of Cisapride on QTc Interval in Children
2008
Objective: Cisapride is a prokinetic drug with different reports on its cardiac side effects. As there might be a genetic susceptibility for the effects of this drug, we studied its effects on QTc interval of children in our region. Material & Methods: This semi-experimental study was performed on children aged over one month, who attended Amirkola Children's Hospital from October 2004 to March 2005 and needed to be treated with Cisapride. Patients with risk factors such as cardiac disease, electrolyte disturbance and drug usage interfering with Cisapride metabolism were excluded from the study. Cisapride was prescribed orally 0.6mg/kg/day in 3 doses. ECG was taken in lead II before drug administration and after one week. QTc intervals before and after treatment were compared. P-value >0.05 was considered significant. Findings: Among 135 admitted children needing Cisapride, 118 cases fulfilled inclusion criteria and were enrolled in the study. Their mean age was 14.1 (1.5) months. The mean QTc intervals before and after treatment were 377 (20) msec and 380 (22) msec, respectively (P=0.1). No child had a QTc interval more than 450 msec. Conclusion: Cisapride (0.6mg/kg/day) did not cause a significant prolonged QTc interval in children with no risk factor.
Effects of Cisapride on QT Interval in Children
Clinical Pediatrics, 1999
Recent reports of torsade de pointes and heart block associated with prolonged QT interval in children receiving cisapride raise questions about its safety. We prospectively examined the effects of cisapride on the QT interval in children. Electrocardiography was performed on 30 children before and after cisapride was administered. An additional 71 children underwent electrocardiography only after starting cisapride. The incidence of a corrected QT (QTc) interval > 440 msec or a marked abnormality in T wave morphology was determined in all 101 children. Cisapride significantly lengthened the QTc with a mean increase of 15.5 +/- 4.6 msec (mean +/- SEM, p = 0.002 in the 30 children with baseline electrocardiographs. Twelve of the 101 patients were found to have a QTc > 440 msec, and one had a new prominent notched T wave in all leads. In these 13 (13%) patients with repolarization abnormalities, other factors that might contribute to a long QT were noted in 11 (85%) patients. We conclude that cisapride use in children is associated with a modest increase in QT interval. The incidence of QTc > 440 msec is low. Most children with long QTc have other factors that could compound the effects of cisapride.
Turkish Journal of Clinics and Laboratory, 2019
Aim: Clarithromycin is a widely used macrolide antibiotic with arrhythmic effects causing torsade de pointes by elongating QT interval. Clarithromycin was used to treat acute coronary syndrome. we aimed to determine the acute effects of short-term clarithromycin treatment on novel ECG parameters in patients with acute coronary syndrome.Material and Methods: The study we conducted in 2002 evaluated the effects of clarithromycin on endothelial functions and QTdispersion. We recently analyzed these patients’ ECGs performed before and one week after of 1000 mg/day clarithromycin treatment. We analyzed newly recognized parameters; Tp–e interval, Tp-e/QTc ratio, maximum QTc, minimum QTc, QTc dispersion values, P-maximum, P-minimum and P-wave dispersion to indicate the risk of atrial and ventricular arrhythmias. Results: There were 40 patients included where 20 were treated with clarithromycin and 20 not. In the clarithromycin group, mean age of the patients was 53.2±8.0 and in control gro...