Postmarketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and food and drug administration regulatory actions

Wysowski, Diane K.; Corken, A.; Gallo-Torres, Hugo E.; Talarico, Lilia; Rodriguez, Evelyn M.

doi:10.1111/j.1572-0241.2001.03927.x

Cited by 221 publications

(72 citation statements)

References 23 publications

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“…To increase gastric emptying, we used erythromycin, an antibiotic that is also an agonist of motilin and has been used to increase gastric empyting in patients with delayed gastric emptying due to gastroparesis in diabetes mellitus or postsurgical states [9]. We chose not to use cisapride due to its association with QT prolongation [10]. Additional aims of the study were to replicate previous findings regarding postprandial gastric emptying and CCK release in individuals with BN, and to examine postprandial release patterns of peptide YY (PYY) and ghrelin, appetitive hormones that have received relatively little study in these individuals [11,12].…”

Section: Introductionmentioning

confidence: 99%

Gastric emptying and symptoms of bulimia nervosa: Effect of a prokinetic agent

Devlin

Kissileff

Zimmerli

et al. 2012

Physiology & Behavior

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Objective Previous studies have suggested that delayed gastric emptying and abnormal postprandial release of hormones that influence satiation, particularly cholecystokinin (CCK), may play an important role in the pathophysiology of bulimia nervosa (BN). This study was designed to test these hypotheses as well as the efficacy of the prokinetic agent erythromycin in patients with BN. Method Thirty-two normal weight women with BN and 24 control participants consumed a large liquid test meal. Gastric emptying and pre- and postprandial release of CCK, peptide YY (PYY), and ghrelin were determined. Participants with BN were then recruited for double-blind treatment with erythromycin up to 500 mg three times daily vs. placebo for six weeks, following which they consumed a repeat test meal with gastric emptying and appetitive hormone measurements. Results CCK release at 15 minutes following the meal was marginally lower(p = 0.1) in BN than in control participants. Rate of gastric emptying and postprandial hormone release were similar in BN and controls. BN patients assigned to erythromycin compared to those assigned to placebo had more rapid gastric emptying following treatment, but there were no differences in release of CCK, PYY, or ghrelin following the post-treatment test meal. Moreover, treatment with erythromycin was not associated with clinical response. Discussion The current study does not support the clinical utility of moderate dose erythromycin in treating BN. Furthermore, the findings suggest that a modest increase in gastric emptying rate is associated neither with altered postprandial hormonal release nor with clinical benefit in these patients. While providing no evidence for the effectiveness of prokinetic agents in this setting, our findings do not preclude the possibility that a greater increase in gastric emptying rate might prove beneficial.

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Section: Introductionmentioning

confidence: 99%

Gastric emptying and symptoms of bulimia nervosa: Effect of a prokinetic agent

Devlin

Kissileff

Zimmerli

et al. 2012

Physiology & Behavior

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“…Rates of MI have increased over the last century and are attributable to lifestyle risk factors, including smoking, obesity, exercise and diet [3], [4], [5]. While non-cardiovascular target drugs such as fenfluramine, dexfenfluramine, terfanadine and cisapride have been shown to be risk factors for cardiovascular events [6], [7], [8], their effects are rare and are not considered as contributors to long term trends in morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

The Tell-Tale Heart: Population-Based Surveillance Reveals an Association of Rofecoxib and Celecoxib with Myocardial Infarction

et al. 2007

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BackgroundCOX-2 selective inhibitors are associated with myocardial infarction (MI). We sought to determine whether population health monitoring would have revealed the effect of COX-2 inhibitors on population-level patterns of MI.Methodology/Principal FindingsWe conducted a retrospective study of inpatients at two Boston hospitals, from January 1997 to March 2006. There was a population-level rise in the rate of MI that reached 52.0 MI-related hospitalizations per 100,000 (a two standard deviation exceedence) in January of 2000, eight months after the introduction of rofecoxib and one year after celecoxib. The exceedence vanished within one month of the withdrawal of rofecoxib. Trends in inpatient stay due to MI were tightly coupled to the rise and fall of prescriptions of COX-2 inhibitors, with an 18.5% increase in inpatient stays for MI when both rofecoxib and celecoxib were on the market (P<0.001). For every million prescriptions of rofecoxib and celecoxib, there was a 0.5% increase in MI (95%CI 0.1 to 0.9) explaining 50.3% of the deviance in yearly variation of MI-related hospitalizations. There was a negative association between mean age at MI and volume of prescriptions for celecoxib and rofecoxib (Spearman correlation, −0.67, P<0.05).Conclusions/SignificanceThe strong relationship between prescribing and outcome time series supports a population-level impact of COX-2 inhibitors on MI incidence. Further, mean age at MI appears to have been lowered by use of these medications. Use of a population monitoring approach as an adjunct to pharmacovigilence methods might have helped confirm the suspected association, providing earlier support for the market withdrawal of rofecoxib.

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“…In 2000, cisapride, an effective prokinetic agent, was removed from the market due to cardiac side effects (36,37). Metoclopramide use increased significantly shortly after this, likely reflecting the therapeutic hole left by the withdrawal of cisapride (38).…”

Section: Discussionmentioning

confidence: 99%

Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants

Ericson

Arnold

Cheeseman

et al. 2015

J. pediatr. gastroenterol. nutr.

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Objective Prokinetic medications are used in premature infants to promote motility and decrease time to full enteral feeding. Erythromycin and metoclopramide are the most commonly used prokinetic medications in the neonatal intensive care unit (NICU), but their safety profile is not well defined. Methods We conducted a large retrospective cohort study using data from 348 NICUs managed by the Pediatrix Medical Group. All infants exposed to ≥1 dose of erythromycin, metoclopramide, or both, from a cohort of 887,910 infants discharged between 1997 and 2012 were included. We collected laboratory and clinical information while infants were exposed to erythromycin or metoclopramide and described the frequency of laboratory abnormalities and clinical adverse events. Results Metoclopramide use increased from 1997–2005 and decreased from 2005–2012, while erythromycin use remained stable. Erythromycin use was most often associated with a diagnosis of feeding problem (40%), while metoclopramide was most often associated with a diagnosis of gastroesophageal reflux (59%). The most common laboratory adverse event during exposure to erythromycin or metoclopramide was hyperkalemia (8.6/1000 infant days on erythromycin and 11.0/1000 infant days on metoclopramide). Incidence of pyloric stenosis was greater with erythromycin than with metoclopramide (10/1095, 0.9% vs. 76/19,001, 0.4%, p=0.01), but odds were not significantly increased after adjusting for covariates (odds ratio=0.52 [95% CI: 0.26, 1.02], p=0.06). More infants experienced an adverse event while treated with metoclopramide than with erythromycin (odds ratio=1.21 [95% CI: 1.03, 1.43]). Conclusion Metoclopramide was associated with increased risk of adverse events compared to erythromycin. Studies are needed to confirm safety and effectiveness of both drugs in infants.

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Postmarketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and food and drug administration regulatory actions

Cited by 221 publications

References 23 publications

Gastric emptying and symptoms of bulimia nervosa: Effect of a prokinetic agent

Gastric emptying and symptoms of bulimia nervosa: Effect of a prokinetic agent

The Tell-Tale Heart: Population-Based Surveillance Reveals an Association of Rofecoxib and Celecoxib with Myocardial Infarction

Use and Safety of Erythromycin and Metoclopramide in Hospitalized Infants

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