Lansoprazole precipitated QT prolongation and torsade de pointes associated with disopyramide

Asajima, Hiroshi; Saito, Naotaka; Ohmura, Yoshinori; Ohmura, Kazue

doi:10.1007/s00228-011-1119-z

Cited by 13 publications

(7 citation statements)

References 15 publications

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“…Notably, it has been demonstrated that also lansoprazole alone significantly inhibits hERG potassium channel and related current IKr (−14%), although to a lesser extent when compared to the drug combination (−58%) (Lorberbaum et al, 2016 ). This may help explain why serum magnesium level was normal in one out of three case reports of PPI-associated TdP, in which lansoprazole administration precipitated arrhythmia development in a patients under long-term treatment with a drug known to directly prolong QTc (disopyramide) (Asajima et al, 2012 ). Thus, it cannot be ruled out that also in our patients, particularly those without hypomagnesemia, lansoprazole (and possibly also the other PPIs involved, since to date no specific patch-clamp studies are available) could have contributed to promote TdP occurrence also via a direct electrophysiological interference.…”

Section: Discussionmentioning

confidence: 99%

“…To date only three reports of patients who developed TdP while they were taking a PPI (i.e., omeprazole, pantoprazole, or lansoprazole, respectively) (Asajima et al, 2012 ; Bibawy et al, 2013 ; Hansen and Bruserud, 2016 ) have been described in the literature, in two cases associated with hypomagnesemia (Bibawy et al, 2013 ; Hansen and Bruserud, 2016 ). The results of the present study suggest that the phenomenon is significantly more common than reported, being probably underestimated because in the clinical practice PPIs do not currently receive the due attention as a factor potentially contributing to QTc prolongation and TdP.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, in 2016 the Arizona Center for Education and research on Therapeutics (AZCERT) included the PPIs omeprazole, esomeprazole, lansoprazole and pantoprazole in the list of drugs with conditional risk of TdP and to be avoided in patients with congenital LQTS (AZCERT, 2016 ), despite only few cases of QTc prolongation and TdP have been reported in patients with severe PPI-induced hypomagnesemia and/or taking a PPI concomitantly with drugs known to directly prolong QTc (Asajima et al, 2012 ; Bibawy et al, 2013 ; Hansen and Bruserud, 2016 ). As a result, it is now recommended that in patients taking a PPI for an extended period of time (>2 weeks) serum magnesium levels be monitored periodically, particularly if extended PPI therapy is used in association with drugs carrying a known risk of TdP (Asajima et al, 2012 ; 2016 ). Notably, a very recent longitudinal observational study performed in a large primary cohort of new users of acid suppression therapy followed for a median of 5.7 years, found a significant association between PPI use and risk of all-cause mortality.…”

Section: Introductionmentioning

confidence: 99%

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Proton Pump Inhibitors and Serum Magnesium Levels in Patients With Torsades de Pointes

et al. 2018

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Background: Torsades de pointes (TdP) is a life-threatening ventricular tachycardia occurring in long QT-syndrome patients. It usually develops when multiple QT-prolonging factors are concomitantly present, more frequently drugs and electrolyte imbalances. Since proton–pump inhibitors (PPIs)-associated hypomagnesemia is an increasingly recognized adverse event, PPIs were recently included in the list of drugs with conditional risk of TdP, despite only few cases of TdP in PPI users have been reported so far.Objectives: Aim of the present study is to evaluate whether PPI-induced hypomagnesemia actually has a significant clinical impact on the risk of TdP in the general population.Methods: Forty-eight unselected patients who experienced TdP were consecutively enrolled (2008-2017). Shortly after the first TdP episode, in those patients who did not receive magnesium sulfate and/or potassium or calcium replacement therapy, serum electrolytes were measured and their relationship with PPI usage analyzed.Results: Many patients (28/48, 58%) were under current PPI treatment when TdP occurred. Among TdP patients in whom serum electrolyte determinations were obtained before replacement therapy (27/48), those taking PPIs had significantly lower serum magnesium levels than those who did not. Hypomagnesemia occurred in ~40% of patients receiving PPIs (6/14), in all cases after an extended treatment (>2 weeks). In patients taking PPIs the mean QT-prolonging risk factor number was significantly higher than in those who did not, a difference which was mainly driven by lower magnesium levels.Conclusions: In unselected TdP patients, PPI-induced hypomagnesemia was common and significantly contributed to their cumulative arrhythmic risk. By providing clinical support to current recommendations, our data confirm that more awareness is needed when a PPI is prescribed, specifically as regards the risk of life-threatening arrhythmias.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proton Pump Inhibitors and Serum Magnesium Levels in Patients With Torsades de Pointes

et al. 2018

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“…In another case report, addition of lansoprazole in a patient already taking disopyramide, a class Ia antiarrhythmic agent, was associated with development of in long QT syndrome (QTc 690 ms) and TdP [ 68 ]. There has been an even more dramatic case report of pulseless ventricular tachycardia in a patient who received lansoprazole in addition to long-term therapy with voriconazole, an antifungal agent known to prolong repolarization [ 69 ].…”

Section: Main Bodymentioning

confidence: 99%

Pain medication and long QT syndrome

Klivinyi

Bornemann‐Cimenti

2018

Korean J Pain

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Long QT syndrome is a cardiac repolarization disorder and is associated with an increased risk of torsades de pointes. The acquired form is most often attributable to administration of specific medications and/or electrolyte imbalance. This review provides insights into the risk for QT prolongation associated with drugs frequently used in the treatment of chronic pain. In the field of pain medicine all the major drug classes (i.e. NSAIDs, opioids, anticonvulsive and antidepressant drugs, cannabinoids, muscle relaxants) contain agents that increase the risk of QT prolongation. Other substances, not used in the treatment of pain, such as proton pump inhibitors, antiemetics, and diuretics are also associated with long QT syndrome. When the possible benefits of therapy outweigh the associated risks, slow dose titration and electrocardiography monitoring are recommended.

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“…After 3 years, the patient was rechallenged with disopyramide without recurrence of TdP. Outside of reported clinical studies, there has been one published case report of a nonfatal TdP event with disopyramide in a patient with HCM . This patient had known QTc prolongation (570 ms) while receiving disopyramide, and the event occurred in the setting of a possible drug interaction with lansoprazole.…”

Section: Adverse Eventsmentioning

confidence: 99%

Disopyramide for Hypertrophic Cardiomyopathy: A Pragmatic Reappraisal of an Old Drug

Verlinden

Coons

2015

Pharmacotherapy

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Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by unexplained left ventricular hypertrophy in the absence of other cardiac or systemic etiologies. Approximately two-thirds of patients with HCM develop left ventricular outflow tract (LVOT) obstruction with or without provocation, whereas nearly half develop heart failure with preserved ejection fraction. Medical management of heart failure with preserved ejection fraction is based on the presence of symptoms and LVOT obstruction and frequently includes β-blockers or verapamil. Disopyramide is a class Ia antiarrhythmic that historically was used for the treatment of arrhythmias; however, its contemporary use is often reserved for patients with HCM who are persistently symptomatic despite β-blockers or verapamil and have evidence of LVOT obstruction. The pharmacologic rationale for use of disopyramide is largely based on its strong negative inotropic property. Three clinical studies have showed significant improvements in heart failure symptoms and a reduction in the need for invasive therapy in patients treated with disopyramide. Appropriate dosing and monitoring of disopyramide are important to mitigate the potential for anticholinergic adverse events and proarrhythmias. Disopyramide is a safe and effective medication that reduces heart failure symptoms and LVOT gradient and delays the need for invasive therapy in patients with obstructive HCM.

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Lansoprazole precipitated QT prolongation and torsade de pointes associated with disopyramide

Cited by 13 publications

References 15 publications

Proton Pump Inhibitors and Serum Magnesium Levels in Patients With Torsades de Pointes

Proton Pump Inhibitors and Serum Magnesium Levels in Patients With Torsades de Pointes

Pain medication and long QT syndrome

Disopyramide for Hypertrophic Cardiomyopathy: A Pragmatic Reappraisal of an Old Drug

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