Torsade de pointes associated with moxifloxacin: A rare but potentially fatal adverse event

Abstract

A long QT interval, which is the surface electrocardiogram (ECG) manifestation of a prolonged repolarization phase, is associated with an increased risk of torsade de pointes (TdP). If transient, it may present with syncope, and if is not transient, it may cause sudden death. A long QT interval may be congenital or acquired. The most common cause of an acquired long QT interval is drug administration (1). The drugs that interfere with potassium influx, commonly by blocking the human ether-a-go-go-related gene channel-dependent potassium current (as with fluoroquinolones) in myocyte membranes produce a prolongation of the corrected QT (QTc) interval and increase the risk of spontaneous arrhythmia generation (2). Fluoroquinolones have been reported to prolong the QTc interval and precipitate TdP in patients at high risk (1,3). We present a patient with bradycardia who developed TdP during oral moxifloxacin therapy for pneumonia. CASE PRESENTATIONAn 87-year-old woman with hypertension, chronic renal failure and dementia was admitted to the emergency department with presyncope. Junctional rhythm with a rate of 30/min was present on ECG, and the QT interval was 0.66 s; the QTc interval, according to Bazett's formula, was 0.47 s (Figure 1). There were no previous ECGs performed. Medications she was using at the time of admission included ginkgo glycosides (19.2 mg/day), valsartan 80 mg plus hydrochlorothiazide (12.5 mg/day), acetylsalicylic acid (100 mg/day) and citalopram (20 mg/day). Her serum creatinine level was 283 μmol/L and potassium level was 4.2 mmol/L at admission. Other biochemical tests were normal. A temporary transvenous cardiac pacemaker was implanted and set to a rate of 60 beats/min. The pacemaker was turned off 24 h after the implantation because sinus rhythm resumed, but it was left in place in case of bradycardia. On that day, 400 mg/day oral moxifloxacin was prescribed to the patient for aspiration pneumonia. At the beginning of moxifloxacin treatment, the rhythm was normal, with normal QT (0.40 s) and QTc (0.43 s) intervals at a heart rate of 68 beats/min. The patient was transferred to the intensive care unit for telemetric follow-up due to the possible recurrence of symptomatic bradycardia. Intermittant junctional rhythms were observed on the monitor, but sinus rhythm was dominant. On the fourth day of moxifloxacin therapy, TdP developed following a short-long-short sequence of junctional rhythm (Figure 2) and recovered spontaneously after 36 s. The QT interval on the ECG taken on the same Torsade de pointes occuring due to a long QT interval is a rare but potentially fatal arrhythmia. Acquired long QT develops most commonly because of drugs that prolong ventricular repolarization. It has been reported that fluoroquinolone antimicrobials prolong the corrected QT interval but rarely cause torsade de pointes. A patient with torsade de pointes risk factors (female sex, advanced age, extreme bradycardia and renal failure) who developed the condition on the fourth day of 400 mg/day of oral moxifloxa...

Drug-Induced Long QT Syndrome

“…Indeed, there have been case reports of TdP with moxifloxacin (Altin et al, 2007;Dale et al, 2007;Sherazi et al, 2008). Thus, it is entirely possible that potentially useful drugs have therefore been abandoned based on the possibility of a DRUG-INDUCED LONG QT SYNDROME severe adverse drug event occurring in literally one in a million exposed subjects, emphasizing the risk-benefit calculus inherent in prescribing any drug, and the unrealistic goal of guaranteeing no risk with drug therapy.…”

Cardiovascular and metabolic safety profiles of the fluoroquinolones

“…In fact, the clinical burden of fluoroquinolones-related CV diseases is strictly related to the co-existent morbidities and pharmacotherapy. As shown by case reports and series, the presence of chronic heart and/or kidney failure, history of cardiomyopathy, rhythm disorders and electrolyte imbalance, use of amiodarone, sotalol, b-blockers and/or digitalis might have exacerbated the risk of TdP [31-33,35-41, [43][44][45][46][47][48][49][50][51][52]. Accordingly, all these covariates had been also taken into account during pharmacovigilance studies [67], which offer a more reliable picture of the 'real' use of these drugs.…”

The Future for Early-Stage Tuberculosis Drug Discovery

“…Disruption of this channel leads to an increased QT interval which can trigger Torsades de pointes (TdP) arrhythmia and sudden death [75,76]. Current drugs under development, as well as new agents for TB seem to be particularly prone to this potential side effect.…”

“…Current drugs under development, as well as new agents for TB seem to be particularly prone to this potential side effect. For example, clinical doses of fluoroquinolones, such as moxifloxacin and levofloxacin, have been associated with prolonged QT via hERG blockage [75–78]. This blockage has been attributed to the protonated carboxylic acid moiety present on all fluoroquinolones [79,80].…”