Author + information
- Pietro Enea Lazzerini, MD∗ (, )
- Iacopo Bertolozzi, MD,
- Marco Rossi, PharmD,
- Pier Leopoldo Capecchi, MD and
- Franco Laghi-Pasini, MD
- ↵∗Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Viale Bracci 14, 53100 Siena, Italy
We read with great interest the paper by Lorberbaum et al. (1) recently published in the Journal, in which evidence was provided that ceftriaxone plus lansoprazole combination therapy (CFX+LSZ) was unexpectedly associated with an increased risk of acquired long QT syndrome (aLQTS); thus, it is also theoretically associated with Torsades de Pointes (TdP) and sudden cardiac death. We report on 2 clinical observations that possibly further support these findings.
First, we recently observed a patient affected with pneumonia who specifically developed aLQTS after CFX+LSZ administration.
On admission, the patient’s electrocardiogram (ECG) showed a normal corrected QT interval (QTc; 422 ms). Ceftriaxone administration was started (2 g/day), and a second ECG performed 3 days later did not reveal any significant change in the QTc (417 ms). On day 8, the patient reported epigastralgia, and lansoprazole (30 mg/day) was added to therapy. After 2 days of the combined treatment, QTc prolongation developed (475 ms), despite no changes in electrolytes, echocardiography findings, or further drug use. Lansoprazole was stopped and replaced with pantoprazole, whereas ceftriaxone was continued. Two days later, QTc normalized with restoration of baseline values (424 ms).
Second, in a cohort of unselected TdP patients, we observed that CFX+LSZ was assumed by a non-negligible percentage of subjects.
Since 2008, we have prospectively recruited patients who experienced TdP, independent of ongoing therapies and concomitant diseases. To date, 40 consecutive patients have been recruited. As expected (2), a high prevalence of recognized QT-prolonging factors of acquired origin were present (on average >4), including mainly cardiac diseases (82%), electrolyte imbalances (70%), QT-prolonging medications (57%, globally considered), and anti-Ro/Sjogren's syndrome-related antigen A antibodies (52%) (3).
In this cohort, we found that 2 patients (5%) were receiving CFX+LSZ when TdP developed. Notably, this percentage was identical to that observed with levofloxacin, clarithromycin, or promazine (5% each) and was higher than that seen with ciprofloxacin, sotalol, or haloperidol (2%), which all represent well-recognized QT-prolonging medications (4). Only amiodarone (27%) and citalopram, fluconazole, or sertraline (7%) were more frequently administered.
Although follow-up studies are required to confirm the findings of Lorberbaum et al. (1), our observations seem to be in agreement with the view that CFX+LSZ may represent a currently overlooked contributing factor that increases the TdP risk, via specific (not class-related) QT-prolonging effects exerted by these 2 molecules when combined.
The potential harmfulness of this association should be carefully kept in mind, particularly in the presence of other recognized QT-prolonging factors. Both drugs are used worldwide, but they are presently considered as having neutral effects on ventricular repolarization.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
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- ↵Woosley RL, Romero KA. Crediblemeds.org QT drugs List, 2016. AZCERT, Inc. Available at: https://crediblemeds.org. Accessed October 18, 2016.