Dextropropoxyphene effects on QTc-interval prolongation: Frequency and characteristics in relation to plasma levels

Guillermo Alberto Keller, MD, PhD; Cecilia Villa Etchegoyen, MD; Nicolás Fernandez, PharmD, PhD; Nancy Mónica Olivera, PharmD, PhD; Patricia Noemí Quiroga, PharmD, PhD; Roberto Alejandro Diez, PhD; Guillermo Di Girolamo, MD, PhD

doi:10.5055/jom.2018.0466

Authors

Guillermo Alberto Keller, MD, PhD
Cecilia Villa Etchegoyen, MD
Nicolás Fernandez, PharmD, PhD
Nancy Mónica Olivera, PharmD, PhD
Patricia Noemí Quiroga, PharmD, PhD
Roberto Alejandro Diez, PhD
Guillermo Di Girolamo, MD, PhD

DOI:

https://doi.org/10.5055/jom.2018.0466

Keywords:

dextropropoxyphene, QT-interval prolongation, torsade de pointes, arrhythmia, adverse drug reaction

Abstract

Objective: To evaluate frequency and risk factors for dextropropoxyphene-induced QT-interval prolongation in the clinical setting.

Design: Prospective, noninterventional, observational, longitudinal cohort approach. Electrocardiograms were blindly evaluated by independent professionals.

Setting: General ward of a public hospital of metropolitan Buenos Aires.

Patients, Participants: Ninety-two patients with indication of receiving dextropropoxyphene for analgesic purposes were included consecutively. All patients finished the study.

Interventions: All patients were monitored with electrocardiographic controls (previous to drug administration and during steady state) to diagnose and quantify changes in the duration of the QTc interval.

Main Outcome Measure: Frequency of drug-induced QTc interval prolongation, QTc interval correlation with plasma drug, and metabolite levels.

Results: Ninety-two patients were studied (50 percent males). All patients received a (mean ± SD [range]) dextropropoxyphene dose of 125 ± 25[100-150] mg/d. Dextropropoxyphene and norpropoxyphene concentrations were 112 ± 38[45-199] and 65 ± 33[13-129] ng/mL, respectively. The intra-treatment QTc interval was >450 ms in only one patient (only with the Hodge correction). There were no cases of QTc > 500 ms, and there were no significant differences in the results considering different correction formulas (Bazzet, Fridericia, Framingham, Hodges). Dextropropoxyphene concentrations correlated with QTc (R > 0.45) interval and ΔQTc (R 0.52-0.87), whereas norpropoxyphene correlation was even greater for QTc (R > 0.40-0.64) and ΔQTc (R > 0.47-0.92). Depending on the QTc correction formula, eight patients presented ΔQTc > 30 ms and one patient with ΔQTc > 60 ms. No patient presented arrhythmia during the study.

Conclusions: The authors did not observe a relationship between dextropropoxyphene and QTc interval prolongation at the therapeutic doses used in Argentina.

Author Biographies

Guillermo Alberto Keller, MD, PhD

Universidad de Buenos Aires, Facultad de Medicina, Departamento de Toxicología y Farmacología, Centro de Vigilancia y Seguridad de Medicamentos, Buenos Aires, Argentina; Emergency Department, Hospital General de Agudos Donación Francisco J. Santojanni, Buenos Aires, Argentina

Cecilia Villa Etchegoyen, MD

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Toxicología y Química Legal, Centro de Asesoramiento Toxicológico Analítico (CENATOXA), Buenos Aires, Argentina

Nicolás Fernandez, PharmD, PhD

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Toxicología y Química Legal, Centro de Asesoramiento Toxicológico Analítico (CENATOXA), Buenos Aires, Argentina

Nancy Mónica Olivera, PharmD, PhD

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Toxicología y Química Legal, Centro de Asesoramiento Toxicológico Analítico (CENATOXA), Buenos Aires, Argentina

Patricia Noemí Quiroga, PharmD, PhD

Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Toxicología y Química Legal, Centro de Asesoramiento Toxicológico Analítico (CENATOXA), Buenos Aires, Argentina

Roberto Alejandro Diez, PhD

Universidad de Buenos Aires, Facultad de Medicina, Departamento de Toxicología y Farmacología, Centro de Vigilancia y Seguridad de Medicamentos, Buenos Aires, Argentina

Guillermo Di Girolamo, MD, PhD

Universidad de Buenos Aires, Facultad de Medicina, Departamento de Toxicología y Farmacología, Centro de Vigilancia y Seguridad de Medicamentos e Instituto de Investigaciones Cardiológicas “Prof. Dr. Alberto C. Taquini”, Buenos Aires, Argentina

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