Analysis of reports of otoxicity, with symptoms of tinnitus, in the database of the Spanish Pharmacovigilance System for medicinal products for human use
e202012154
Keywords:
Ototoxicity, Tinnitus, Adverse drug reaction, PharmacovigilanceAbstract
Background: One of the adverse drug reactions (ADR) can be the Ototoxicity, either in a cochlear level or in a vestibular one. This may cause an incapacitating symptomatology due to a hearing impairment or deafness, tinnitus, or a vertiginous syndrome. The objective of this work was to analyze the notifications of ototoxic ADRs registered in the FEDRA database of the Spanish Pharmacovigilance System for Medicinal products for Human Use (SEFV-H), manifested as tinnitus, describing epidemiological and prognostic factors, as well as active principles and associated therapeutic groups.
Methods: An observational retrospective study based on the incoming registers in the FEDRA database of the SEFV-H, with tinnitus symptomatology due to ototoxicity between 1984 and 2017 has been carried out. SPSS v.20.0 program has been used for the descriptive and inferential statistics searching elements related to the emergence, seriousness or recuperation of the tinnitus.
Results: A total of 662 patients notifications were obtained with 899 suspected drugs. 64% of the patients were women. The average age was 55.8 years old. An 8.5% of the tinnitus were classified as serious, meaning a significant and persistent disability. Evaluating the causality through the modified Karch-Lasagna algorithm (SEFV-H algorithm), a causal group credible or well defined, was discovered in 48.6%. In the ATC ranking, the most frequent group of cause drugs was the N, nervous system. It was concluded, among others, that the seriousness is more significant in men and that the elder group have a great influence in the tinnitus recovery.
Conclusions: The appearance of tinnitus brought on by medical ototoxicity may determine an important limitation on the patient. A vestibular and cochlear function monitoring must be carried out on patients under treatment with high ototoxicity drugs. The task of the pharmacovigilance seems to be essential, by spreading its results and stimulating the ADR notifications in order to identify pharmacological threats.
Downloads
References
de Cos MA, Florez J. Reacciones adversas a los medicamentos. En: Florez J, Armijo JA, Mediavilla A. editors. Farmacología humana. 3º edición. Barcelona: Masson, 1997; p. 115-164.
Ley 29/2006, de 26 de julio, de garantías y uso racional de los medicamentos y productos sanitarios. BOE, 27 de julio de 2007.
McGavock H. Prescription-related illness -a scandalous pandemic. J Eval Clin Pract. 2004; 10:491-7.
Palomar Garcia V, Abdulghani Martinez F, Bodet Agusti E, Andreu Mencia L, Palomar Asenjo V. Drug-induced ototoxicity: current status. Acta Otolaryngol. 2001; 121: 569-572.
Verdel BM, Van Puijenbroek EP, Souverein PC. Drug-related nephrotoxic and ototoxic reactions: a link through a predictive mechanistic commonality. Drug Safety. 2008; 31:877-884.
Mick P, Westerberg BD. Sensorineural hearing loss as a probable serious adverse drug reaction associated with low-dose oral azithromycin. J Otolaryngol. 2007; 36: 257-263.
Ganesan P, Schmiedge J, Manchaiah V, Swapna S, Dhandayutham S, Kothandaraman PP. Ototoxicity: A Challenge in Diagnosis and Treatment. J Audiol Otol. 2018;22(2):59-68.
Verdel BM, Van Puijenbroek EP, Souverein PC. Drug-related nephrotoxic and ototoxic reactions: a link through a predictive mechanistic commonality. Drug Safety. 2008; 31:877-884.
Ruhl D, Du TT, Wagner EL, Hwan Choi J, Li S, Reed R et al. Necroptosis and apoptosis contribute to cisplatin and aminoglycoside ototoxicity. J Neurosci. 2019; 1384-18.
Rybak LP, Whitworth CA, Mukherjea D, Ramkumar V. Mechanisms of cisplatin- induced ototoxicity and prevention. Hear Res. 2007; 226: 157–167.
Real Decreto 1344/2007, de 11 de octubre, por el que se regula la Farmacovigilancia de Medicamentos de Uso Humano. BOE, 1 de noviembre de 2006.
Buenas Prácticas de Farmacovigilancia del Sistema Español de Farmacovigilancia de medicamentos de uso humano. Madrid: Ministerio de Sanidad y Consumo; 2002.
WHO Collaborating Centre for Drug Statistics Methodology, Guidelines for ATC classification and DDD assignment 2020. Oslo, Norway, 2019.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use topic E 2 A: Clinical safety data management: Definitions and standards for expedited reporting – Step 5. Note for guidance on clinical safety data management: Definitions and standards For expedited reporting, 1995. Disponible en: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use_en-15.pdf
Aguirre C, García M. Evaluación de la causalidad en las comunicaciones de reacciones adversas a medicamentos. Algoritmo del Sistema Español de Farmacovigilancia. Med Clin (Barc). 2016;147(10):461-464.
Barbieri MA, Cicala G, Cutroneo PM, Mocciaro E, Sottosanti L, Freni F et al. Ototoxic Adverse Drug Reactions: A Disproportionality Analysis Using the Italian Spontaneous Reporting Database. Front Pharmacol. 2019;10:1161.
Jourde-Chiche N, Mancini J, Dagher N, Taugourdeau S, Thomas G, Brunet C et al. Antimalarial ototoxicity: an underdiagnosed complication? A study of spontaneous reports to the French Pharmacovigilance Network. Ann Rheum Dis. 2012; 71:1586–1587.
Sagwa EL, Souverein PC, Ribeiro I, Leufkens HGM, MantelTeeuwisse AK. Differences in VigiBase® reporting of aminoglycoside suspected ototoxicity during tuberculosis treatment. Pharmacoepidemiol Drug Saf. 2017; 26:1–8.
Álvarez A, Carvajal A, Bégaud B, Moride Y, Vega T, Martín LH. Under-reporting of adverse drug reactions. Estimated based on a spontaneous reporting scheme and a sentinel system. Eur J Clin Pharmacol. 1998; 54: 483-488.
Torelló J, Castillo JR, Laínez MM, García M, Arias A. Reacciones adversas a medicamentos notificadas por los médicos de atención primaria de Andalucía. Análisis de la infranotificación. Aten Primaria. 1994; 13: 307-11.
Hazell L, Shakir SAW. Under-reporting of adverse drug reactions. Drug Saf. 2006; 29 (5): 385-396.
Mantello EB, Lupoli LM, Rodrigues PCP, Cavalcante JMS, Massuda ET, Anastasio ART. Functional Impact of Tinnitus in Patients with Hearing Loss. Int Arch Otorhinolaryngol. 2020;24(2):191-197.
Pinto PC, Sanchez TG, Tomita S. The impact of gender, age and hearing loss on tinnitus severity. Braz J Otorhinolaryngol. 2010;76(1):18-24.
Hall DA, Láinez MJ, Newman CW, Sanchez TG, Egler M, Tennigkeit F et al. Treatment options for subjective tinnitus: self reports from a sample of general practitioners and ENT physicians within Europe and the USA. BMC Health Serv Res. 2011;11:302.
Méric C, Gartner M, Collet L, Chéry-Croze S. Psychopathological profile of tinnitus sufferers: evidence concerning the relationship between tinnitus features and impact on life. Audiol Neurootol. 1998;3(4):240-52.
Unterrainer J, Greimel KV, Leibetseder M, Koler T. Experiencing tinnitus: which factors are important for perceived severity of the symptom? Int Tinnitus J. 2003;9(2):130-3.
Hiller W, Goebel G. Factors influencing tinnitus loudness and annoyance. Arch Otolaryngol Head Neck Surg. 2006;132(12):1323-9.
Yorgason JG, Fayad JN, Kalinec F. Understanding drug ototoxicity: molecular insights for prevention and clinical management. Expert Opin Drug Saf. 2006;5(3):383-99.
Cianfrone G, Pentangelo D, Cianfrone F, Mazzei F, Turchetta R, Orlando MP et al. Pharmacological drugs inducing ototoxicity, vestibular symptoms and tinnitus: a reasoned and updated guide. Eur Rev Med Pharmacol Sci. 2011;15(6):601-36.
Maru D, Malky GA. Current practice of ototoxicity management across the United Kingdom (UK). Int J Audiol. 2018;57(sup4):S76-S88.
Ruhl DS, Cable BB, Martell DW. Medication associated with hearing loss: 25 years of medical malpractice cases in the United States. Otolaryngol Head Neck Surg. 2014;151(3):431-7.
Downloads
Published
How to Cite
License
Copyright (c) 2020 María Pilar Lisbona-Alquézar, Javier Lanuza-Giménez, María Cristina Navarro-Pemán, Óscar Esteban-Jiménez, Óscar Fernández-Alquézar, Rafael Fernández-Liesa
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Usted es libre de:
Compartir — copiar y redistribuir el material en cualquier medio o formato.
La licenciante no puede revocar estas libertades en tanto usted siga los términos de la licencia.
Bajo los siguientes términos:
Atribución — Usted debe dar crédito de manera adecuada , brindar un enlace a la licencia, e indicar si se han realizado cambios. Puede hacerlo en cualquier forma razonable, pero no de forma tal que sugiera que usted o su uso tienen el apoyo de la licenciante.
NoComercial — Usted no puede hacer uso del material con propósitos comerciales.
SinDerivadas — Si remezcla, transforma o crea a partir del material, no podrá distribuir el material modificado.
No hay restricciones adicionales — No puede aplicar términos legales ni medidas tecnológicas que restrinjan legalmente a otras a hacer cualquier uso permitido por la licencia.
Avisos:
No tiene que cumplir con la licencia para elementos del material en el dominio público o cuando su uso esté permitido por una excepción o limitación aplicable.
No se dan garantías. La licencia podría no darle todos los permisos que necesita para el uso que tenga previsto. Por ejemplo, otros derechos como publicidad, privacidad, o derechos morales pueden limitar la forma en que utilice el material.
