Drug interactions detected by a computer-assisted prescription system in primary care patients in Spain: MULTIPAP study

Abstract

Background

Drug interactions increase the risk of treatment failure, intoxication, hospital admissions, consultations and mortality. Computer-assisted prescription systems can help to detect interactions.

Objectives

To describe the drug–drug interaction (DDI) and drug–disease interaction (DdI) prevalence identified by a computer-assisted prescription system in patients with multimorbidity and polypharmacy. Factors associated with clinically relevant interactions were analysed.

Methods

Observational, descriptive, cross-sectional study in primary health care centres was undertaken in Spain. The sample included 593 patients aged 65–74 years with multimorbidity and polypharmacy participating in the MULTIPAP Study, recruited from November 2016 to January 2017. Drug interactions were identified by a computer-assisted prescription system. Descriptive, bivariate, and multivariate analyses with logistic regression models and robust estimators were performed.

Results

Half (50.1% (95% CI 46.1–54.1)) of the patients had at least one relevant DDI and 23.9% (95% CI 18.9–25.6) presented with a DdI. Non-opioid–central nervous system depressant drug combinations and benzodiazepine–opioid drug combinations were the two most common clinically relevant interactions (10.8% and 5.9%, respectively). Factors associated with DDI were the use of more than 10 drugs (OR 11.86; 95% CI 6.92–20.33) and having anxiety/depressive disorder (OR 1.98; 95% CI 1.31–2.98). Protective factors against DDI were hypertension (OR 0.62; 95% CI 0.41–0.94), diabetes (OR 0.57; 95% CI 0.40–0.82), and ischaemic heart disease (OR 0.43; 95% CI 0.25–0.74).

Conclusion

Drug interactions are prevalent in patients aged 65–74 years with multimorbidity and polypharmacy. The clinically relevant DDI frequency is low. The number of prescriptions taken is the most relevant factor associated with presenting a clinically relevant DDI.

Keywords:

• Drug interactions
• polypharmacy
• multimorbidity
• primary care
• drug therapy
• computer-assisted

Acknowledgements

We thank Javier and Carlos Valilla for their help in facilitating access to the ChecktheMeds^® application. We thank our colleagues in the Research Unit for their support and all patients for their contributions to this study.

MULTIPAP group

Lead authors for the MULTIPAP Study group: Alexandra Prados Torres (Aragonese Institute of Health Sciences (IACS), IIS Aragón, Miguel Servet University Hospital, Spain) sprados. [email protected], Juan Daniel Prados Torres (Multiprofessional Teaching Unit for Family and Community Care Primary Care District Málaga-Guadarhorce. Málaga) [email protected], Isabel del Cura (Research unit. Primary Health Care Management Madrid. Spain) [email protected].

Coordinating Committee: José María Abad-Díez (Department of Health, Social Welfare and Family, Government of Aragon), Marta Alcaraz Borrajo (Subdirectorate General of Pharmacy and Health Products), Paula Ara Bardají (Aragonese Institute of Health Sciences (IACS), IIS Aragón, Miguel Servet University Hospital, Spain), Gloria Ariza Cardiel (Research unit. Primary Health Care Management Madrid. Spain), Mercedes Aza-Pascual-Salcedo (Primary Care Department, Aragonese Health Service.), Amaya Azcoaga Lorenzo (Pintores Primary Health Care Centre, Madrid, Spain), Ana Cristina Bandrés-Liso (Primary Care Department, Aragonese Health Service.), Mercedes Clerencia-Sierra (Unit of Social and Health Assessment, Miguel Servet University Hospital, Aragonese Health Service), Nuria García-Agua (Department of Pharmacology, Faculty of Medicine, Malaga University), Luis A. Gimeno Feliu (San Pablo Primary Health Care Centre, Aragon Health Service, Zaragoza, Spain), Antonio Gimeno-Miguel (Aragonese Institute of Health Sciences (IACS), IIS Aragón, Miguel Servet University Hospital, Spain), Ana I González González (Technical Support Unit, Primary Care Management, Madrid Health Service), Virginia Hernández Santiago (Ninewells Hospital & Medical School, Dundee, UK), Francisca Leiva Fernández (Multiprofessional Teaching Unit for Family and Community Care Primary Care District Málaga-Guadarhorce. Málaga), Ana M^a López-León (Alhaurín el Grande Health Centre, Malaga/Guadalhorce Sanitary District), Juan A López Rodríguez (Research unit. Primary Health Care Management Madrid. Spain), Cristina M Lozano Hernández (Research unit. Primary Health Care Management Madrid. Spain), María Isabel Márquez-Chamizo (Carranque Health Centre, Malaga/Guadalhorce Sanitary District.), Alessandra Marengoni (Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy), Javier Marta-Moreno (Department of Neurology, University Hospital Miguel Servet, Aragonese Health Service.), Jesús Martín Fernández (Villamanta Primary Health Care Centre, Madrid, Spain), Angel Mataix SanJuan (Subdirección General de Farmacia y Productos Sanitarios), Carmina Mateos-Sancho (Ciudad Jardín Health Centre, Malaga/Guadalhorce Sanitary District), Christiane Muth (Institute of General Practice, Johann Wolfgang Goethe University, Frankfurt, Germany), Victoria Pico Soler (Torrero-LaPaz Health Centre, Zaragoza, Spain), Beatriz Poblador Plou (Aragonese Institute of Health Sciences (IACS), IIS Aragón, Miguel Servet University Hospital, Spain), Elena Polentinos Castro (Research unit. Primary Health Care Management Madrid. Spain), Antonio Poncel-Falcón (Primary Care Department, Aragonese Health Service.), Ricardo Rodríguez Barrientos (Research unit. Primary Health Care Management Madrid. Spain), José María Ruiz-San-Basilio (Coín Health Centre, Malaga/Guadalhorce Sanitary District), Mercedes Rumayor Zarzuelo (6 Centro de Salud Pública de Coslada, Área II Subdirección de Promoción de la Salud y Prevención), Luis Sánchez Perruca (Dirección Sistemas de Información, Gerencia Asistencial de Atención Primaria, Servicio Madrileño de Salud), Teresa Sanz Cuesta (Research unit. Primary Health Care Management Madrid. Spain), M^a Eugenia Tello Bernabé (El naranjo Primary Health Care Centre, Madrid, Spain.), José María Valderas Martínez (University of Exeter Medical School, Exeter, UK. 22Department), Rubén Vázquez-Alarcón (Vera Health Centre, AGS Norte de Almería).

Clinical investigators in primary healthcare centres (PHC) MULTIPAP group

Andalucía: PCHC Alhaurín el Grande Javier Martín Izquierdo, Macarena Toro Sainz. PCHC Carranque Andalucía): M^a José Fernández Jiménez, Esperanza Mora García, José Manuel Navarro Jiménez. PCHC Ciudad Jardín Andalucía):: Deborah Gil Gómez, Leovigildo Ginel Mendoza, Luz Pilar de la Mota Ybancos, Jaime Sasporte Genafo.PCHC Coín Andalucía): M^a José Alcaide Rodríguez, Elena Barceló Garach, Beatriz Caffarena de Arteaga, M^a Dolores Gallego Parrilla, Catalina Sánchez Morales. PCHC Delicia Andalucía): M^a del Mar Loubet Chasco, Irene Martínez Ríos, Elena Mateo Delgado. PCHC La Roca Andalucía): Esther Martín Aurioles. PCHC Limonar Andalucía): Sylvia Hazañas Ruiz. PCHC Palmilla Andalucía): Nieves Muñoz Escalante. PCHC Puerta Blanca Andalucía): Enrique Leonés Salido, M^a Antonia Máximo Torres, M^a Luisa Moya Rodríguez, Encarnación Peláez Gálvez, José Manuel Ramírez Torres, Cristóbal Trillo Fernández. PCHC Tiro Pichón Andalucı´a): M^a Dolores García Martínez Cañavate, M^a del Mar Gil Mellado, M^a Victoria Muñoz Pradilla. PCHC Vélez Sur Andalucía): M^a José Clavijo Peña, José Leiva Fernández, Virginia Castillo Romero. PCHC Victoria Andalucía): Rafael Ángel Maqueda, Gloria Aycart Valdés, Miguel Domínguez Santaella, Ana M^a Fernández Vargas, Irene García, Antonia González Rodríguez, M^a Carmen Molina Mendaño, Juana Morales Naranjo, Catalina Moreno Torres, Francisco Serrano Guerra.

Aragón: PCHC Alcorisa (Alcorisa): Carmen Sánchez Celaya del Pozo. PCHC Delicias Norte (Zaragoza): José Ignacio Torrente Garrido, Concepción García Aranda, Marina Pinilla Lafuente, M^a Teresa Delgado Marroquín. PCHC Picarral (Zaragoza): M^a José Gracia Molina, Javier Cuartero Bernal, M^a Victoria Asín Martín, Susana García Domínguez. PCHC Fuentes de Ebro (Zaragoza): Carlos Bolea Gorbea. PCHC Valdefierro (Zaragoza): Antonio Luis Oto Negre. PCHC Actur Norte (Zaragoza): Eugenio Galve Royo, M^a Begoña Abadía Taira. PCHC Alcañiz (Alcañiz): José Fernando Tomás Gutiérrez. PCHC Sagasta— Ruiseñores (Zaragoza): José Porta Quintana, Valentina Martín Miguel, Esther Mateo de las Heras, Carmen Esteban Algora. PCHC Ejea (Ejea de los Caballeros): M^a Teresa Martín Nasarre de Letosa, Elena Gascón del Prim, Noelia Sorinas Delgado, M^a Rosario Sanjuan Cortés. PCHC Canal Imperial—Venecia (Zaragoza): Teodoro Corrales Sánchez. PCHC Canal Imperial—San José Sur (Zaragoza): Eustaquio Dendarieta Lucas. PCHC Jaca (Jaca): M^a del Pilar Mínguez Sorio. Virginia López Cortés. PCHC Santo Grial (Huesca): Adolfo Cajal Marzal.

Madrid. PCHC Mendiguchía Carriche (Leganés): Eduardo Díaz García, Juan Carlos García Álvarez, Francisca García De Blas González, Cristina Guisado Pérez, Alberto López García Franco, M^a Elisa Viñuela Benitez. PCHC El Greco (Getafe): Ana Ballarín González, M^a Isabel Ferrer Zapata, Esther Gómez Suarez, Fernanda Morales Ortiz, Lourdes Carolina Peláez Laguno, José Luis Quintana Gómez, Enrique Revilla Pascual. PCHC Cuzco (Fuenlabrada): M Ángeles Miguel Abanto. PCHC El Soto (Móstoles): Blanca Gutierrez Teira. PCHC Genera Ricardos (Madrid): Francisco Ramón Abellán López, Carlos Casado Álvaro, Paulino Cubero González, Santiago Manuel Machín Hamalainen, Raquel Mateo Fernández, M^a Eloisa Rogero Blanco, Cesar Sánchez Arce. PCHC Ibiza (Madrid): Jorge Olmedo Galindo. PCHC Las Américas (Parla): Claudia López Marcos, Soledad Lorenzo Borda, Juan Carlos Moreno Fernández, Belén Muñoz Gómez, Enrique Rodríguez De Mingo. PCHC M^a Ángeles López (Leganés): Juan Pedro Calvo Pascual, Margarita Gómez Barroso, Beatriz López Serrano, M^a Paloma Morso Peláez, Julio Sánchez Salvador, Jeannet Dolores Sánchez Yépez, Ana Sosa Alonso. PCHC M^a Jesús Hereza (Leganés): M^a del Mar A^´lvarez Villalba. PCHC Pavones (Madrid): Purificación Magán Tapia. PCHC Pedro Laín Entralgo (Alcorcón): M^a Angelica Fajardo Alcántara, M^a Canto De Hoyos Alonso, M^a Aránzazu Murciano Antón. PCHC Pintores (Parla): Manuel Antonio Alonso Pérez, Ricardo De Felipe Medina, Amaya Nuria López Laguna, Eva Martínez Cid De Rivera, Iliana Serrano Flores, M^a Jesús Sousa Rodríguez. PCHC Ramón y Cajal (Alcorcón): M^a Soledad Núñez Isabel, Jesús M^a Redondo Sánchez, Pedro Sánchez Llanos, Lourdes Visedo Campillo.

Disclosure statement

The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This study was funded by Instituto de Salud Carlos III (isciii) [file number PI18/01812, PI18/01303 y PI18/01515, RD16/0001/0004, RD16/0001/0005, RD16/0001/0006] and co-funded by the European Regional Development Fund ‘A way to shape Europe; Research, Development and Innovation Natiotal Plan 2013-2016’. ERB has received a grant from the Fundación para la Investigación e Innovación Biosanitaria de Atención Primaria (FIIBAP) for translation in 2019 call and received funding from the Sociedad Española de Medicina Familiar y comunitaria-semFYC- as it won a grant for the completion of doctoral theses Isabel Fernandez 2018.