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Safety aspects of iodinated contrast media related to their physicochemical properties: a pharmacoepidemiology study in two Tuscany hospitals

  • Pharmacoepidemiology and Prescription
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Abstract

Background

More than 380,000 angiographic procedures are performed every year in Italian hospitals, with an increase rate of 8% per year. Although contrast media (CM) are considered relatively safe, adverse drug reactions (ADRs) remain an important issue.

Objectives

The objective of this study was to quantify the incidence of immediate and delayed nonrenal ADRs to iodinated CM in an Italian cohort and to evaluate whether their different physicochemical properties are able to affect the incidence of immediate or delayed ADRs.

Methods

A prospective intensive monitoring study was conducted on a cohort of patients undergoing radiodiagnostic procedures with iodinated CM enrolled in two hospitals in Tuscany, Italy. To evaluate both immediate (within 1 h after CM administration) and delayed (>1 h to 1 week after CM administration) ADRs to CM, two questionnaires were administered. Adverse events (AEs) were analyzed to check the causality assessment between CM and ADR. If more than one symptom occurred in the same patient, they were treated as a single event.

Results

One thousand five hundred and fourteen subjects who were exposed to iodinated CM completed the questionnaires. Mean age [standard deviation (SD)] was 65.4 (13.3) years, and 57.9% were male patients. A total of 178 [11.8%; 95% confidence interval (CI) 10.1–13.4] ADRs were reported. Thirty-four (2.2%; 1.5–3.1) and 144 (9.5%; 8.0–11.1) developed immediate and delayed ADRs, respectively. Both types of ADRs were experienced by six subjects (0.4%; 0.1–0.8). One hundred and seventy-six cases (98.8%; 96.0–99.8) were classified as possible and two (1.1%; 0.1–3.9) as probable ADRs. Monomeric low-osmolal (iopromide, iomeprol, iobitridol) and dimeric iso-osmolal (iodixanol) groups mainly reported delayed allergy-like ADRs of mild severity. Only one immediate reaction was severe. Multivariate analysis confirmed a higher risk of immediate reactions occurring for monomeric CM (OR 4.3; 95% CI 1.2–15.7), whereas the risk of delayed ADRs was significantly higher for the dimeric group (OR 1.8; 1.1–2.5).

Conclusions

Monomeric CM were more frequently involved in immediate ADRs, whereas dimeric CM were involved in delayed reactions. Although severe life-threatening ADRs to CM were confirmed to be rare, due to the large use of these drugs, they still retain clinical and epidemiological significance.

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Acknowledgements

This study was supported by a research grant from the nonprofit Drug Education and Investigation (DEI) Foundation (Italian Society of Pharmacology). We are very grateful to all radiologists (Prof. Natale Villari, Prof. Giovanni Capaccioli, Prof. Stefano Colagrande, Prof. Mario Mascalchi, Dr. Luigi Magi Diligenti, Dr. Gian Paolo Giordano, Dr. Paolo Simonelli, Dr. Luigi Rega, Dr. Manlio Acquafresca, Dr. Catia Dini, Dr. Gianni Pellicanò, Dr. Raffaella Giannini, Dr. Patrizio Pacini, Dr. Luca Carmignani, Dr. Davide Gadda, Dr. Andrea Pagliari, Dr. Franco Niccolai, Dr. Letizia Vannucchi, Dr. Anna Neri, Dr. Giuseppe Bellandi, Dr. Alessandro Bartolini, Dr. Leonardo Moreschi, Dr. Adriano Viviani, Dr. Enrico Ricci, Dr. Elena Zipoli, Dr. Alessandra Pagliani, Dr. Mauro Rossi, Dr. Daniele Varanini, Dr. Roberto Becherini, Dr. Antonio Giomi, Dr. Luigi Lavorini, Dr. William Vergoni), nurses (Mara Ridoni, Maria Pina Corbelli, Margherita Malavolti, Noris Bruni, Barbara Beneforti, Alberto Propati, Simonetta Aiazzi, Franco Romaniello, Sonia Chiti, Marzia Ferri, Marco Centini, Adele Nenci, Monica Guarascio, Monica Micheli), radiology technicians (Davide Tassi, Roberto Delli Ponti, Riccardo Terreni, Pierluigi Russo, Caterina Lazzerini, Luca Del Nista, Nunzio Piccolo, Donato Piccolo, Vinicio Paoletti, Alba Giaimo, Stefano Cappellini, Stefano Favelli, Piero Di Meo, Salvatore Castiglia, Alessandra Gavazzi, Rossella Nesti), and hospital pharmacists (Dr. Federico Romagnoli, Dr. Federica Mafucci, Dr. Matteo Lorenzo Lombardi, Dr. Barbara Fredducci) who took part to study planning and data collection. The authors have no conflicts of interest that are directly relevant to the content of the study.

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Authors and Affiliations

  1. Tuscan Regional Centre of Pharmacovigilance, Department of Pharmacology, University of Florence, Viale G. Pieraccini n°6, 50139, Florence, Italy

    Francesco Lapi, Grazia Banchelli, Alfredo Vannacci, Marina Di Pirro, Martina Moschini & Alessandro Mugelli

  2. Tuscan Regional Centre of Pharmacovigilance, Emergency Department, ASL4 Hospital, Prato, Italy

    Enrica Cecchi

  3. Department of Geriatric Medicine, University Campus Bio-Medico, Rome, Italy

    Claudio Pedone

  4. Tuscan Regional Centre of Pharmacovigilance, Hospital Pharmacy, AOU Careggi Hospital, Florence, Italy

    Francesco Attanasio, Elisabetta Cini & Enrico Tendi

  5. Hospital Pharmacy, ASL3 Hospital, Pistoia, Italy

    Valentina Berni & Antonino Scalia

  6. Department of Pharmacology, University of Florence, Florence, Italy

    Enrica Cecchi & Rosanna Matucci

Authors
  1. Francesco Lapi
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  2. Enrica Cecchi
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  3. Claudio Pedone
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  4. Francesco Attanasio
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  7. Marina Di Pirro
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  9. Valentina Berni
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  10. Rosanna Matucci
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  11. Elisabetta Cini
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  12. Antonino Scalia
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  13. Enrico Tendi
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  14. Alessandro Mugelli
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Corresponding author

Correspondence to Francesco Lapi.

Appendices

Appendix 1. Questionnaire to assess possible immediate adverse events to contrast media

Appendix 2. Questionnaire to assess possible delayed adverse events due to contrast media (administered by phone or face-to-face by a trained pharmacist after checking the previously collected information on the patient, exept for possible occurrence of immediate event)

Appendix 3

Table 6 Comparison of outpatients and inpatients characteristics
Full size table

Comments on patients status

A univariate analysis was performed to compare features of inpatients and outpatients: as shown in Table 6 additional characteristics to Table 1 with a significant different distribution between groups, were comorbidity, previous examination with ICM, antiasthmatic drugs, other diseases, and other drugs.

When all factors, including these additional ones, were included into a logistic model having DRs as outcome variable, analogous results were obtained for patient status (OR 1.5; 1.1–2.3, p = 0.020).

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Lapi, F., Cecchi, E., Pedone, C. et al. Safety aspects of iodinated contrast media related to their physicochemical properties: a pharmacoepidemiology study in two Tuscany hospitals. Eur J Clin Pharmacol 64, 723–737 (2008). https://doi.org/10.1007/s00228-008-0477-7

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  • DOI: https://doi.org/10.1007/s00228-008-0477-7

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