Eur J Clin Pharmacol DOI 10.1007/s00228-015-1829-8
PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Preventability of adverse effects of analgesics: analysis of spontaneous reports Irina Cazacu & Ghada Miremont-Salamé & Cristina Mogosan & Annie Fourrier-Réglat & Felicia Loghin & Françoise Haramburu
Received: 16 September 2014 / Accepted: 23 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Objectives The aims of this study were to determine the patterns of analgesic adverse drug reactions (ADRs) and to assess their preventability and contributing factors. Methods This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported to the Bordeaux pharmacovigilance center from January 2011 to June 2012. Results The 141 cases selected for the analysis included 16 cases of medication errors (11.3 %) and 15 addiction cases (10.6 %). In total, 214 ADRs were registered, for which 173 analgesic medicines were suspected. The most frequent ADRs reported were nervous system dis-
Electronic supplementary material The online version of this article (doi:10.1007/s00228-015-1829-8) contains supplementary material, which is available to authorized users. I. Cazacu (*) : G. Miremont-Salamé : C. Mogosan : A. Fourrier-Réglat : F. Loghin : F. Haramburu Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, University of Medicine and Pharmacy BIuliu Hatieganu^, Cluj-Napoca 400012, Romania e-mail: [email protected] G. Miremont-Salamé : A. Fourrier-Réglat : F. Haramburu Regional Pharmacovigilance Centre, CHU de Bordeaux, F-33000 Bordeaux, Romania G. Miremont-Salamé : A. Fourrier-Réglat INSERM U657, F-33000 Bordeaux, France A. Fourrier-Réglat University of Bordeaux, F-33000 Bordeaux, France F. Loghin Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy BIuliu Hatieganu^, Cluj-Napoca 400012, Romania
orders (26.6 %), psychiatric disorders (15.0 %), and skin and subcutaneous tissue disorders (12.1 %). Tramadol alone or in combination (17.3 %), followed by morphine (15 %), fentanyl (9.8 %), and paracetamol (8.7 %) were the most frequently involved analgesics. More than half of the cases (54.6 %) were serious and led to hospitalization or prolonged hospitalization. Preventability was determined for 134 cases (95 %): 51.5 % were considered as preventable, 26.1 % not preventable, and 22.4 % not assessable. The main contributing factors for the preventable cases included negligence of recommendations for analgesic use and failure to consider patients’ risk factors when prescribing. Conclusions A significant number of analgesic ADRs could be prevented, and being aware of their contributing factors promotes efficient analgesia with minimum risks to the patients. Keywords Analgesics . Adverse drug reactions . Patient harm
Introduction Analgesics are among the most frequently used medicines all over the world for the treatment of various types of pain, including vulnerable populations such as children, pregnant women, and the elderly [1–4]. Pain is a highly prevalent symptom, with a great impact on patients’ life [5, 6]. The availability nowadays of various types of analgesics and the potential for some of them to be misused drew more attention on the management of pain [7, 8]. Adverse drug reactions (ADRs) are a well-known cause of mortality and morbidity among patients, being between the fourth and sixth leading cause of death [9]. They represent a
Eur J Clin Pharmacol
significant cause of hospital admissions in most countries [10–12]. France was found between the countries with a high analgesic consumption in comparison with other European countries [13]. Furthermore, analgesics are between the drugs most frequently responsible for ADRs in France [11, 14]. Analyzing the ADRs of analgesics and understanding their causes could be thus useful for implementing risk-minimizing strategies. Spontaneous reporting system is an invaluable way to collect safety information on medicines after their approval, with details on the ADR cases most often not available in the results of clinical trials or pharmacoepidemiological studies. The aims of the present study were to characterize patterns of spontaneous ADR reports for analgesics and to assess their preventability and contributing factors.
Table 1
Characteristics of analgesics involved in ADR cases (n=134)
ATC
Analgesic group
Main representatives
Methods A descriptive, retrospective study was conducted on analgesic ADR cases reported to the Bordeaux pharmacovigilance center by both health professionals and patients during a period of 18 months, from January 2011 to June 2012. ADR and seriousness definitions were those of the European Union Pharmacovigilance legislation available since 2012 [15]. Data were extracted from the local database by using the Anatomical, Therapeutic and Chemical (ATC) classification of drugs. Therefore, specific analgesics such as nonopioid (analgesics-antipyretics, non-steroidal anti-inflammatory drugs [NSAIDs], treatment for acute migraine [triptans]) and opioid drugs, as well as other drug classes (anticonvulsants, antidepressants), if used for pain, were retained in the
All casesb No. of cases (%)
N02A
Opioids
N02B
Analgesics and antipyretics
N03A
Anticonvulsants
M01A
NSAIDs
N02C
Treatment for acute migraine
N06A
Antidepressants
Preventable cases No. of serious cases (%)
No. of preventable cases (%)
No. of serious and preventable cases (%)
All
80 (59.7)
49 (36.6)
52 (38.8)
39 (29.1)
Tramadola Morphine Fentanyl Oxycodone Othersc All Paracetamola Othersd All Pregabalin Otherse All Ibuprofen Othersf All Zolmitriptan Sumatriptan All
27 (20.1) 24 (17.9) 14 (10.4) 12 (9) 13 (9.7) 31 (23.1) 15 (11.2) 17 (12.7) 18 (13.4) 15 (11.2) 3 (–) 15 (11.2) 10 (7.5) 6 (4.5) 5 (3.7) 4 (–) 2 (–) 3 (–)
11 (8.2) 15 (11.2) 13 (9.7) 7 (5.2) 9 (6.7) 12 (9) 6 (4.5) 7 (5.2) 5 (3.7) 5 (3.7) 0 13 (9.7) 8 (6) 6 (4.5) 3 (–) 3 (–) 1 (–) 0
16 (11.9) 17 (12.7) 11 (8.2) 11 (8.2) 6 (4.5) 12 (9) 7 (5.2) 6 (4.5) 3 (–) 3 (–) 0 7 (5.2) 3 (–) 4 (–) 3 (–) 2 (–) 2 (–) 1 (–)
9 (6.7) 13 (9.7) 11 (8.2) 7 (5.2) 4 (–) 7 (5.2) 4 (–) 4 (–) 1 (–) 1 (–) 0 6 (4.5) 2 (–) 4 (–) 2 (–) 2 (–) 1 (–) 0
Amitriptyline Duloxetine
2 (–) 1 (–)
0 0
1 (–) 0
0 0
a
Drugs discussed in the paper
b
Total number of cases >134 as more than one analgesic could have been involved in an ADR case report Percentages not calculated when n
PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Preventability of adverse effects of analgesics: analysis of spontaneous reports Irina Cazacu & Ghada Miremont-Salamé & Cristina Mogosan & Annie Fourrier-Réglat & Felicia Loghin & Françoise Haramburu
Received: 16 September 2014 / Accepted: 23 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Objectives The aims of this study were to determine the patterns of analgesic adverse drug reactions (ADRs) and to assess their preventability and contributing factors. Methods This is a retrospective, descriptive study conducted on ADRs of analgesics and other drugs indicated as analgesics, spontaneously reported to the Bordeaux pharmacovigilance center from January 2011 to June 2012. Results The 141 cases selected for the analysis included 16 cases of medication errors (11.3 %) and 15 addiction cases (10.6 %). In total, 214 ADRs were registered, for which 173 analgesic medicines were suspected. The most frequent ADRs reported were nervous system dis-
Electronic supplementary material The online version of this article (doi:10.1007/s00228-015-1829-8) contains supplementary material, which is available to authorized users. I. Cazacu (*) : G. Miremont-Salamé : C. Mogosan : A. Fourrier-Réglat : F. Loghin : F. Haramburu Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, University of Medicine and Pharmacy BIuliu Hatieganu^, Cluj-Napoca 400012, Romania e-mail: [email protected] G. Miremont-Salamé : A. Fourrier-Réglat : F. Haramburu Regional Pharmacovigilance Centre, CHU de Bordeaux, F-33000 Bordeaux, Romania G. Miremont-Salamé : A. Fourrier-Réglat INSERM U657, F-33000 Bordeaux, France A. Fourrier-Réglat University of Bordeaux, F-33000 Bordeaux, France F. Loghin Department of Toxicology, Faculty of Pharmacy, University of Medicine and Pharmacy BIuliu Hatieganu^, Cluj-Napoca 400012, Romania
orders (26.6 %), psychiatric disorders (15.0 %), and skin and subcutaneous tissue disorders (12.1 %). Tramadol alone or in combination (17.3 %), followed by morphine (15 %), fentanyl (9.8 %), and paracetamol (8.7 %) were the most frequently involved analgesics. More than half of the cases (54.6 %) were serious and led to hospitalization or prolonged hospitalization. Preventability was determined for 134 cases (95 %): 51.5 % were considered as preventable, 26.1 % not preventable, and 22.4 % not assessable. The main contributing factors for the preventable cases included negligence of recommendations for analgesic use and failure to consider patients’ risk factors when prescribing. Conclusions A significant number of analgesic ADRs could be prevented, and being aware of their contributing factors promotes efficient analgesia with minimum risks to the patients. Keywords Analgesics . Adverse drug reactions . Patient harm
Introduction Analgesics are among the most frequently used medicines all over the world for the treatment of various types of pain, including vulnerable populations such as children, pregnant women, and the elderly [1–4]. Pain is a highly prevalent symptom, with a great impact on patients’ life [5, 6]. The availability nowadays of various types of analgesics and the potential for some of them to be misused drew more attention on the management of pain [7, 8]. Adverse drug reactions (ADRs) are a well-known cause of mortality and morbidity among patients, being between the fourth and sixth leading cause of death [9]. They represent a
Eur J Clin Pharmacol
significant cause of hospital admissions in most countries [10–12]. France was found between the countries with a high analgesic consumption in comparison with other European countries [13]. Furthermore, analgesics are between the drugs most frequently responsible for ADRs in France [11, 14]. Analyzing the ADRs of analgesics and understanding their causes could be thus useful for implementing risk-minimizing strategies. Spontaneous reporting system is an invaluable way to collect safety information on medicines after their approval, with details on the ADR cases most often not available in the results of clinical trials or pharmacoepidemiological studies. The aims of the present study were to characterize patterns of spontaneous ADR reports for analgesics and to assess their preventability and contributing factors.
Table 1
Characteristics of analgesics involved in ADR cases (n=134)
ATC
Analgesic group
Main representatives
Methods A descriptive, retrospective study was conducted on analgesic ADR cases reported to the Bordeaux pharmacovigilance center by both health professionals and patients during a period of 18 months, from January 2011 to June 2012. ADR and seriousness definitions were those of the European Union Pharmacovigilance legislation available since 2012 [15]. Data were extracted from the local database by using the Anatomical, Therapeutic and Chemical (ATC) classification of drugs. Therefore, specific analgesics such as nonopioid (analgesics-antipyretics, non-steroidal anti-inflammatory drugs [NSAIDs], treatment for acute migraine [triptans]) and opioid drugs, as well as other drug classes (anticonvulsants, antidepressants), if used for pain, were retained in the
All casesb No. of cases (%)
N02A
Opioids
N02B
Analgesics and antipyretics
N03A
Anticonvulsants
M01A
NSAIDs
N02C
Treatment for acute migraine
N06A
Antidepressants
Preventable cases No. of serious cases (%)
No. of preventable cases (%)
No. of serious and preventable cases (%)
All
80 (59.7)
49 (36.6)
52 (38.8)
39 (29.1)
Tramadola Morphine Fentanyl Oxycodone Othersc All Paracetamola Othersd All Pregabalin Otherse All Ibuprofen Othersf All Zolmitriptan Sumatriptan All
27 (20.1) 24 (17.9) 14 (10.4) 12 (9) 13 (9.7) 31 (23.1) 15 (11.2) 17 (12.7) 18 (13.4) 15 (11.2) 3 (–) 15 (11.2) 10 (7.5) 6 (4.5) 5 (3.7) 4 (–) 2 (–) 3 (–)
11 (8.2) 15 (11.2) 13 (9.7) 7 (5.2) 9 (6.7) 12 (9) 6 (4.5) 7 (5.2) 5 (3.7) 5 (3.7) 0 13 (9.7) 8 (6) 6 (4.5) 3 (–) 3 (–) 1 (–) 0
16 (11.9) 17 (12.7) 11 (8.2) 11 (8.2) 6 (4.5) 12 (9) 7 (5.2) 6 (4.5) 3 (–) 3 (–) 0 7 (5.2) 3 (–) 4 (–) 3 (–) 2 (–) 2 (–) 1 (–)
9 (6.7) 13 (9.7) 11 (8.2) 7 (5.2) 4 (–) 7 (5.2) 4 (–) 4 (–) 1 (–) 1 (–) 0 6 (4.5) 2 (–) 4 (–) 2 (–) 2 (–) 1 (–) 0
Amitriptyline Duloxetine
2 (–) 1 (–)
0 0
1 (–) 0
0 0
a
Drugs discussed in the paper
b
Total number of cases >134 as more than one analgesic could have been involved in an ADR case report Percentages not calculated when n
