Inadvertent oral administration of methylergometrine maleate to children in the first months of life: from surveillance to prevention.

PURPOSE: Methylergometrine maleate is an ergot alkaloid frequently used in obstetrics for prevention and treatment of post partum haemorrhage. Accidental administration of this medicine to newborns can cause severe effects and should be carefully prevented. The present paper is aimed at describing the main characteristics of cases accidentally exposed to this medicine in Italy before and after Novartis, the manufacturer of Methergin®, a widely used methylergometrine maleate-containing gynecological medication, decided to withdraw the drop preparation from the European market. METHODS: The study design is a case-series study. The database of the National Poison Control Centre of Milan was searched retrospectively (from 1 January 2005 to 31 December 2011) and prospectively (from 1 January 2012 to 31 December 2013) in order to provide a descriptive analysis of the main characteristics of cases unintentionally exposed to methylergometrine maleate and to document the impact of Novartis' decision. RESULTS: In the first period under study (2005-2011), a total of 642 cases of exposure to methylergometrine maleate were identified. Most of them were children aged <1 year (No. 483, 75%). Patients aged 1-2 and 3-5 years accounted for 13% (No. 85) and 9% (No. 56) of cases, respectively. Among children aged <1 year, about 76% (No. 368) were exposed during the first month of life, including 44% (No. 211) of cases exposed in the first week of life. The main cause of exposure was medication error (No. 432, 89%), mainly due to oral administration of methyltergometrine maleate in place of a paediatric preparation (No. 469, 97%). About 14% of these cases suffered clinical effects as a consequence of the exposure. Severity of poisoning was minor in 45 cases, moderate in 12, and severe in one case. The main cause of exposure among children aged 1-2 and 3-5 years was uncontrolled access to the medicine, accounting for 78% (No. 66) and 77% (No. 43) of cases, respectively. Some 9% (No. 8) of cases aged 1-2 years and 7% (No. 4) of those aged 3-5 years developed signs/symptoms possibly related to the exposure. For all of them, severity of clinical effects was low, but one case suffered moderate effects. Exposure to the medicine in drops was reported for 87% (No. 74) and 84% (No. 47) of cases aged 1-2 and 3-5 years, respectively. In 2012-2013 a total of 25 cases were observed. Among them, two patients were aged <1 year (8%). Both cases occurred in 2012 and were inadvertently administered the medicine in drops still available (present) in the home. Fourteen (56%) and 8 (32%) cases were aged 1-2 and 3-5 years, respectively. All of them were exposed to the tablet formulation following uncontrolled access to the medicine. CONCLUSIONS: The observations here reported indicate that having different formulations for methylergometrine maleate-containing products intended for the mother and paediatric medicines can successfully prevent medication error due to medicine exchange in the first months of life.

Safety profile of antiviral medications: a pharmacovigilance study using the Italian spontaneous-reporting database.

PURPOSE: The results of an analysis of suspected antiviral-associated adverse drug reactions (ADRs) in Italy over a 22-year period are presented. METHODS: A case/non-case analysis was conducted using ADR reports compiled in the nationwide spontaneous-reporting database through September 2010. All reported events included in the analysis were evaluated and coded by drug safety experts; causality assessments were performed according to the algorithm of Naranjo et al. The association between an adverse reaction and antiviral use was assessed by estimating the reporting odds ratio (ROR), with 95% confidence interval (CI), as a measure of disproportionality. RESULTS: Overall, 863 reports of suspected ADRs involving antivirals and 42,430 reports of adverse reactions to other drugs were identified; of those events, 3.3% and 64.3% were determined to be definite or probable ADRs, respectively, and an additional 32.4% were deemed possibly drug related. Several ADRs were disproportionately associated with antivirals relative to other drugs: renal colic (ROR, 25.5; 95% CI, 13.3-49.0), lactic acidosis (ROR, 18.6; 95% CI, 9.2-37.7), depression (ROR, 18.0; 95% CI, 11.6-27.9), anemia (ROR, 15.9; 95% CI, 12.3-20.4), hallucination (ROR, 4.3; 95% CI, 2.7-7.1), neutropenia (ROR, 4.1; 95% CI, 2.9-5.8), acute renal failure (ROR, 3.9; 95% CI, 2.3-6.4), fever (ROR, 3.8; 95% CI, 2.8-5.1), hyperpyrexia (ROR, 2.9; 95% CI, 1.7-4.9), and asthenia (ROR, 1.8; 95% CI, 1.2-2.8). CONCLUSION: Analysis of data from a large Italian database showed that, among antiviral agents, the ribavirin-interferon combination, acyclovir, valacyclovir, indinavir, and zidovudine accounted for the most serious hematologic, neuropsychiatric, and renal ADRs.

Adverse drug reaction reporting by nurses: analysis of Italian pharmacovigilance database.

PURPOSE: The aim of this study was to describe the pattern of adverse drug reaction (ADR) reports sent by Italian nurses after the enactment of the law involving them in the pharmacovigilance system. We also compared the quantity and quality of reports by nurses with those of reports by hospital physicians sent in the same period. METHODS: We analysed the reports sent to the Italian pharmacovigilance database by nurses from January 2004 to December 2010. Only reports with ADRs causality assessment defined as definite, probable or possible were included in the analysis. The nurses' reports were compared with those sent by hospital physicians in the same period. We excluded from this analysis reports associated with vaccines. RESULTS: A total number of 1403 reports by nurses have been evaluated. The percentage of nurses' reports of ADRs, which were serious, were 22.9% lower than the 44.9% of reports by physicians, whereas the proportion of probable ADR reports were higher among nurses than hospital physicians (76% vs 67%). Nurses put more emphasis than physicians on application site disorders (log OR = 0.91, 95%CI = 0.55-1.27), skin reactions (log OR = 0.81, 95%CI = 0.70-0.92) and nervous system reactions (log OR = 0.28, 95%CI = 0.11-0.44), whereas physicians more frequently report blood, platelet and liver disorders. Six drugs are present in both the top 10 drugs reported by nurses and hospital doctors. CONCLUSION: This study gives evidence for the potential capacity of nurses to improve the detection of ADRs.

Oral ingestion of a topical benzydamine hydrochloride-containing gynaecological preparation in association with television advertising in Italy: analysis of cases managed by a National Poison Control Centre.

Objective To evaluate the impact of a television advertising campaign on the risk of oral ingestion of a topical non-prescription gynaecological preparation containing benzydamine hydrochloride. Design An interrupted time series design with data routinely collected. Setting A National Poison Control Centre. Participants 215 cases of hazardous exposure to the preparation under study occurred in Italy from January 2005 to December 2010. Primary and secondary outcome measures Mean daily rate of cases of exposure by gender in three different periods, that is, pre-advertisement period, before the advertisement was broadcast (from 1 January 2005 to 19 December 2009), advertisement period, when the advertisement was repeatedly launched (from 20 December 2009 to 27 February 2010), post-advertisement period (from 28 February 2010 to 6 March 2010); observed/expected ratios of cases, with expected cases based on data from the pre-advertisement period, adjusted for estimated variations in the number of users. Comparison of the distribution of the main characteristics of cases in the three different periods by means of Pearson's χ(2) test or Fisher's exact test. Results The adjusted observed/expected ratio of cases in women was 7.48 (95% CI 5.76 to 9.56) in the advertisement period and 2.97 (95% CI 2.24 to 3.85) in the post-advertisement period. Regarding the characteristics of cases, there was an increased proportion of cases of exposure due to confusion about the correct administration route in the advertisement and post-advertisement periods (81% and 55%, respectively, compared to 16% for the pre-advertisement period.) and of individuals with clinical effects (55%, 52% and 27%, respectively). Conclusions In Italy, an advertisement for a non-prescription medicine seems to have confused consumers regarding the administration route. This effect was observed even after the advertisement had stopped being broadcast. These results highlight the need for the monitoring of medication errors and adverse effects before, during and after advertising.

Drug-induced taste and smell alterations: a case/non-case evaluation of an italian database of spontaneous adverse drug reaction reporting.

BACKGROUND: The frequency and clinical features of drug-related taste and/or smell impairments are currently unclear. OBJECTIVE: The aim of this study was to identify major drug classes associated with taste and smell alterations reported to the Italian spontaneous adverse drug reaction (ADR) reporting database. METHODS: The association between drug and altered taste or smell was investigated by case/non-case methodology. The reporting odds ratio (ROR) was used as a measure of disproportionality. Cases were defined as patients with at least one ADR related to taste or smell impairments. The non-cases included all patients without any ADRs related to taste or smell alterations. RESULTS: According to the selection criteria, 52 166 reports were included in the analysis. Overall, 182 cases of drug-related taste and/or smell dysfunctions were identified. Statistically significant unadjusted RORs were reported for macrolides (n = 31; 7.1; 95% CI 4.8, 10.5), terbinafine (the only drug reported within the group of antimycotics belonging to the Anatomical Therapeutic Chemical class D01AE) [n = 17; 76.4; 95% CI 44.0, 132.6], fluoroquinolones (n = 15; 1.7; 95% CI 1.0, 2.8) and protein kinase inhibitors (n = 10; 4.0; 95% CI 2.1, 7.7). When RORs were adjusted for sex and age category, the disproportion remained statistically significant for all of the previously mentioned drug classes. CONCLUSIONS: Taste and/or smell abnormalities are common, sometimes unexpected and often persistent complaints of patients during pharmacological treatments. Physicians should be aware of the impact of these ADRs on patients' quality of life.

Italian post-marketing surveillance for adverse event reports after MF59-adjuvanted H1N1v vaccination.

According to European recommendations, the Italian Medicines Agency (AIFA) required close monitoring of the safety of the MF59-adjuvanted H1N1v vaccine, which was the only vaccine available in Italy for prophylaxis of the A/H1N1 (2009) pandemic influenza. From October 2009 to June 2010, the Italian Pharmacovigilance Adverse Event (AE) Spontaneous Reporting System [Rete Nazionale Farmacovigilanza] (RNF) received 1330 reports of AEs temporally related with the pandemic influenza vaccination out of a total of 924,057 doses administered. Among these, 1,162 (87.37%) AE reports were classified 'non serious', 91 (6.84%) 'serious', 3 (0.23%) had a fatal outcome and 74 (5.56%) did not include the degree of seriousness. Among the serious AE reports, some unexpected AEs emerged. Even though some typical vaccine safety issues which emerged should be further explored, such as vaccination in pregnancy, the analysis of all AE reports sent to RNF shows that the vaccine has a well-tolerated safety profile which resembles that of the already available seasonal influenza vaccines. This contrasts with the widespread public concern about its safety, which has been one of the major causes of the low vaccination rate observed in Italy, as well as in other countries.