Pediatric Drug Safety Surveillance: A 10-Year Analysis of Adverse Drug Reaction Reporting Data in Calabria, Southern Italy.

INTRODUCTION: The paucity of pediatric clinical trials has led to many medicines frequently prescribed to children without a license for use in pediatrics, resulting in an increased risk of adverse drug reactions. Pharmacovigilance databases remain, among others, a valuable tool for evaluating pediatric drug safety in the real-life setting. OBJECTIVE: We aimed to characterize pediatric adverse drug reactions reported in the Italian Pharmacovigilance database coming from the Calabria region (Southern Italy) over 10 years. METHODS: All Individual Case Safety Reports (ICSRs) concerning individuals aged under 18 years were extracted from 2010 to 2019. Duplicate and vaccine ICSRs were excluded. The remaining ICSRs were analyzed with respect to patients' demographic data, suspected drugs, and category of adverse drug reactions across different age groups. RESULTS: Among 6529 selected ICSRs, 395 pediatric ICSRs corresponding to 556 adverse drug reactions were analyzed. From 2010 to 2015, an increasing number of ICSRs were observed, but the reporting rate decreased after 2015. The highest proportion of ICSRs concerned children and adolescents. Around 52% of ICSRs involved boys: a trend observed in all age groups excluding newborns. Sixty ICSRs were serious and among them, 75% required hospitalization mainly in children and adolescents. Most of the ICSRs were issued by physicians (64.1%), followed by other healthcare professionals (22.5%) and pharmacists (9.9%). Anti-infective agents for systemic use and skin disorders were, respectively, the most frequently reported drug group and adverse drug reaction category. CONCLUSIONS: This study provides an overview of adverse drug reactions reported in the pediatric population of the Calabria region and emphasizes the need for strengthening the surveillance in specific age subgroups and on given drugs in relation to their pattern of use.

Pattern of treatment of behavioural and psychological symptoms of dementia and pain: evidence on pharmacoutilization from a large real-world sample and from a centre for cognitive disturbances and dementia.

PURPOSE: Data concerning the number of diagnoses and of the drugs prescribed to patients affected by dementia are still scarce. Here we test whether or not (1) prescription of symptomatic drugs against Alzheimer's disease (AD) may approximate the number of patients affected by dementia in Italy and (2) adherence to this treatment affects the pattern of prescription of drugs (i.e. antipsychotics and antidepressants) for behavioural and psychological symptoms of dementia (BPSD) and the previously reported limited prescription of analgesics. METHODS: This retrospective observational study concerns 84,235 subjects older than 60 years and registered in the provincial prescription database of the health district of Cosenza accounting for a population of 298,000 inhabitants. The prescribing pattern of antipsychotics, antidepressants, and analgesics has been investigated in patients receiving concurrent prescriptions of acetylcholinesterase inhibitors (AChEI) and/or memantine. Data from a single centre for cognitive disturbances and dementia (CDCD) in the same health district were used to explore at which stage dementia was diagnosed. The study was approved by Calabria Region Ethical Committee no. 31/2017 and registered on October 31, 2017. RESULTS: The data show that 859 patients are treated with AChEI and/or memantine; 420 patients (48.89%) receive at least 80% of the recommended medications. CDCD data indicate a delay in dementia diagnosis, which often was made when the patients were moderately to severely demented (Mini Mental State Examination, MMSE ≤ 20). Adherence did not influence prescription of most of the drugs explored, but use of non-steroidal anti-inflammatory drugs was higher in non-adherent patients. Antipsychotics and antidepressants are frequently used (20.61-20.71% and 42.37-51.43%, respectively), and this, at least in part, might stem from the observed under-treatment of chronic pain (opioids are prescribed in the 4.76% and 12.46% of adherent and non-adherent patients and gabapentin and pregabalin are used in the 4.29% and 4.07% of adherent and non-adherent patients respectively), resulting in more frequent BPSD. 16.43% of patients receive antipsychotics for longer than 6-12 weeks. CONCLUSION: This 2-year period study, including a wide cohort of community demented patients, shows that dementia is diagnosed late and that prevalence of BPSD prescriptions is high and not impacted by adherence to anti-dementia drugs. The rate of prescription of potentially harmful antipsychotics and antidepressants appears to be high though whether the concomitantly observed limited prescription of analgesics might be a contributing factor needs to be further investigated. Our data support the development of strategies to improve the management of BPSD.

Safety and efficacy of generic drugs with respect to brand formulation.

Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.