L’importanza della safety delle terapie cardiovascolari: aspetti di metodo e applicazioni

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Challenges for Drug Repurposing in the COVID-19 Pandemic Era

The coronavirus disease (COVID-19) pandemic has affected an estimated 16 million persons and caused 0.6 million deaths worldwide by September 2020. The pandemic has led to a rush to repurpose existing drugs, although the underlying evidence base is of variable quality. The improving knowledge of the virology and clinical presentation of COVID-19 is leading to a broadening pool of potential pharmacological targets. The aim of this review is to describe regulatory and pharmacological aspects of drug repurposing and to identify drugs proposed for repurposing in COVID-19 based on registered clinical trials, discussing the evidence to support their use in the treatment of this disease. The challenges of the correct interpretation of existing pre-clinical/clinical evidence as well as the generation of new evidence concerning drug repurposing in COVID-19 will also be discussed

Psoriasis and psoriasiform reactions secondary to immune checkpoint inhibitors

The advent of Immune Checkpoint Inhibitors (ICIs) as a standard of care for several cancers, including melanoma and head/neck squamous cell carcinoma has changed the therapeutic approach to these conditions, drawing at the same time the attention on some safety issues related to their use. To assess the incidence of psoriasis as a specific immune-related cutaneous adverse event attributing to ICIs using the Eudravigilance reporting system. All reports of adverse drug reactions (ADRs) concerning either exacerbation of psoriasis or de novo onset of psoriasis/psoriasiform reactions associated to the use of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) inhibitors ipilimumab and tremelimumab, and the Programmed cell Death protein 1/Programmed Death-Ligand 1 (PD-1/PD-L1) inhibitors nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and cemiplimab were identified and extracted from the Eudravigilance reporting system, during the period between the date of market licensing (for each study drug) and 30 October 2020. 8213 reports of cutaneous ADRs associated with at least one of study drug have been recorded, of which 315 (3.8%) reporting psoriasis and/or psoriasiform reactions as ADR. In 70.8% of reports patients had pre-existing disease. ICIs-related skin toxicity is a well-established phenomenon, presenting with several conditions, sustained by an immune background based on the activity of some cells (CD4+/CD8+ T-cells, neutrophils, eosinophils, and plasmocytes), inflammatory mediators, chemokines, and tumor-specific antibodies. In this setting, psoriasis represents probably the most paradigmatic model of these reactions, thus requiring adequate recognition as no guidelines on management are now available

Management of cancer-associated anemia with erythropoiesis-stimulating agents: ASCO/ASH clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology (ASCO)/American Society of Hematology (ASH) recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. METHODS: PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) and meta-analyses of RCTs in patients with cancer published from January 31, 2010, through May 14, 2018. For biosimilar ESAs, the literature search was expanded to include meta-analyses and RCTs in patients with cancer or chronic kidney disease and cohort studies in patients with cancer due to limited RCT evidence in the cancer setting. ASCO and ASH convened an Expert Panel to review the evidence and revise previous recommendations as needed. RESULTS: The primary literature review included 15 meta-analyses of RCTs and two RCTs. A growing body of evidence suggests that adding iron to treatment with an ESA may improve hematopoietic response and reduce the likelihood of RBC transfusion. The biosimilar literature review suggested that biosimilars of epoetin alfa have similar efficacy and safety to reference products, although evidence in cancer remains limited. RECOMMENDATIONS: ESAs (including biosimilars) may be offered to patients with chemotherapy-associated anemia whose cancer treatment is not curative in intent and whose hemoglobin has declined to \u3c 10 g/dL. RBC transfusion is also an option. With the exception of selected patients with myelodysplastic syndromes, ESAs should not be offered to most patients with nonchemotherapy-associated anemia. During ESA treatment, hemoglobin may be increased to the lowest concentration needed to avoid transfusions. Iron replacement may be used to improve hemoglobin response and reduce RBC transfusions for patients receiving ESA with or without iron deficiency. Additional information is available at www.asco.org/supportive-care-guidelines and www.hematology.org/guidelines

Gender Differences in Outpatient Pediatric Drug Utilization: A Cohort Study From Southern Italy

Objective: The aim of this retrospective population-based cohort study is to in-depth investigate gender-specific drug utilization pattern in pediatric outpatient population.Methods: By using a large administrative database of the Local Health Unit of Caserta (Southern Italy), a pediatric cohort from the birth to 18 years was observed over 6 years (from 1st January 2010 to 31st December 2015). Yearly prevalence of drug use per 100 inhabitants as well as the median number of prescriptions was stratifying by gender. Prevalence of acute and recurrent use of the most frequently used active substances was calculated for the year 2015.Results: A decreasing trend in prevalence of drug use (−3.2%, with a reduction of median number of drugs dispensed) was observed in children for both sexes, from 2010 to 2015. In 2015, the drug classes most commonly used among children of any age were modestly but consistently prescribed more to males than to females: systemic anti-infective drugs (M = 43.5%; F = 42.3%), respiratory tract drugs (M = 29.0%; F = 26.1%), and hormones (M = 13.1%; F = 11.3%). Irrespective of gender, beclomethasone was the most utilized active substance in the first 2 years of life, while thereafter amoxicillin/clavulanate in combination.Conclusions: In a large population of pediatric outpatients no major difference was seen between genders, although commonly used drug classes; in particular, antibiotics, respiratory tract drugs and Hormones with corticosteroids for systemic use prescribed modestly but consistently to larger extent in males than females

Healthcare Database Networks for Drug Regulatory Policies: International Workshop on the Canadian, US and Spanish Experience and Future Steps for Italy

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Withdrawal Syndrome Following Discontinuation of 28 Antidepressants: Pharmacovigilance Analysis of 31,688 Reports from the WHO Spontaneous Reporting Database

Introduction: Evidence is lacking on withdrawal syndrome related to individual antidepressants and relevant risk factors for severe reactions. Objective: To ascertain whether antidepressants are associated with an increased reporting of withdrawal syndrome as compared with other medications, and to investigate risk factors for severe reactions. Methods: This is a case/non-case pharmacovigilance study, based on the VigiBase®, the WHO global database of individual case safety reports of suspected adverse drug reactions. We performed a disproportionality analysis of reports of antidepressant-related withdrawal syndrome (calculating reporting odds ratio [ROR] and Bayesian information component [IC]). We compared antidepressants to all other drugs, to buprenorphine (positive control), and to each other within each class of antidepressants (selective serotonin reuptake inhibitors [SSRIs], tricyclics and other antidepressants). Antidepressants with significant disproportionate reporting were ranked in terms of clinical priority. Serious versus non-serious reactions were compared. Results: There were 31,688 reports of antidepressant-related withdrawal syndrome were found. A disproportionate reporting was detected for 23 antidepressants. The estimated ROR for antidepressants altogether, compared to all other drugs, was 14.26 (95% CI 14.08-14.45), 17.01 for other antidepressants (95% CI 16.73-17.29), 13.65 for SSRIs (95% CI 13.41-13.90) and 2.8 for tricyclics (95% CI 2.59-3.02). Based on clinical priority ranking, the strongest disproportionate reporting was found for paroxetine, duloxetine, venlafaxine and desvenlafaxine, being comparable to buprenorphine. Withdrawal syndrome was reported as severe more often in males, adolescents, persons in polypharmacy, and with a longer antidepressant treatment duration (p < 0.05). Conclusions: Antidepressants are associated with an increased reporting of withdrawal syndrome compared with other drug classes. When prescribing and discontinuing antidepressants, clinicians should be aware of the potentially different proclivity of withdrawal syndrome across individual antidepressants, and the liability to experience more severe withdrawal symptoms in relation to specific patient characteristics

Antipsychotic drug use and community-acquired pneumonia

Antipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psy

How healthy is community-dwelling elderly population? Results from southern Italy

PURPOSE To explore the frequency of polypharmacy, functional and cognitive capacity among the elderly in Southern Italy. METHODS Populationbased retrospective cross-sectional study. Information were retrieved from electronic-geriatric-forms matched by record-linkage to outpatient pharmacy-records. The following domains were collected from geriatric forms: BMI, cognitive capacity (SPMSQ), functional status Barthel-index), mobility, living condition. Polypharmacy status was categorized as non-polypharmacy (0-4), polypharmacy (5-9) and excessive-polypharmacy (>10). Prevalence of all variables were stratified by age and polypharmacy group. RESULTS 88,878 old people received a geriatric assessment in the years 2013-2014. Mean age was 74.8 (±7.3) years, 56.6% females. Proportion of elderly in excessive-polypharmacy increased with age (18.9% in 65-75 age-group; 27.9% in >85). Referring to cognitive capacity, the proportion of lucid patients decreased with age (from 94.3% to 58.1%), while confused patient increased with age (from 4.7% to 30.9%). Proportion of subjects with a decline in cognitive status, functional status and mobility increased in polypharmacy and excessive polypharmacy group. CONCLUSION Polypharmacy is common in people aged 65 years and older with difficulties in activities of daily living and impaired cognition. Furthermore, its prevalence raises with increasing age. Preventive strategies such us optimization of drug regimen should be performed routinely to reduce risk of adverse-health-events