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Introduction : The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 represents a serious health issue worldwide, with more than 61 million cases and more than 1.4 million death since the beginning of the epidemic near the end of 2019. The scientific community strongly responded to this emergency situation with massive research efforts, mostly focused on diagnosis and clinical investigation of therapeutic solutions. In this scenario, drug repurposing played a crucial role in accelerating advanced clinical testing and shortening the time to access the regulatory review. Areas covered : This review covers the main and most successful drug repurposing approaches from a design, clinical, and regulatory standpoint. Available patents on repurposed drugs are also discussed. Expert opinion : Drug repurposing proved highly successful in response to the current pandemic, with remdesivir becoming the first specific antiviral drug approved for the treatment of COVID-19. In parallel, a number of drugs such as corticosteroids and low molecular weight heparin (LMWH) are used to treat hospitalized COVID-19 patients, while clinical testing of additional therapeutic options is ongoing. It is reasonably expected that these research efforts will deliver optimized and specific therapeutic tools that will increase the preparedness of health systems to possible future epidemics.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297– 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a β-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Background To describe frequency, preventability and seriousness of adverse drug reactions (ADRs) in children as cause of emergency department (ED) admission and to evaluate the association between specific factors and the reporting of ADRs. Methods A retrospective analysis based on reports of suspected ADRs collected between January 1st, 2012 and December 31st, 2016 in the ED of Meyer Children’s Hospital (Italy). Demographics, clinical status, suspected drugs, ADR description, and its degree of seriousness were collected. Logistic regression was used to estimate the reporting odds ratios (RORs) with 95% confidence intervals (CIs) of potential predictors of ADR seriousness. Results Within 5 years, we observed 834 ADRs (1100 drug-ADR pairs), of whom 239 were serious; of them, 224 led to hospitalization. Patients were mostly treated with one drug. Among patients treated with more than one drug, 78 ADRs presented a potential interaction. The most frequently reported ADRs involved gastrointestinal system. The most frequently reported medication class was antinfectives. Risk of serious ADR was significantly lower in children and infants compared to adolescents (ROR 0.41 [95% CI: 0.27–0.61] and 0.47 [0.32–0.71], respectively), and it was significantly increased in subjects exposed to more than one drug (ROR 1.87 [1.33–2.62] and 3.01 [2.07–4.37] for subjects exposed to 2 and 3 or more drugs, respectively). Gender, interactions and off-label drug use did not influence the risk of serious ADRs. Conclusion Active surveillance in pharmacovigilance might represent the best strategy to estimate and characterize the clinical burden of ADRs in children. Electronic supplementary material The online version of this article (10.1186/s40360-018-0207-4) contains supplementary material, which is available to authorized users.

Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. This study evaluated safety and efficacy of propranolol eye micro-drops in preterm newborns with ROP. A multicenter open-label trial, planned according to the Simon optimal two-stage design, was performed to analyze safety and efficacy of propranolol micro-drops in newborns with stage 2 ROP. To this end, hemodynamic and respiratory parameters were monitored, and blood samples were collected weekly, for 3 wk. Propranolol plasma levels were also monitored. The progression of the disease was evaluated with serial ophthalmologic examinations. Twenty-three newborns were enrolled. Since the fourth of the first 19 newborns enrolled in the first stage of the study showed a progression to stage 2 or 3 with plus, the second stage was prematurely discontinued. Even though the objective to complete the second stage was not achieved, the percentage of ROP progression (26%) was similar to that obtained previously with oral propranolol administration. However, no adverse effects were observed and propranolol plasma levels were significantly lower than those measured after oral administration. Propranolol 0.1% eye micro-drops are well tolerated, but not sufficiently effective. Further studies are required to identify the optimal dose and administration schedule.

Summary What is known and Objective: Methotrexate (MTX) is widely used in the management of paediatric cancer with a generally favourable benefit/risk profile. We report an unusual adverse drug reaction with the first course of high-dose MTX in a paediatric patient and review the literature for similar cases. Case summary: An 11-year-old boy with small-cell osteoblastic osteosarcoma in the lower limb experienced a case of life-threatening anaphylaxis during the first course of high-dose MTX. The adverse event occurred during the first course, likely due to an immune-mediated mechanism. We postulate that prior antineoplastic treatment might have contributed to the immune response to MTX. What is new and Conclusion: Given that this reaction has rarely been reported, we discuss the present case with a review of other similar cases. Further studies are needed to substantiate this ‘signal alarm’ for serious MTX-related hypersensitivity reactions.

Objective To verify whether vaccination against the A-H1N1 virus in the paediatric population was effective in preventing the occurrence of influenza-like illness (ILI) or was associated with adverse events of special interest. Design, setting and patients A case–control analysis was performed as part of surveillance of children hospitalised through the emergency departments of eight paediatric hospitals/wards for ILI, neurological disorders, non-infectious muco-cutaneous diseases and vasculitis, thrombocytopaenia and gastroduodenal lesions. Results Among 736 children enrolled from November 2009 to August 2010, only 25 had been vaccinated with the pandemic vaccine. Out of 268 children admitted for a diagnosis compatible with the adverse events of special interest, six had received the A-H1N1 vaccine, although none of the adverse events occurred within the predefined risk windows. Only 35 children out of 244 admitted with a diagnosis of ILI underwent laboratory testing: 11 were positive and 24 negative for the A-H1N1 virus. None of the A-H1N1 positive children had received the pandemic vaccine. The OR of ILI associated with any influenza vaccination was 0.9 (95% CI 0.1 to 5.5). Conclusions The study provides additional information on the benefit–risk profile of the pandemic vaccine. No sign of risk associated with the influenza A-H1N1 vaccine used in Italy was found, although several limitations were observed: in Italy, pandemic vaccination coverage was low, the epidemic was almost over by mid December 2009 and the A-H1N1 laboratory test was performed only during the epidemic phase (in, Article summary Article focus To assess the effectiveness of the influenza A-H1N1 vaccine and the occurrence of adverse events of special interest in the paediatric population. Key messages During the 2009–2010 influenza season, very limited information was available on the safety and effectiveness of the influenza A-H1N1 vaccine. Together with other post-marketing studies, our findings provide additional information on the benefit–risk profile of the pandemic vaccine. Strengths and limitations of this study The study focused on influenza-like illness and adverse events of special interest that were sufficiently severe to cause hospitalisation in children and provided additional information on the benefit–risk profile of the pandemic vaccine. A-H1N1 vaccination coverage in Italy during the 2009–2010 influenza season was very low, with around 4% of the general population and only 3.7% of the children included in this study having been vaccinated. The influenza outbreak was almost over by the first half of December 2009, and both the incidence and severity of the disease were lower than expected.

Background Vernal Keratoconjunctivitis (VKC) is an allergic conjunctivitis, often not easily diagnosed and properly treated. The disease is very debilitating for patients, may be complicated by corneal lesions and can evolve to keratoconus. Purpose The exponential increase in VKC patients led us to start a close collaboration between pharmacists and allergists, ophthalmologists, and chemists. The goal was to address and solve problems caused by the lack of adequate knowledge of VKC, in order to find a diagnostic-therapeutic course, improve patient compliance and provide high-quality products as an alternative to conventional treatments. Material and methods After discussions with allergists and ophthalmologists, pharmacists formulated 3 different kinds of eye drops as treatment: ciclosporin 1% and tacrolimus 0.1%, both in methylcellulose 0.15%, and ciclosporin 2% in sunflower oil. The stability of such formulations was demonstrated by using liquid chromatography coupled to a triple quadrupole mass spectrometer. The pharmacist now prepares a weekly supply of eye drops, after allergists pass on the number of children who will undergo eye examinations. Then, the pharmacist proceeds, after allergist confirmation, to arrange for eye drops to be sent directly to patients’ homes in the whole country. Results The LC/MS/MS and sterility analysis results allowed the pharmacist to declare that formulations in methylcellulose 0.15% and in sunflower oil were safe for up to 45 days. Such formulations were chosen considering also patient compliance. Indeed, one of the results of the team collaboration has been the development of the formulation in sunflower oil, which can be stored at room temperature; thus leading to huge advantages in terms of patient compliance. Conclusion The preparation of a galenical formulation of such quality has contributed to the efficacy of the treatment. Moreover, the sharing of information between medical doctors, pharmacists and nurses has led to personalised assistance that is highly responsive to health needs. Reference Leonardi A. Prog Retin Eye Res 2002;21(3):319–39 No conflict of interest.