Introduction:Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010.Materials and Methods:We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs.Results:A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar®), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups “41-65” (39.07%) and “over 65” (27.9%) were the most affected.Conclusions:Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

Introduction:The epidermal growth factor receptor inhibitors (EGFRIs), cetuximab and panitumumab, represent an effective treatment option for patients affected by metastatic colorectal cancer (mCRC); furthermore, they are relatively devoid of systemic toxicities, which are commonly observed with standard cytotoxic chemotherapy. However, the majority of patients treated with these monoclonal antibodies (mAbs), will experience dermatologic toxicities, most notably the papulopustular skin rash, which can impact quality-of-life and affect adherence to therapy. This paper reviews the most recent practices in the management of skin rash related to anti-epidermal growth factor receptor (EGFR) mAbs, cetuximab and panitumumab, in the treatment of mCRC.Materials and Methods:We reviewed relevant literature regarding dermatologic toxicities associated with anti-EGFR mAbs in order to give important indications about prevention and reactive treatment of skin rash.Results:Two case reports were presented to show how skin rash could hamper mAb EGFRIs use in clinical practice, underscoring the need of implementing a comprehensive management strategy of skin toxicity in order to promote patients’ compliance with anti-EGFR therapy and maintain quality-of-life. Based on randomized data, recent guidelines established by the Multinational Association for Supportive Care in Cancer Skin Toxicity Study Group suggest that prophylactic use of oral doxycycline or minocycline reduces the risk and severity of skin rash, improving clinical outcomes.Conclusions:At the start of treatment with cetuximab and panitumumab, the proper patient education about the skin rash associated with these mAbs and the implementation of a pre-emptive, comprehensive skin toxicity program significantly contribute to improve adherence to therapy, optimize anti-EGFR therapy and maintain quality-of-life.

Trabectedin (Yondelis(®)) is a potent marine-derived antineoplastic drug with high activity against various soft tissue sarcoma (STS) subtypes as monotherapy, and in combination with pegylated liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum-sensitive ovarian cancer. This article reviews the safety and pharmacokinetic profiles of trabectedin. Records were identified using predefined search criteria using electronic databases (e.g. PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published between 1 January 2006 and 1 April 2014 were included. The current safety and tolerability profile of trabectedin, based on the evaluation in clinical trials of patients treated with the recommended treatment regimens for STS and recurrent ovarian cancer, was reviewed. Trabectedin as monotherapy or in combination with PLD, was not associated with cumulative and/or irreversible toxicities, such as cardiac, pulmonary, renal, or oto-toxicities, often observed with other common chemotherapeutic agents. The most common adverse drug reactions (ADRs) were myelosuppression and transient hepatic transaminase increases that were usually not clinically relevant. However, trabectedin administration should be avoided in patients with severe hepatic impairment. Serious and fatal ADRs were likely to be related to pre-existing conditions. Doxorubicin or PLD, carboplatin, gemcitabine, or paclitaxel when administered before trabectedin, did not seem to influence its pharmacokinetics. Cytochrome P450 (CYP) 3A4 has an important role in the metabolism of trabectedin, suggesting a risk of drug-drug interactions with trabectedin used in combination with other CYP3A4 substrates. Trabectedin has a favorable risk/efficacy profile, even during extended treatment in pretreated patients.

Off-label use is very common among pediatricians, and the main cause is attributable to the lack of drugs specifically designed and marketed for children in different age groups. In this study, we evaluated, through a questionnaire, the knowledge of off-label drugs in pediatrics. Furthermore, we made a directory of 28 off-label drugs most commonly used by pediatricians in agreement with data obtained from Italian Agency for drugs (AIFA) referred to the law no. 648/1996; 180 pediatricians referred to the Italian Society of Pediatrics Calabrian section were asked to complete an online anonymous questionnaire. Eighty five (47.3%) of these completed the anonymous questionnaire, 40% revealed that they used off-label drugs “sometimes”; generally, drugs were used off-label for age and to treat respiratory diseases. For 75 pediatricians (88%) the information about the risk/benefit of off-label drugs is inadequate and 63 pediatricians (74%) did not have a good knowledge about this practice. In conclusion, the knowledge of off-label drugs is very low in pediatricians; more information about off-label drugs could be useful in order to improve the appropriateness of drugs’ prescription and to reduce the development of side effects and improving drug safety.

were intercepted prior to administration to the patient. Wrong dose represented the most common type of error. Few pharmaceutical errors (transcription, validation, preparation) were detected. No conflict of interest.

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Adverse Drug Reactions (ADRs) are a serious health related problem, which can limit the treatment options, compliance and even leads to discontinuation of therapy. Unfortunately not in all countries, the reporting reaches standard levels set by the WHO. As well, in our region (Calabria), located in south of Italy, only few reports are usually reported. For these reasons, the Italian Agency of the Drugs (AIFA) has been promoting and financing regional projects with multidisciplinary groups to increase spontaneous reporting. From first January 2018, we started a survey program finalized to report all adverse events from antihypertensive drugs observed in our Cardiovascular Prevention Clinic. We evaluated all of the 250 outpatients (≥18 years), consecutively visited in our clinic, from 1 January 2018 to 30 April 2018. All of these were in antihypertensive treatment (monotherapy or multiple drugs therapy). A total of 20 ADRs were observed. Of the 20 ADRs, 19 were non-serious events; a serious event required hospitalization (atrial-ventricular complete block). Causality assessment has been estimated with the Naranjo algorithm; the results indicated n=19 possible ADRs and n=1 probable. Incidence of ADRs was found to be higher in the age group between 45 and 54 years old (6 of 20) and males experienced more ADRs than females (35%, 7 of 20). ADRs were more frequently associated with combination therapy (65%, 13 of 20) versus monotherapy. Calcium channel-blockers were found to be the most frequently associated drugs with ADRs (n=8), followed by angiotensin receptor blockers (n=4). We compared our reports with the reports, of the same period, available for our region obtained from National Pharmacovigilance Network. During this period were reported 27 side effect reactions in all our region (5 reports in the 2017). In conclusion, in the last 4 months, regional projects, with the creation of a multidisciplinary group composed of Medical and Pharmacists Facilitator, was useful in improving and increase quality and quantity of spontaneous reports in Calabria.