Drug-induced anaemia: a decade review of reporting to the Italian Pharmacovigilance data-base.

BACKGROUND: Studies investigating drug-induced anaemia are relatively scarce and mostly related to specific drugs or patients with specific pathologies. OBJECTIVE: To analyse all reports of suspected drug-induced anaemias recorded in the National Pharmacovigilance Database of the Italian Medicines Agency. METHOD: The cases of suspected drug-induced anaemias analysed were those retrieved from the Italian National Pharmacovigilance Database from January 2001 to December 2013. RESULTS: The active substances involved were 375 in 3,305 reports of drug-induced anaemia; of these, 72 % were reported as serious. In 35 % of the reports patients were in polytherapy. In 24.3 % of the cases relevant DDIs were identified. We found a PRR value of 57.29 for peginterferon alfa-2a, of 12.57 for ribavirin, of 13 for flu vaccine for the occurrence of autoimmune haemolytic anaemia. The drugs mostly involved in the cases where the Naranjo causality was probable or possible were acetylsalicylic acid, warfarin, ribavirin, peginterferon alfa-2a, carboplatin and acenocoumarol. CONCLUSIONS: A possible signal was detected for peginterferon alfa-2a, ribavirin and flu vaccine in the occurrence of autoimmune haemolytic anaemia. A great involvement of clopidogrel, enoxaparin, warfarin, ticlopidine and acetylsalicylic acid in preventable DDI-induced anaemia was detected, highlighting a poor awareness among healthcare providers on this issue.

On the relationship between human papilloma virus vaccine and autoimmune diseases.

The human papilloma virus (HPV) vaccines were introduced to reduce the incidence of cervical cancer. The bivalent vaccine is effective against HPV-16, -18, -31, -33 and -45 while the quadrivalent vaccine is effective against HPV-16, 18, 31, 6 and 11 types. The immunisation, recommended for adolescent females, has led to high vaccine coverage in many countries. Along with the introduction of the HPV vaccines, several cases of onset or exacerbations of autoimmune diseases following the vaccine shot have been reported in the literature and pharmacovigilance databases, triggering concerns about its safety. This vaccination programme, however, has been introduced in a population that is at high risk for the onset of autoimmune diseases, making it difficult to assess the role of HPV vaccine in these cases and no conclusive studies have been reported thus far. We have thus analysed and reviewed comprehensively all case reports and studies dealing with either the onset of an autoimmune disease in vaccinated subject or the safety in patients with autoimmune diseases to define the role of the HPV vaccines in these diseases and hence its safety. A solid evidence of causal relationship was provided in few cases in the examined studies, and the risk vs. benefit of vaccination is still to be solved. The on-going vigilance for the safety of this vaccine remains thus of paramount importance.

The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.

OBJECTIVE: To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). RESEARCH DESIGN AND METHODS: Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. RESULTS: We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. CONCLUSIONS: The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.