Eudiana Vale Francelino

Presença de excipientes com potencial para indução de reações adversas em medicamentos comercializados no Brasil

Pharmaceutical excipients can be responsible for many ADR. The objectives of this study were to identify the presence of possible excipients as cause of ADR in drugs commercialized in Brazil. Twelve medicines with high indices of sales in Brazil, were selected to analysis. The bibliographic research about the Pharmaceutical Preparations (PP) was carried from August to September/04. The sources of information used were Pharmaceutical Specialties Dictionary, web sites and customer services from the manufacturers and technical files of the National Agency of Sanitary Vigilance. The excipients were detected as a whole and also the compounds that may cause adverse reactions and its risks to the health. They were identified 35 PP. Of these, 26 were classified as Over-The-Counter medicines (OTC) (71.4%) and 15 of paediatric use (42.8%). Between the excipients identified (n=100), 9 were possible causes of ADR: metylparaben, propylparaben, yellow dye tartrazine, sodium bissulfit, sodium benzoate, lactose, benzalkonium chloride, sorbitol and benzilic alcohol, being identified in 7 use in paediatric (19.0%) and 12 of OTC (32.4%). The results shows the need of more attention from the health professionals, the patient and the development of evaluation by the pharmacovigilance systems, of the presence of excipients as possible inductors of ADR.

Reações adversas causadas por fármacos que atuam no sistema nervoso: análise de registros de um centro de farmacovigilância do Brasil

BACKGROUND: The morbi-mortality by the use of medicines is a major health problem. The drug adverse reactions may result in death, increased hospitalizations and healthcare costs. OBJECTIVES: Describe and analyze reports of suspected adverse reactions caused by drugs that act on the nervous system (SN-ADR), registered in the database of the Pharmacovigilance Centre of Ceara, from January 1997 to March 2008. METHODS: All the NS-ADRs were classified according to criteria of the World Health Organization. The causality between the drug administered and the adverse reaction was established, as well as the analysis regarding to the severity of the reaction. RESULTS: The Centre recorded 176 notifications of RAM-SN. The most of the reactions occurred in the hospital. The main reporter was the pharmacist. All the RAM-SN were classified as possible (n = 110), probable (n = 37) and definite (n = 17). With regard to severity, the NS-ADRs were considered: light (n = 21), moderate (n = 127), serious (n = 15) and fatal (n = 1). The fatal case was reported by physician, and involved anesthetic drugs. In general the adverse reactions observed were caused predominantly by analgesics, anesthetics and antiepileptics. DISCUSSION: The data demonstrate the potential values of accessing to a local system of pharmacovigilance to report possible risks with the use of nervous system drugs.CONTEXTO: A morbimortalidade por uso de medicamentos e um grande problema de saude. As reacoes adversas a medicamentos podem resultar em obito, aumento de internacoes hospitalares e dos custos com a saude. OBJETIVOS: Descrever e analisar as notificacoes de suspeitas de reacoes adversas causadas por medicamentos que atuam no sistema nervoso (RAM-SN), registradas no Centro de Farmacovigilância do Ceara, de janeiro de 1997 a marco de 2008. METODOS: As RAM-SN foram classificadas segundo os criterios da Organizacao Mundial da Saude. Uma relacao de causalidade entre o farmaco administrado e a reacao adversa identificada foi realizada, bem como a analise da reacao quanto a gravidade. RESULTADOS: Foram registradas 176 notificacoes de RAM-SN. A maioria (n = 145; 82,4%) ocorreu no ambiente hospitalar. O principal notificador foi o farmaceutico. As RAM-SN foram classificadas como: possiveis (n = 110), provaveis (n = 37) e definidas (n = 17). Quanto a gravidade, foram consideradas: leves (n = 21), moderadas (n = 127), graves (n = 15) e fatais (n = 1). O caso fatal foi notificado por medico e envolveu medicamentos anestesicos. Geralmente, as reacoes adversas observadas foram causadas predominantemente por analgesicos, anestesicos e antiepilepticos. DISCUSSAO: Os dados demonstram o valor potencial de se ter acesso a sistemas de farmacovigilância local para registrar possiveis riscos com o uso de farmacos.

Polymorphism of IL10, IL4, CTLA4, and DAO Genes in Cross‐Reactive Nonsteroidal Anti‐inflammatory Drug Hypersensitivity

Our aim was to evaluate genetic polymorphism of molecules involved in immunoregulatory/allergic processes in patients who presented with cutaneous hypersensitivity caused by chemically unrelated nonsteroidal anti‐inflammatory drugs. Polymorphisms at IL10 (–1082 G>A), IL4 (–589 C>T), CTLA4 (+49A>G), and DAO (+8956 C>G) genes were studied in 55 cases and 97 controls by the polymerase chain reaction‐restriction fragment length polymorphism technique. With regard to the polymorphism at IL10 –1082, higher frequencies of the AG genotype (57% vs 39%) and G allele carriers (70% vs 48%) were found among the patients, indicating a risk effect (odds ratio [OR] = 2.56 and P = .01 for AG genotype and OR = 2.52; P = .01 for AG/GG). For the CTLA4 +49 A/G single‐nucleotide polymorphism (SNP), AG genotype (31.0%) (P = .02) and G carrier (54.0%) (P = .05) frequencies were found to be significantly lower in the patient group compared with the control group (51.0% and 69.0%, respectively). The SNP DAO +8956 C>G was associated with a strong protective effect, with OR values of 0.83 for CG and 0.11 for GG genotype (P = .04 for the codominant model), suggesting an allele dose effect. The combination of IL10 and DAO SNPs in a multivariate model did not alter the OR values, suggesting independent effects for both SNPs. The results are striking. In conclusion, these results suggest that polymorphisms in regulatory targets of the immune response and in DAO gene could modulate an individuals susceptibility to nonsteroidal anti‐inflammatory drug hypersensitivity reactions. Further studies will be necessary to complement our results.

Acute Generalized Exanthematous Pustulosis in a 51-Year-Old Patient under Etanercept Treatment for Psoriasis

Acute generalized exanthematous pustulosis (AGEP) is a cutaneous reaction mostly related to drug, which is characterized by a rapid appearance of fever, erythema, sterile pustules and neutrophilia. We report a 51-year-old female patient who had taken etanercept 50 mg/week for treatment of psoriasis. In the third month of pharmacotherapy, she interrupted the treatment on her own, and consequently, the lesions reappeared. When the drug was reintroduced, it was associated with prednisone 40 mg/day during 5 days. After this period, multiple erythematous and edematous lesions appeared with small non-follicular pustules. Oral corticosteroid was administered and a progressive and complete improvement was achieved. Histopathological findings revealed AGEP. Bacterioscopy of the pustules proved negative. The patient obtained the score 12 according to the EuroSCAR study group, which indicated a definitive diagnosis of AGEP. The criteria for diagnosis were based on morphology, course and histology of the skin reaction. The association between Etanercept and AGEP is an uncommon finding in the literature.

Ações de Farmacovigilância no Nordeste do Brasil: uma análise de 10 anos de trabalho em prol da segurança no uso de medicamentos

Pharmacovigilance in the Northeast of Brazil: an analysis of 10 years of work in favor of safety in the use of medicines