Spontaneous reporting of drug-related hepatic reactions from two Italian regions (Lombardy and Veneto).

BACKGROUND AND AIMS: Many currently used drugs are implicated in liver disorders ranging from asymptomatic abnormal liver function tests to fatal liver failure, and drug-induced hepatic reactions are the most frequent cause of the withdrawal of drugs from the market in the United States, United Kingdom and Spain. The aim of this study was to review the drug-induced hepatic reactions notified to the spontaneous surveillance system of two Italian regions (Lombardy and the Veneto) up to 31 December 1998. PATIENTS AND METHODS: The reports of hepatic adverse drug reactions were extracted from an inter-regional database of spontaneous adverse drug reaction reports and analysed by reporter category, patient age and sex, the underlying disease, the adverse reaction and drug exposure. In the case of drugs involved in more than four reports, a search was made of the Medline, Hepatox, Micromedex and WHO databases. RESULTS: Between 1988 and 1998, there were 310 reports of hepatic lesions associated with single drugs or fixed combinations, the most frequently involved patient categories being females and the elderly. Sixty percent of the reactions were classified as serious, with three fatal cases. Thirteen drugs were associated with more than four reports and accounted for 35% of all of the hepatic reactions. Six drugs not known as hepatotoxic agents were associated with hepatic reactions. CONCLUSIONS: In this study, spontaneous reports have suggested previously unknown hepatotoxicty of six drugs, and have improved drug safety profiles as shown in an Italian inter-regional health service.

Nimesulide and renal impairment.

OBJECTIVES: To analyse from spontaneous reporting data the renal adverse reactions associated with the use of nimesulide. METHODS: Case reports were obtained from a Northern Italian Regional database (Veneto Pharmacovigilance System), containing all the spontaneous reports filed between 1988 and 1997. The Veneto Region is the principal contributor to the Italian spontaneous reporting system, with an annual report rate of approximately 17 per 100,000 inhabitants. The clinical records of hospitalized patients were also analysed. RESULTS: Of the 120 reports associated with oral nimesulide, 11 referred to suspected renal adverse reactions. The drug was taken by ten patients for a short period. All the patients discontinued the therapy and hospitalization was required in six cases. Other risk factors were identified in six cases. DISCUSSION: Together with the new insights into the possible consequences of renal cyclooxygenase-2 (COX-2) inhibition, the reported cases should draw the attention of doctors and patients to the importance of recognizing any possible signs of renal impairment during nimesulide therapy, although only extensive epidemiological data can define the real impact of its renal toxicity.

Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions.

AIMS: Cutaneous manifestations are frequently reported in association with drug use. The aim of this study was to analyse the skin reactions reported to the spontaneous surveillance systems of four Italian regions (Friuli Venezia Giulia, Lombardy, Sicily and the Veneto), and correlate the reports with estimated drug consumption during the same period, paying particular attention to the reactions to antimicrobial agents and nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: All of the adverse drug reactions (ADRs) reported spontaneously between January 1996 and December 1997 to the surveillance systems of four Italian regions (a total population of about 20 million people) were analysed by a panel of experts including dermatologists. On the basis of the Critical Term List of the World Health Organization (WHO), the reactions were classified as either serious or nonserious events. Drug consumption was expressed as a daily defined dose (DDD)/1000 inhabitants/day. RESULTS: A total of 2224 adverse skin reaction reports (44.7% of all of the reported ADRs) were identified, making a reporting rate of about 5.5 per 100 000 inhabitants/year. The female/male ratio was 1.58, and the reporting rate progressively increased with age. The drug categories with the highest number of cutaneous reactions were antimicrobials, followed by NSAIDs, analgesics and radiology contrast media. There was a total of 372 (16.9%) serious reaction reports, the most frequent being angioedema (171 cases), erythema multiforme (68 cases) and photosensitivity (37 cases). Co-trimoxazole, followed by the cephalosporins and fluoroquinolones, were associated with the highest consumption-related reporting rate among the antimicrobials, and aspirin and dipyrone among the NSAIDs and analgesics. CONCLUSIONS: Spontaneous reports from four Italian regions revealed that the skin was the organ most frequently affected by ADRs. The paper shows the validity of a regional decentralized system in Italy.