Identification of severe potential drug-drug interactions using an Italian general-practitioner database.

OBJECTIVE: To analyze prescriptions in a general-practitioner database over 1 year to determine the frequency, the characteristics, and the monitoring of the severe potential drug-drug interactions (DDIs). METHODS: We retrospectively analyzed the clinical records from 16 general practitioners in the Veneto region, an area in northern Italy. The study covered the period from January 1 to December 31, 2004. We selected all severe and well-documented interactions according to the book Drug Interaction Facts by David S. Tatro (Facts and Comparisons, St. Louis, MO, 2006). We grouped severe potential DDIs according to their specific potential risk, and for the most frequently interacting drug pairs, we investigated whether some specific tests had been prescribed by physicians for safety monitoring. RESULTS: During the study period, 16,037 patients (55% female) with at least one drug prescription were recorded, and a total of 185,704 prescriptions relating to 1,020 different drugs were analyzed. Ramipril was the most frequently prescribed drug followed by acetylsalicylic acid and atorvastatin. The final number of different types of severe potential DDIs was 119, which occurred 1,037 times in 758 patients (4.7% of the total number of patients). More than 80% of drugs involved in severe potential DDIs were cardiovascular drugs. Digoxin was the most frequently involved drug. Electrolyte disturbances, increase in serum digoxin levels, risk of hemorrhage, severe myopathy or rhabdomyolysis, and cardiac arrhythmias were the most commonly implicated potential risks. When considering patients using digoxin with loop or thiazide diuretics for more than 5 months, 72% had at least one test to monitor potential digoxin toxicity, whereas 28% had no tests. Sixty-four percent of patients using digoxin with amiodarone, verapamil, or propafenone had an ECG and/or digoxin monitoring, and 36% of them did not have any tests. CONCLUSIONS: The present study revealed that, in a group of Italian general practitioners, the risks of severe potential drug interactions are relatively low and the drugs concerned are few. Analyses of specific tests showed that physicians are generally aware of the potential risks caused by digoxin drug associations. However not all patients were closely monitored and this should be improved.

Use and safety profile of antiepileptic drugs in Italy.

OBJECTIVE: To analyse and discuss the use and the safety profile of individual antiepileptic drugs (AEDs) in Italy. METHODS: The AED safety data referred to the period January 1988-June 2005 and were obtained from the database of the Italian Interregional Group of Pharmacovigilance (GIF). This database collects all spontaneous reports of suspected adverse drug reactions (ADRs) from six Italian regions which are the main contributors to the Italian spontaneous reporting system. Individual AED consumption data (defined daily dose/1,000 inhabitants per day) in the GIF area and in the whole of Italy referred to the period January 2003-June 2005 and were derived from drug sales data (Institute for Medical Statistics Health). RESULTS: Phenobarbital was the most frequently used AED in the GIF area (4.26 DDD/1,000 inhabitants per day) followed by carbamazepine (1.97), valproic acid (1.33) and gabapentin (1.10). AED consumption in the whole of Italy showed a similar pattern. Gabapentin was the most frequently used AED among newer AEDs. In the GIF database 37,906 reports (up to June 2005) were present; 666 of them (1.76%) were associated with at least one AED (Anatomical Therapeutic Chemical code N03A). The AED with the highest number of reports was carbamazepine (208 reports) followed by phenobarbital (98), gabapentin (80), phenytoin (56), valproic acid (55), lamotrigine (51), oxcarbazepine (43) and vigabatrin (35). Use and toxicity profile were evaluated only for AEDs associated with at least 30 reports. Skin reactions were the most frequently reported ADRs, followed by haematological, general condition, hepatic, neurological and gastrointestinal adverse reactions. Phenobarbital, lamotrigine, carbamazepine and phenytoin had the highest percentage of skin reactions (69, 67, 60 and 54%, respectively). Many haematological reactions were reported for each AED; the highest percentage was related to valproic acid (25%). Vigabatrin was associated with the highest percentage of reactions related to hearing, vision and other senses (97%). Phenytoin and valproic acid had the highest percentage of hepatic reactions (30 and 20%), whereas gabapentin of nervous system, psychiatric, gastrointestinal and urinary reactions (26, 21, 21 and 14%, respectively) and phenobarbital of musculoskeletal reactions (13%). CONCLUSIONS: In Italy antiepileptic drug therapy appears to be still dominated by traditional drugs. Our analysis showed a different safety profile related to each AED. Some of the drug-adverse reaction associations discussed are not included in the Italian drug leaflets or have not been reported before in the literature.