PURPOSE. The study aimed at assessing if the European guideline on the use of antihypertensive drugs (AD) in pregnancy are followed in clinical practice. We also evaluated the association between the use of non-recommended drugs and individual characteristics. METHODS. This study analyzed a cohort of 86 171 singleton deliveries occurring between 2009-2010 in the Lombardy region, Italy. Women with first prescription of AD during pregnancy were considered as incident users. Methyldopa, labetalol and nifedipine were considered as "recommended drugs"; all other AD were considered as "non-recommended". Odds Ratio and 95% confidence intervals were estimated. RESULTS. Among the 1009 patients (1.2%) exposed to AD during pregnancy, 675 (66.9%) were incident users. Among the incident users, 31% received non-recommended drugs; this proportion decreased to 18% among women who started treatment in the third trimester. Women with at least four concomitant diseases had an elevated risk of receiving non-recommended drugs in pregnancy (OR 2.68; 95% CI 1.10-6.73). CONCLUSIONS. Exposure to recommended antihypertensives increased during pregnancy. Nevertheless, a fraction of users that continued or began treatment with non-recommended medications was still present.

INTRODUCTION: The possibility that variation in packaging and pill appearance may reduce adherence is a reason for concern, especially for chronic diseases. The objectives of the study were to quantify the extent of switches between generic antidiabetics and to verify whether switching between different products of the same substance affects adherence. MATERIALS AND METHODS: All elderly residents of the Umbria Region who received at least 2 prescriptions of antidiabetics in 2010 and 2011 were included in the study. Switching was defined as the dispensing of two different products of the same substance in a series of two prescriptions. Single and multiple switchers were identified according to the number of switches during 2011. Switching relevant to the three off-patent substances with generic use ≥ 5% (metformin, gliclazide and repaglinide) was quantified. The effect of switching on adherence, defined as the proportion of days in 2011 covered by prescriptions (Medication Possession Ratio, MPR), was estimated. RESULTS: Among the 15 964 patients receiving antidiabetics (14.4% of the elderly population) 9211 were prescribed at least one of the generic substances. Of these patients, 23.3% experienced a single switch and 15.7% were multiple switchers (61.0% never switched). The proportion of multiple switchers increased with the number of prescriptions, reaching 26% among patients with ≥ 11 prescriptions. MPR was 62%, 62% and 72%, respectively among non-switchers, single and multiple switchers. CONCLUSIONS: In elderly patients treated with antidiabetics, the substitution between branded and unbranded products (as well as between generics) of the same substance, did not negatively affect adherence.

In 2002 and 2007 the European Medicines Agency (EMA) examined the signals of a greater risk of hepatopathies related to nimesulide use. In 2007 restrictive actions were adopted in Europe. Moreover, EMA initiated a new referral in February 2010. The objective of this paper is to evaluate the effects of the 2007 regulatory measures concerning nimesulide and to estimate the potential effect of further actions. Specifically, we carried out a simulation on the expected number of hospitalisations for hepatopathies and upper gastrointestinal bleedings (UGIBs) in Italy before and after the regulatory measures (2006 vs. 2009), taking into account the shifting of nimesulide prescriptions on other non steroidal anti-inflammatory drugs (NSAIDs). The expected figures of hospitalisation for hepatopathies and UGIBs for all NSAIDs were calculated on the basis of risk estimates reported in two epidemiological studies. The result of the simulation suggests that the implementation of the restrictive actions might prevent 79 events of liver injuries, but might increase UGIBs by 859 events. The simulation helped to clarify the effects on hepatopathies and UGIBs as a consequence of nimesulide restriction of use. Analogous simulations might be conducted when assuming regulatory actions.

Nel 2002 e nel 2007 l'Agenzia Europea dei Medicinali (EMA) ha valutato un segnale di rischio di epatopatie associato all'uso di nimesulide. Nel 2007 sono state adottate misure restrittive nella prescrizione del farmaco in Europa. Nel febbraio 2010 l'EMA ha aperto una nuova procedura di arbitrato. Obiettivo del lavoro è valutare l'effetto delle misure restrittive della prescrizione di nimesulide e di ulteriori possibili misure regolatorie. Attraverso una simulazione è stato stimato il numero atteso di ospedalizzazioni per epatopatie e per sanguinamenti gastroduodenali (UGIB) in Italia, nel 2006 e 2009, tenendo conto di un possibile spostamento delle prescrizioni di nimesulide verso altri farmaci antinfiammatori non steroidei (FANS). La frequenza attesa di ospedalizzazione, prima e dopo le misure restrittive, è stata calcolata in base ai dati di due studi epidemiologici. I risultati suggeriscono che l'implementazione delle azioni regolatorie riguardanti la nimesulide potrebbe avere evitato 79 ricoveri per danno epatico, ma avere incrementato i ricoveri per UGIB di 859 casi. La simulazione contribuisce a chiarire gli effetti su epatopatie e sanguinamenti gastroduodenali come conseguenza delle misure restrittive nella prescrizione di nimesulide. Valutazioni simili dovrebbero essere condotte quando si adottano misure limitative nell'uso di farmaci.