Safety of fexofenadine and other second-generation oral antihistamines before and after the removal of the prescription requirement in Italy and other European countries: A real-world evidence study and systematic review.

Background: The change from prescription to over-the-counter (OTC) status of oral antihistamines may raise concerns about drug safety due to the possibility of misuse/abuse. In most European countries, oral antihistamines are available without prescription, whereas in Italy, only <10-tablet packs are available OTC. Objectives: To evaluate the safety profile of fexofenadine after OTC switch in Italy in a real-world setting, and to compare its safety profile to that of other European countries where larger pack sizes are available. To compare the safety of fexofenadine, cetirizine, and loratadine in Italy. To examine safety/efficacy across Europe with a systematic review. Methods: This case-by-case analysis used the US Food and Drug Administration (FDA) adverse event reporting system (FAERS) to extract data of the adverse events (AEs) related to fexofenadine, loratadine and cetirizine in Italy January 2010-June 2020. The year 2016 was taken as the index date (removal of prescription requirement) for evaluation of the reporting trend of AEs of fexofenadine in Italy and make a comparison pre/post-OTC switch. A comparison of AEs with other European countries where fexofenadine is sold OTC in large packs >20 tablets (Belgium, Portugal, Switzerland, Finland, Hungary) was made. The rate at which an AE related to oral antihistamines occurred was estimated by calculation of the reporting rate (number of cases/[defined daily dose/1000 inhabitants per day]) on the basis of IQVIA sales data using the Italian Institute of Statistics database. A systematic review of the literature was also performed. Results: There were 3760 reports of AEs with a suspected association with fexofenadine; of these, eight were reported from Italy. There was a slightly increasing trend per year, in line with a general reporting trend of other drugs. In European countries where fexofenadine is available, the impact of OTC switch on AE reporting activity was negligible: from 2016, the reporting rate increased slightly and then normalized at 3.01, an incidence value similar to that recorded before the OTC switch (3.7 in 2015). Of 22 studies included in the systematic review, 18 (82%) positively evaluated the OTC use of oral antihistamines, confirming an acceptable safety/tolerability profile. Conclusion: There was no difference in number of AEs reported for fexofenadine pre/post-OTC switch, indicating a similar safety profile. Spontaneous reporting systems are a valuable source of real-world data and support the OTC provision of oral antihistamines in Europe and fexofenadine in Italy, in addition to supporting the use of larger pack sizes in Italy.

Effect of chronic venous insufficiency on activities of daily living and quality of life: correlation of demographic factors with duplex ultrasonography findings.

The study evaluates to what extent symptoms of chronic venous insufficiency (CVI) and functional venous incompetence as investigated using color-coded duplex ultrasonography may interfere with activities of daily living (ADLs). This study comprises a cross-sectional survey conducted in urban areas surrounding 24 Italian cities. A spontaneous sample of 5,187 subjects (4,457 women [mean age, 54 years] and 730 men [mean age, 61 years]), selected by advertising on television and in newspapers, underwent a clinical examination that included duplex ultrasonography in 3 vein segments in both legs to determine the presence and severity of venous reflux. Subjective perception of lower limb symptoms of CVI and the effect of leg problems on the ability to perform normal ADLs are assessed by means of a self-administered questionnaire. Most of the respondents have some CVI symptoms, with women being 1.5 to 3 times as likely as men to report leg symptoms. The risk of developing the most frequent subjective symptoms such as heaviness and tiredness in the legs is not statistically significantly different for younger subjects compared with older subjects. Advanced age is considered to be a relevant risk factor only for heat sensation and swollen legs. Persons living in southern Italy are at higher risk of almost all lower limb symptoms. Results of duplex ultrasonography performed on 3875 subjects show that fewer than 1 in 5 young persons, regardless of sex, manifest some degree of venous reflux (primarily mild symptoms). The risk of developing venous incompetence increases rapidly with age until it triples among subjects 50 years and older. Adjusting for all other factors, men are on average 1.5 times as likely as childless women to have venous reflux, and the risk increases in the case of family history of CVI or (among women) in the case of past pregnancies. More women than men report that their leg problems affect their ADLs. Pregnancy and living in the south contribute to a reduction in the ability to perform most heavy housework. Although milder lower limb symptoms such as evening heaviness and tiredness in the legs may begin early in life, venous reflux and related symptoms of heat sensation and swollen legs become more pronounced with age, and their severity can be disabling for those afflicted.

Chronic venous disorders: correlation between visible signs, symptoms, and presence of functional disease.

BACKGROUND: The aim of this study was to investigate the frequency of chronic venous disorders (CVD) in different demographic groups in Italy and to provide correlations between patterns of valve incompetence and clinical feature of disease severity. METHODS: Advertisements in television and newspapers in 53 Italian cities were used to solicit 16,251 subjects (13,826 women, mean age 50.4 years; 2,425 men, mean age 59.1 years). They underwent a clinical examination of the lower limbs, including presence and severity of visible signs (CEAP classification), and assessment of functional disease by color-coded duplex ultrasound imaging. RESULTS: Varicose veins and telangiectases were the most common objective signs in both men and women. Older people were more severely affected. Telangiectases were more frequent in women, and men had a higher incidence of trunk varices, trophic changes, and venous reflux. Frequency of both visible and functional venous disease increased with family history and body mass index. Presence of reflux correlated positively with increasing CEAP grade of visible disease (Pfor trend < .0001 for all superficial venous segments). A large number of subjects, especially women, complained of subjective symptoms in the legs, and the presence of symptoms correlated almost always positively with both worsening of visible findings (P for trend < .001) and presence of hemodynamic change in both genders. CONCLUSIONS: The frequency of reflux increased with the severity of visible signs of disease as described by the CEAP classification. In men, the occurrence of subjective symptoms was mostly correlated with functional disorders.