Aim: Chirality of drugs might be associated with safety issues through pharmacokinetic or pharmacodynamic variations, interactions, or direct toxicological responses. This study aimed to examine chiral status of the drugs withdrawn from the market. Methods: We searched the literature regarding withdrawn drugs between 1950-2020 due to safety-related issues and identified 395 drugs. We examined their chirality and assigned into one of three categories: achiral compound, chiral mixture, and pure enantiomer. We compared their distribution at ATC-1 level, duration on the market, and adverse drug reactions leading to their withdrawal. Results: We identified that 52.4% (n=207) of withdrawn drugs were achiral, whereas 27.6% (n=109) were chiral mixtures and 20.0% (n=79) were pure enantiomers. The mean duration on the market was 24.6±27.5 years. The groups did not differ in terms of mean duration on the market. Chiral mixtures were significantly more withdrawn than were achirals in cardiovascular system drugs (17.4% vs. 7.7%, p=0.01). In musculoskeletal system drugs, pure enantiomers were significantly less withdrawn (2.5%) compared to achirals (12.6%, p=0.01) and chiral mixtures (11.9%, p=0.03). Hepatotoxicity was significantly less common in pure enantiomers (5.4%) compared to chiral mixtures (12.7%, p=0.04) and achirals (17.0%, p<0.01). Cardiovascular toxicity was significantly more common in chiral mixtures (14.5%) compared to that in achiral drugs (7.5%, p=0.02). Conclusion: Our study showed slightly higher representation of chiral mixtures among withdrawn drugs over pure enantiomers. The assessment of withdrawal reasons further indicates higher tendency of chiral mixtures towards hepatotoxicity and cardiovascular toxicity.

Purpose: Dissemination of generic drug (GD) use could provide significant savings on drug expenditures and contribute to the long-term sustainability of healthcare. We aimed to exhibit the nationwide trend of GD use in primary care and investigate potentially relevant drug and patient factors. Methods: We analyzed all electronic prescriptions registered to national Prescription Information System by primary care physicians in Turkey during 2013-2016. We determined GD share in quantity and cost for each year. We further analyzed GD use in terms of patients’ demographic characteristics, most commonly prescribed preparations, and frequent indications. Results: In the four-year period, we identified 518,335,821 prescriptions, where GDs constituted 54.0% (n=786,972,813) with a total cost share of 36.9-37.8%. GD use was highest in 2016 (54.4%) and lowest in 2014 (53.6%). In each year, GD prescribing was higher in women (53.7-54.7%) than men (53.4-54.1%, p<0.001). GD utilization decreased as the age group increased, which was 64.0-64.5% in <18-year-old group and 46.0-47.1% in ≥75-year-old group. Among the top ten encountered indications, highest and lowest GD prescribing was detected in acute tonsillitis (68.1%) and hypertension (33.9). Metformin had the highest percentage of GD prescribing (96.1-97.7%) whereas esomeprazole showed the lowest GD prescribing (4.5-14.8%) among the most frequently used preparations in primary care. Conclusions: This study shows a modest upward trend of GD utilization in primary care, though its share appears as lower than expected. GDs were less likely to be prescribed in older age groups and seem as more pronounced in acute conditions, particularly infectious diseases.