Objectives The primary objective of this paper is to describe and discuss new safety and efficacy findings of non-prescription medicinal products authorised in Croatia, which have been granted through variations of marketing authorizations in the previous 6-year period (from 1 July 2013 till 30 June 2019). The paper also provides an overview of the conclusions of the public assessment reports and recommendations available on the website of the European Medicines Agency (EMA), the European Commission (EC) and the Coordination Group on Mutual Recognition and Decentralised Procedure (CMDh) regarding the safety and efficacy of active substances as a compound of non-prescription medicines in Croatia, published during the same period as a result of joint assessment procedures at European Union level. The secondary objective is to determine the impact and consequences of introducing a new pharmacovigilance legislation on the acquisition of new scientific information regarding postmarketing safety and efficacy of non-prescription medicinal products, as well as implementation of those into product information. Materials and methods For the purposes of this paper, the scientific literature, legal acts in the field of human medicines regulation and relevant scientific guidelines available on the websites of the competent regulatory authorities were used, as well as databases (databases of Agency for Medicinal Products and Medical Devices (HALMED), European Medicines Agency (EMA), European Commission (EC) and Coordination Group for Mutual Recognition and Decentralised Procedure, Human Medicinal Products (CMDh)). Data on safety and efficacy variations of marketing authorization for non-prescription medicines in Croatia that resulted in product information amendments and granted in the period from 1 July 2019 to 30 June 2019 were collected by accessing the HALMED’s and EMA’s databases. Quantitative and qualitative analysis of these data were conducted. The overview of safety and efficacy joint assessment procedures at European Union level that are completed during the same period for active substances contained in the authorised non-prescription medicines in Croatia and corresponding recommendations for product information, was carried out by accessing EMA’s, EC’s and CMDh’s databases. The analysis included referrals procedures, the evaluation of safety signals, the assessment of periodic safety update reports (PSUR), the assessment of paediatric studies submitted under Article 45 and 46 of the Regulation (EC) No 1901/2006 and the overview of herbal monographs published in European Union (HMPC). List of authorised non-prescription medicinal products and related active substances, available in HALMED’s databases, was used during data search. Information on approved safety and efficacy variations are presented separately for medicinal products with active substances of chemical and herbal origin. For the chemical medicines /pharmaceuticals, results were analysed with regard to authorisation procedure (centralised, national, decentralised and mutual recognition procedure). Completed joint safety and efficacy assessment procedures at European Union level are presented separately according to the type of procedure. Results In the period from 1st July 2013 till 30th June 2019, a total of 487 clinical variations were granted for 239 non-prescription medicinal products with active substances of chemical origin authorised via national, mutual recognition and decentralised procedure in Croatia. Most common were major variations type II (52.2%) and changes under the category C.I.4 (new clinical and pharmacovigilance data) (41.5%). The major clinical variations (type II) were approved for 41 active substances/combinations of active substances, with a complete update of safety and efficacy data in many cases. According to the affected section of summary of product characteristics, more than 50% of approved requests included changes of adverse effects, warnings and precautions (sections 4.8 and 4.4) and about 30% of approved requests covered dosage, interactions and overdose information (sections 4.2, 4.5 and 4.9). During the same period, a total of 30 clinical variations was granted for 7 non-prescription centralised authorised medicinal products in Croatia, among which the majority refered to minor changes type IB (63.3%) and those classified as C.I.z (including PRAC recommendations and outcomes of PSUSA procedures). Changes of safety and efficacy data (including major changes) were made for each of the 4 active substances affected by clinical variations. According to the affected section of summary of product characteristics, 36.7% of the approved variations were related to warnings and precautions (section 4.4), 23.3% to drug interactions (section 4.5), 20.0% to adverse reactions (section 4.8), 13.3% to pharmacokinetic properties (section 5.2) and 10.0% to pharmacodynamic properties (section 5.1). In the same period, a total of 28 clinical variations were granted for 23 non-prescription herbal medicines. Highest frequency was observed for minor type IB variations (46.4%) and those classified as C.I.z (89.3%). Out of these, only 9 had impact on the content of clinical data and were related to the harmonisation with adopted EU herbal monograph or with new clinical data. All clinical sections are covered by these clinical variations. The overview of safety and efficacy joint assessment procedures in the European Union completed during the same period and related recommendations for product information published on the EMA's and other competent authorities' websites were carried out. Results relevant to non-prescription medicines in Croatia are shown in the table below. The results confirm the significant impact of the introduction of new pharmacovigilance legislation on the rapid acquisition of new information on safety and efficacy of non-prescription medicinal products and its greater scope. Direct consequence represent the higher number of granted safety and efficacy variations of marketing authorizations for this group of medicines and the larger number of requests for their implementation into the package leaflet. Conclusions For the correct use of non-prescription medicinal products, it is essential that patients /users read carefully the attached package leaflet before use, and (that) the pharmacists provide expert advice in accordance with valid product information issued by the competent authority. Given that more strict regulatory requirements for drug monitoring resulting in increased dynamics of new information on the safety and efficacy of non-prescription medicinal products, pharmacists and all healthcare professionals who have an advisory role in selection and use of medicinal products intended for self-medication, are obligated to educate themselves continuously and keep up with the amendments of these products information. The usage of the HALMED’s Medicinal Products Database in daily pharmacy practice raises the quality of pharmacy service and contributes to the safe and effective use of medicinal products not subjected to medical prescription. The cooperation between marketing authorisation holders and the competent authorities is necessary in order to provide accurate instructions on non-prescription medicinal products use to the patients/users and to ensure the timely implementation of new safety and efficacy findings into the package leaflet attached to packaging.