The STAR Compass to Guide Future Pharmacovigilance Based on a 10-Year Review of the Strengthened EU System.

This article reflects on the 2010 pharmacovigilance legislation of the European Union (EU). Its legislative aim of better patient and public health protection through new responsibilities for pharmaceutical companies and regulatory bodies is considered to have been achieved and is well supported by the good pharmacovigilance practices 'EU-GVP'. For future progress, we set out a vision for high-quality pharmacovigilance in a world of ongoing medical, technological and social changes.

Smart Safety Surveillance (3S): Multi-Country Experience of Implementing the 3S Concepts and Principles.

Introduction: The Smart Safety Surveillance (3S) concept is based on the understanding that, when faced with competing pharmacovigilance priorities, countries will have to invest judiciously, by focusing on new priority products, sharing work and resources with other countries when possible and building national competence for those activities that cannot be delegated.

Method: The 3S principles were applied to Armenia, Brazil, Ethiopia, India, Peru and Thailand using three priority products: bedaquiline, rotavirus vaccine and tafenoquine. A baseline assessment of pharmacovigilance preparedness was used to identify gaps and establish a work plan.

Enhancing Pharmacovigilance Capabilities in the EU Regulatory Network: The SCOPE Joint Action.

In November 2013, a team of European regulators initiated the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action. Funded by the Health Programme of the European Union, and with contributions from the involved Member States, SCOPE gathered information and expertise on how regulators in Member States run their national pharmacovigilance systems to meet the requirements of the pharmacovigilance legislation that came into effect in June 2012. The SCOPE project evaluated then-current practices and developed tools to further improve the skills and capability in the pharmacovigilance network.

Rosuvastatin-Induced Rhabdomyolysis - Possible Role of Ticagrelor and Patients' Pharmacogenetic Profile.

Up to the beginning of 2018, a total of eight cases describing rare but clinically important drug interactions between rosuvastatin and ticagrelor which resulted in rhabdomyolysis have been noted in the Global World Health Organization (WHO) adverse drug reaction (ADR) database (VigiBase) as well as in available literature. There are several possible factors which could contribute to the onset of rhabdomyolysis: old age, initially excessive rosuvastatin dose, drug-drug interactions (DDI) on metabolic enzymes (CYPs and UGTs) and drug transporter levels (ABCB1, ABCG2, OATP1B1) and pharmacogenetic predisposition. We reviewed all available cases plus the case of an 87-year-old female Croatian/Caucasian patient who developed rhabdomyolysis following concomitant treatment with rosuvastatin and ticagrelor.

A retrospective review of paediatric adverse drug reactions reported in Lombardy and Croatia from 2005 to 2013.

Objective: to characterise the adverse drugs reactions (ADRs) reported in the Lombard and Croatian paediatric population and to compare data to specific paediatric age groups, in terms of trend, pattern and severity of ADRs, increasing understanding of paediatric ADRs.

Research Design And Methods: We selected and analysed all the spontaneous reports in which children were involved (0 < 18 years old) reported in the Lombardy and in Croatian pharmacovigilance databases from 1 March 2005 to 31 December 2013.

Results: 9175 ADR reports were reported in the Lombardy, 2457 were included in the Croatian database.

Patient-Reported Safety Information: A Renaissance of Pharmacovigilance?

The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years have passed since the legislation was introduced and the key question is: does pharmacovigilance yet make optimal use of patient-reported safety information? Independent research has shown beyond doubt that patients make an important contribution to pharmacovigilance signal detection.

ABCG2 gene polymorphisms as risk factors for atorvastatin adverse reactions: a case-control study.

Aim: To explore the association between dose-related adverse drug reactions (ADRs) of atorvastatin and polymorphisms of ABCG2, taking into account the influence of CYP3A4 and SLCO1B1 genes.

Materials & Methods: Sixty patients who experienced atorvastatin dose-related ADRs and 90 matched patients without ADRs were enrolled in the study. Genotyping for ABCG2 421C > A, CYP3A4*22, SLCO1B1 388A > G, SLCO1B1 521T > C variants was performed by real-time PCR.

Clinical Application of Genotype-guided Dosing of Warfarin in Patients with Acute Stroke.

Background: Patients with certain types of stroke need urgent anticoagulation and it is extremely important for them to achieve fast and stable anticoagulant effect and receive individualized treatment during the initiation of warfarin therapy.

Methods: We conducted a prospective study among 210 acute stroke patients who had an indication for anticoagulation and compared the impact of CYP2C9 and VKORC1 genotype-guided warfarin dosing (PhG) with fixed dosing (NPhG) on anticoagulation control and clinical outcome between groups.

Results: PhG achieved target INR values earlier, i.

CYP2C9 and ABCG2 polymorphisms as risk factors for developing adverse drug reactions in renal transplant patients taking fluvastatin: a case-control study.

Aim: To investigate whether an association exists between fluvastatin-induced adverse drug reactions (ADRs) and polymorphisms in genes encoding the metabolizing enzyme CYP2C9 and the drug transporter ABCG2 in renal transplant recipients (RTRs).

Materials & Methods: Fifty-two RTRs that experienced fluvastatin ADRs and 52 controls matched for age, gender, dose of fluvastatin and immunosuppressive use were enrolled in the study. Genotyping for CYP2C9*2, *3 and ABCG2 421C>A variants was performed by real-time PCR.

Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study.

Aim: To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence.

Methods: In this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them.

Results: HALMED received 1209 reports involving at least two drugs.

Pain relief in medical patients: does clinical judgment and prescribing knowledge suffice?

The aim of this study was to evaluate the quality of pain management in hospitalised patients. A cross-sectional study design that included all medical patients experiencing pain was used. Out of 167 patients hospitalized at the Department of Medicine at the University Hospital Zagreb, 41 patients were experiencing pain and 40 out of them received analgesics.

[Adverse drug reactions of hydroxymethylglutaryl-CoA reductase inhibitors reported to agency for medicinal products and medical devices].

Hydroxymethylglutaryl-CoA reductase inhibitors (statins) are drugs used in the treatment of chronic diseases and frequently in concomitant therapy with many other drugs. Therefore, the risk of adverse drug reactions (ADRs), especially those caused by interactions is high. Aim of the study was to describe and analyze ADRs caused by statins reported to Croatian Agency from March 2005 to December 2008, and to emphasize reasons of their occurrence.

Adverse drug reactions of psycopharmacs.

Background: The objective of analysis of ADRs caused by drugs that pertain to the ATC group N (nervous system), as reported to the Croatian Agency for Medicinal Products and Medical Devices for the period from March 2005 to December 2008, was to examine the types of ADRs collected in said period, the profile of reporters and the possible impacts this could have on prescribing this group of medicinal products in the future.

Subjects And Methods: A retrospective observational study of ADRs was performed. Drugs causing ADRs were grouped according to the ATC drug classification, and subsequently entered into a database.

Regulating medicines in Croatia: five-year experience of Agency for Medicinal Products and Medical Devices.

Aim: To present the activities of the Agency for Medicinal Products and Medical Devices in the first 5 years of its existence and to define its future challenges.

Methods: Main activities within the scope of the Agency as a regulatory authority were retrospectively analyzed for the period from 2004-2008. Data were collected from the Agency's database and analyzed by descriptive statistics.

Vaccine regulations in Croatia.

In this paper legal prerequisites for vaccine licensure in Croatia are discussed. The Croatian legislation concerning vaccine licensing, marketing authorisation and utilization is reviewed. The procedures for including a vaccine into the Mandatory Childhood Vaccination Programme are also discussed with focus on Human papillomavirus (HPV) vaccines.

Use of gastroprotective agents in recommended doses in hospitalized patients receiving NSAIDs: a drug utilization study.

Objective: In recent years, studies investigated to what extend recommendations for co-prescribing gastroprotective agents in prevention of NSAID-induced gastrointestinal complications are followed in clinical practice. However, only a few studies have also taken into consideration the recommended dose of gastroprotectives prescribed in NSAID-induced ulcer prophylaxis. The aim of our study was to evaluate the prevalence of concomitant use of gastroprotectives with NSAIDs in hospitalized patients, with emphasis on the recommended dose of gastroprotectives for ulcer prophylaxis.

[Evaluation of justification for antibiotic use at the Internal Medicine Clinic of the Clinical Hospital in Zagreb].

Objective: Resistance to antimicrobials as the result of unnecessary and inadequate use of antibiotics has become a global health problem. It is estimated that up to 50% of antimicrobials are used unnecessarily, and that they are the cause of approximately 25% of adverse drug reactions. Efforts are made to ensure a controlled use of antibiotics, which is the key strategy against development of resistance to antimicrobials.

Acquired coagulopathy due to anticoagulant rodenticide poisoning.

A 35-year-old woman was admitted to hospital because of epistaxis, hematomas, and metrorrhagia. Laboratory data indicated severe coagulopathy with prolonged prothrombin time and decreased serum concentrations of vitamin K-dependent clotting factors II, VII, IX, and X. The patient denied taking any oral anticoagulants.