Medicines for an aging population: The EMA perspective and policies.

The European Medicines Agency adopted their Geriatric Medicines Strategy more than a decade ago. The strategy aims at elucidating the evidence basis for marketing authorization of new medicines which will be used in the older population, and at ensuring the appropriate communication of findings to the patient and healthcare provider. During the past decade new tools and data sources have emerged to support the strategy goals, and their use should be considered.

Inclusion of functional measures and frailty in the development and evaluation of medicines for older adults.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E7, the guidance for the conduct of clinical trials in people older than age 65 years, dates from 1994. Since then, the inclusion of older people in clinical trials has hardly improved, particularly for the oldest old age group (individuals older than age 75 years), which is the fastest growing demographic bracket in the EU. Even though most medications are taken by this group, relevant endpoints and safety outcomes for this cohort are rarely included and reported, both in clinical trials and regulatory approval documents.

Root cause analysis of medication errors of the most frequently involved active substances in paediatric patients.

Background: Use of medicinal products in paediatric patients is identified as a risk factor for the occurrence of medication errors.

Objectives: To describe and identify root causes of medication errors in children and adolescents spontaneously reported to Agency for Medicinal Products and Medical Devices of Croatia (Agency).

Method: Agency's adverse drug reaction database was searched by using the Standardised MedDRA Query: medication errors (Broad) with data lock point set at 30th June 2022.

The readiness of the spontaneous reporting system for COVID-19 vaccines safety monitoring in Croatia.

We aimed to identify whether a spontaneous reporting system (SRS) in Croatia could timely identify and confirm signals for COVID-19 vaccines. Post-marketing spontaneous reports of adverse drug reactions (ADRs) following COVID-19 immunisation reported to the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) were extracted and analysed. 6624 cases reporting 30 655 ADRs following COVID-19 immunisation were received from 27 December 2020 to 31st December 2021.

Cohort Event Monitoring of Adverse Reactions to COVID-19 Vaccines in Seven European Countries: Pooled Results on First Dose.

Introduction: COVID-19 vaccines were rapidly authorised, thus requiring intense post-marketing re-evaluation of their benefit-risk profile. A multi-national European collaboration was established with the aim to prospectively monitor safety of the COVID-19 vaccines through web-based survey of vaccinees.

Methods: A prospective cohort event monitoring study was conducted with primary consented data collection in seven European countries.

Use of pharmacogenomics in elderly patients treated for cardiovascular diseases.

Older people are increasingly susceptible to adverse drug reactions (ADRs) or therapeutic failure. This could be mediated by considerable polypharmacy, which increases the possibility of drug-drug and drug-gene interactions. Precision medicine, based on individual genetic variations, enables the screening of patients at risk for ADRs and the implementation of personalized treatment regimens.

Implementation of pharmacogenomics in product information.

The aim of our study was to analyse the level of implementation of pharmacogenomics (PGx) in product information (PI) of medicinal products approved through national procedures in the EU. In the analysis, we included nationally approved medicinal products in Croatia if guidelines for relevant substances were published. Overall, 265 marketing authorizations were analyzed.

Adverse drug reactions that arise from the use of medicinal products outside the terms of the marketing authorisation.

Background: New European (EU) pharmacovigilance (PV) legislation, introduced in 2012, widened the scope of an Adverse Drug Reactions (ADR) definition so that it also includes noxious and unintended response to a medicinal product arising from the use outside the terms of the marketing authorisation (MA), whereby the use outside the MA also includes off-label use, overdose, misuse, abuse and medication errors (MEs).

Objectives: To explore the ADRs arising from the use outside the terms of the MA reports in the Croatian pharmacovigilance database.

Methods: A retrospective, observational study of the HALMED PV database was undertaken before and after the implementation of the new legislation in Croatia.

Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Croatian population.

Background: Data on the frequency of pharmacogenetic polymorphisms in the Croatian population are limited. We determined and analyzed frequencies for the most important CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 genetic variants in the Croatian population.

Methods: 2637 subjects were included.

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.

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.

[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.