How we Monitor the Safety of Medicinal Products

Data gathered during the pre-authorisation phase of medicinal product development (non-clinical and clinical studies) can not identify all adverse reactions that may appear when the medicinal product has been marketed, due to the following reasons:

Investigations on animal models can not entirely foresee the safety of medicinal product use in humans
The duration of clinical trials and the number of subjects are limited, the conditions for use are different from those in clinical practice (i.e. defined diet, defined physical activity, subjects are not taking other medications simultaneously, do not have other diseases)
Information from clinical trials about rare and very rare adverse reactions, long term use, use in special groups of patients (e.g. children, elderly people, pregnant women, patients with severe impairment of kidney and/or liver function) or about medicinal product interactions are either incomplete or not available whatsoever

Pharmacovigilance is a process that includes:

Monitoring the safety of medicinal products use in every day clinical practice in order to identify previously unrecognised adverse reactions
Medicinal product benefit/risk assessment based on all available data, especially data from the post-marketing phase (after the medicinal product has been placed on the market)
Providing information to healthcare professionals and patients on safe and effective use of medicinal products
Monitoring the impact of undertaken risk minimisation measures

Information sources for effective pharmacovigilance:

Spontaneous reports of suspected adverse reactions
Data from clinical and epidemiological studies
Scientific literature
Information from marketing authorisation holders
Information from other regulatory authorities in EU and the world
Registries (mortality, morbidity, pregnant women etc.)

Data gathered from aforementioned sources is reviewed and analyzed in detail. Analysis of the data can identify new adverse reactions that were not previously known for a particular medicinal product, including side adverse reactions that appear after long-term use or adverse reactions that develop with delay (usually occurring after treatment has stopped). The analysis can also show that some of the adverse reactions appear more often than previous studies have shown, that some people or patient groups develop adverse reactions more often than others, etc.

These data may identify adverse reactions that are new and previously unknown, some of the adverse reactions may appear more often than revealed in clinical trials, some people or patient groups develop adverse reactions more often than others, some adverse reactions may appear after long term use or with a delay etc.

The data may lead to changes such as:

Restrictions in use of a medicinal product
Changes in posology of a medicinal product
Changes in the summary of product characteristics and package leaflet in indication parts, posology, contraindications, adverse reactions, warnings and precautions
Other regulatory actions

Spontaneous adverse reaction reporting

Healthcare professionals

The healthcare professional that comes in contact with a medicinal product or medicinal product user is required to report in written form every suspected adverse reaction to medicinal products marketed in Croatia (Art. 145 of the Medicinal Product Act, National Gazette No. 76/13) to the Agency, while suspected adverse reaction to vaccines marketed in the Republic of Croatia must be reported in written form to the Agency and the Croatian Institute for Public Health (hereinafter: HZJZ).

If the healthcare professional, due to objective reasons, is not able to report the suspected adverse reaction to both the Agency and the HZJZ, his obligation will be considered fulfilled after reporting to one of those institutions according to Art. 145 of the Medicinal Product Act (Art. 11 of the Ordinance on Pharmacovigilance, Official Gazette No. 83/13, 145/21).

Information about the identity of the person reporting the adverse reaction is confidential. When reporting an adverse reaction directly to the Agency, the Agency may not pass on information about the identity of the person reporting the adverse reaction to third parties, except in exceptional circumstances, with the written consent of the applicant. Individual adverse reaction, adverse event, medication error, overdosing, dependence or abuse reporting is considered confidential and scientific and may not be used in the process of responsibility judgment of the healthcare professional that prescribes or dispenses the medicinal product (Art. 14 of the Ordinance on Pharmacovigilance, Official Gazette No. 83/13, 145/21).

Patients

Patients should inform their doctor or pharmacist about any adverse reaction they have noticed or experienced, even ones not listed in the package leaflet.

Patients may personaly report any adverse reaction that they notice to the Agency via on-line forms (see also Adverse Reaction Reporting). Patients also contribute to the safety of medicinal products use by reporting adverse reactions.

Useful web pages where additional information is available about adverse reactions and pharmacovigilance: