How do we Monitor Safety of Medicinal Products?

Data gathered during the pre-authorisation phase of medicinal product development (non-clinical and clinical studies) can not predict all adverse reactions that may appear when the medicinal product has been marketed.

Reasons are following:

  • Investigations on animal models can not entirely foresee the safety of medicinal product use in humans.
  • Subjects taking part in in clinical trials are selected, 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), the duration and the number of subjects is limited.
  • By the time of placing the product on the market, due to a limited number of patients taking the medicinal product during the clinical trial, only adverse reaction that appear more often may be discovered.
  • Information about rare adverse reactions, toxic effects, long term use, use in special groups of patients (like children, elderly people, patients with renal or hepatic diseases) or about medicines interactions are either incomplete or not available whatsoever.

Pharmacovigilance is a process of:

  • Monitoring adverse reactions to medicinal products in every day's practice with a view to identify previously not recognised adverse reactions
  • Medicinal product benefit/risk assessment
  • Providing information to healthcare professionals and patients about a safe and effective use
  • Monitoring of impact of undertaken measures and procedures

Information sources for an effective pharmacovigilance:

  • Spontaneous reporting
  • Clinical and epidemiological studies
  • Medical literature Information from pharmaceutical industry
  • Information from other regulatory authorities in the world
  • Registries (mortality, morbidity, pregnant women etc.)

Information gathered from the aforementioned sources are selected and analysed in details. 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.

These data may lead to changes such as:

  • Restrictions in use of medicinal product
  • Changes in posology of 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).

The healthcare professional that comes in contact with the user of vaccine is required to report in written form to the Agency and the Croatian Institute for Public Health (hereinafter: HZJZ) every suspected adverse reaction to the vaccines marketed in the Republic of Croatia. If the healthcare professional from objective reasons is not able to report the adverse reaction to both the Agency and the HZJZ, his obligation will be considered fulfilled after reporting to one of those institutions (Art. 11 of the Ordinance on Pharmacovigilance, Official Gazette No. 83/13).

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).

(see also Adverse Reaction Reporting)


In order to successfully continue the treatment, Patients should consult with their doctor or pharmacist about the adverse reaction they have discovered.

Adverse reactions that they discover, patients may personaly report to the Agency via forms (see also Adverse Reaction Reporting).

Useful web pages where you may find additional information about adverse reactions and pharmacovigilance: