How we monitor the safety

A medicine is considered  safe if its expected benefits are greater than the potential risks of adverse reactions associated with its administration. All medicines can cause adverse reactions. However, it is important to note that the majority of patients take medicines without experiencing any serious adverse reactions.
Before a medicine is placed on the market (pre-marketing period), extensive research must be conducted, namely: pre-clinical trials in animals and clinical trials in humans. Clinical trial programs follow strict rules and are designed to demonstrate the positive benefit-risk balance of a medicine used in treatment for a specified indication and patient population.
The medicine shall be granted marketing authorization if its quality, efficacy and safety are proven, which includes that the positive benefit-risk balance has been demonstrated at the time of authorization (demonstrated therapeutic efficacy and risks, in the form of adverse reactions, may be considered acceptable at the time).

Clinical trials are conducted under specific conditions:

  • Subjects are homogeneously selected specifically for this study according to strict criteria (gender, age, ethnicity, smoking, generally not haveing associated diseases and do not use other medicines concomitantly, etc.),
  • The number of subjects and duration of the study are limited,
  • Subjects are continuously monitored during the study.

Common adverse reactions are known at the end of the clinical trial. After obtaining marketing authorization, the medicine is placed on the market and starts being used in routine clinical practice on a large number of patients. Still, the overall safety profile of the medicine is not yet known, i.e. the information is incomplete or not available at all about the rare adverse reactions and reactions after long-term exposure, interactions, resistance, potential for medical errors, unauthorized use of the medicine, abuse and misuse, and administration of the medicine in specific categories of patients (children, elderly, pregnant women, breastfeeding women, patients with associated diseases: liver, kidney or heart failure, etc).
For these reasons, knowledge about the safety profile of the medicine is limited and must be expanded. Therefore, it is vital to monitor the safety of all medicines from the moment they are placed on the market – this is known as pharmacovigilance.

Pharmacovigilance is the process of:

  • Monitoring the use of a medicine in day-to-day practice to identify previously unrecognized, unexpected adverse reactions or changes in the patterns (nature, severity, frequency) of adverse reactions,
  • Assessing the risks and benefits of medicines in order to determine what actions should be taken, if necessary, to improve the safe administration of a medicine,
  • Providing information to healthcare professionals and patients in order to achieve safe and effective use of medicines,
  • Monitoring the impact and results of the actions taken.

Information sources used for pharmacovigilance:

  • Spontaneous adverse drug reaction reporting by healthcare professionals and patients,
  • Clinical and epidemiological studies,
  • Medical literature,
  • Information from the pharmaceutical industry,
  • Information from other worldwide regulatory authorities,
  • Databases (mortality, morbidity, pregnant women, etc.).

Information from these sources is thoroughly reviewed and analyzed and may identify a new adverse reaction, that had not been known for a particular medicine, indicate that certain adverse reactions occur more commonly than shown in the previously conducted trials, or indicate that certain patient populations more commonly experience adverse reactions, then detect interactions, possible medication errors, misuse, abuse etc.

Regulatory actions for safety reasons:

When necessary, after the evaluation of the collected data and identification of new safety findings, ALIMS takes steps to ensure that the medicine is used in a manner that minimizes risks and maximizes  benefits. These actions usually include changes to safety information in the Summary of Product Characteristics and Patient Information Leaflet, as primary documents on the medicine, namely:

  • In terms of adding new important warnings and precautions, and adverse reactions,
  • New contraindications (e.g. do not give this medicine to pregnant women, children, or use it in certain medical conditions, etc.),
  • Reduction of the recommended dose,
  • Limitations in the administration of a medicine (as second-choice therapy, exclusion of a certain disease or group of patients in which a medicine is administered, definition of a more restrictive regime for the issuance of medicine, e.g. from over-the-counter to prescription only, etc.).

Other regulatory actions are also taken for risk management purposes, particularly in terms of risk minimization, and in rare cases, the decision can be made to terminate a marketing authorization, or to temporarily revoke a marketing authorization for safety reasons and to withdraw a medicine from the market, when it is demonstrated that the potential risk is greater than the expected benefit in normal therapeutic administration of a medicine.

Pharmacovigilance is defined as a set of activities relating to the collection, detection, assessment, understanding and prevention of adverse reactions to a medicine, and other medicine-related issues.

An adverse reaction is any harmful and unintended reaction to a medicine occurring during the administration of the normal dose of a medicine to human subjects (for treatment, disease prevention, diagnosis, rehabilitation, improvement or alternation of  physiological function), or during the administration of any dose of a medicine in a clinical trial.

An unexpected adverse reaction is a reaction to a medicine whose nature, severity or outcome is not described in the Summary of Product Characteristics, i.e. Investigator’s Brochure for investigational medicines in clinical trials.

An adverse event is an undesirable experience occurring during the administration of a medicine for which the causal relationship with the administration of the medicine does not have to be proven. An adverse event is any unintended and undesirable signal (e.g. abnormal laboratory findings),  symptom or  disease that is time-related to the administration of a medicine.

A serious adverse event is any undesirable reaction/event with the following results:

  • Death,
  • Immediate life-threatening situation,
  • Permanent or significant disability/incapacity,
  • Requires hospitalization or prolongation of existing hospitalization,
  • Is a congenial anomaly or birth defect,
  • Other medically significant condition.

Interaction is a change in the pharmacokinetic or pharmacodynamic properties of a medicine caused by  theconcurrent administration of another medicine, food, or any other substance.

Overdose is the administration of a medicine in a single or daily dose in an amount that exceeds the maximum recommended individual or daily dose according to the Summary of Product Characteristics and Patient Information Leaflet, including cumulative effects due to overdose.

Unauthorized administration of a medicine is the administration of a medicine with marketing authorization, that is administered in a therapeutic indication, dosage or manner not listed in the Summary of Product Characteristics, or not approved.

Abuse of a medicine is the permanent or occasional, intentional excessive use of a medicine followed by harmful physical or psychological  effects.

Medical error is any unintentional error in prescribing, issuing or administration of a medicine by a healthcare professional or patient.
Occupational exposure to a medicine is the work-related exposure of a person to a medicine.