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. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n=4) was significantly higher (P<0.001) than among the remaining reports (580 out of 1982; n=2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter. CONCLUSION: The study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education.

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. Data were analyzed in respect of total number, gender, age, type, seriousness, expectedness, outcome, system organ class, suspected drug and reporter. RESULTS: The findings showed that 15% of all reported ADRs were caused by drugs from the ATC group N. 60% of these were caused by drugs belonging to the ATC subgroups N05 (psycholeptics) and N06A (antidepressants). A significant increase in the percentage of serious ADRs in the examined groups of medicinal products was observed. Analysis of expectedness showed that the share of unexpected ADRs is very high. CONCLUSION: The distribution of reporters is not satisfactory. The Agency, as regulatory authority, cannot undertake certain measures to improve the safe use of medicinal products without having reports. Only reporting of ADRs can result in changes to benefit all patient populations. Our joint aim should be avoiding a great number of ADRs and maintaining overall safe use of medicinal products.

Analysis of spontaneous reporting of suspected adverse drug reactions for non-analgesic over-the-counter drugs from 2008 to 2017.

BACKGROUND: Adverse drug reaction (ADR) reporting practices by health care professionals remain poor. Over-the-counter (OTC) drugs are perceived as safe; however, they can also cause ADRs. The objective of this study was to analyze ADR reporting for OTC drugs in a 10-year period, in order to evaluate frequency of ADRs, population that ADRs most affect and reporters of ADRs of OTC drugs in Croatia. METHODS: Spontaneously reported ADRs of non-analgesic OTC drugs, collected from January 2008 to December 2017 were analyzed. Data was obtained from Agency for Medicinal Products and Medical Devices of Croatia (HALMED). RESULTS: There were 547 ADRs of OTC drugs reported in total and an increase in number of reports through the years was observed. Pharmacists reported 45.4% of all ADRs, and were most frequent reporters (p < 0.001). In 2017 majority of reports, 62 (49.2%), were obtained from consumers. ADRs were most frequently observed in patients aged 70 years and older (15% of ADRs). Five percent of all reports were accidental exposures among children. CONCLUSIONS: Pharmacists most frequently reported ADRs of OTC drugs and consumers' awareness of ADR reporting has risen. Other health care professionals (e.g., nurses and dentists) must be offered proper education in order to improve reporting practice of ADRs. Health care professionals should address concerns about OTC drug safety in elderly and children.

Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

OBJECTIVE: Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014. METHODS: HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type. RESULTS: In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics. CONCLUSION: Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects.

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 1th March 2005 to 31th December 2013. RESULTS: 9175 ADR reports were reported in the Lombardy, 2457 were included in the Croatian database. The age groups most involved were 2-11 for both countries. The 13.2% and 40.3% of reports retrieved in Lombardy and Croatia were classified as serious, respectively. Fatalities account for 0.09% and 0.12% in Lombardy and Croatia, respectively. CONCLUSION: Data on serious reports reflect a similar scenario in terms of age range; strikingly different therapeutic subgroups were involved in reporting activity likely due to greater self-medication practices with penicillins and anti-inflammatory, analgesic and antipyretics drugs in Lombardy than in Croatia, highlighting the need to closely monitor this paediatric therapeutic area to ensure a safe use of these drugs.

National consumption of opioid and nonopioid analgesics in Croatia: 2007-2013.

BACKGROUND: The increased consumption of analgesics has been documented worldwide during the last 2 decades. The aim of the study was to examine the trends in opioid and nonopioid analgesic consumption in Croatia between 2007 and 2013. METHODS: Data on opioid consumption were extracted from the database of the national authority. All opioid and nonopioid analgesics were included in the analysis. Data were presented as defined daily doses per 1,000 inhabitants per day. Adequacy of opioid consumption was calculated using adequacy of consumption measure. RESULTS: During the examined 7-year period, the total consumption and total cost of all analgesics in Croatia showed continuous increase. In the M01A group (anti-inflammatory and antirheumatic products, nonsteroids), ibuprofen had an exponential increasing trend, and in 2011, it overtook diclofenac consumption. Ibuprofen and diclofenac had the highest consumption also in the M02A group of topical products for joint and muscular pain. Tramadol was by far the most consumed type of opioids (N02A group) and paracetamol in the group of other analgesics and antipyretics (N02B). The adequacy of consumption measure value was 0.19, indicating that Croatia is a country with a low opioid consumption. CONCLUSION: Between 2007 and 2013, both consumption of analgesics and their cost in Croatia had an increasing trend. Comparisons with data from other countries, based on the published literature, indicate that analgesic consumption in Croatia is still relatively low. Calculation of the adequacy of opioid consumption indicated that Croatia is a country with low opioid consumption. Further studies are necessary for establishing whether current analgesic consumption in Croatia corresponds to patient needs.