A.C.G. Egberts

Characteristics of Topics in Pharmacovigilance in The Netherlands

SummaryA retrospective analysis was made of the nature and composition of 107 consecutive topics presented in publications by or in collaboration with the national pharmacovigilance centre in The Netherlands, containing data obtained through ‘spontaneous reporting’. These topics were published in various national and international professional journals or special bulletins or as ‘dear doctor letters’. The topics constituted a wide variety of events and disorders. There was, however, a predominance of concrete, characteristic and often serious diseases, notably specific hypersensitivity reactions (43%, e.g. anaphylaxis, blood dyscrasias and liver injury), toxic manifestations or syndromes (30%, especially involving the nervous system), and drug interactions (13%). Most topics presented predominantly qualitative information. 62% of topics concerned type B, 33% type A and 3% type C adverse drug effects. The topics often referred to small numbers of case reports: 10 or less in 70% of the 107 topics. 46% of the topics concerned new information. There was some predominance of established (56%) over new drugs. Five pharmacotherapeutic groups accounted for 74% of topics. Of the 72 approved drugs or drug groups, 12 (17%) have been removed from the market. These findings increase our understanding of the functioning of pharmacovigilance and may enable further improvement of the methods and strategies involved.

The relation between the blood benzodiazepine concentration and performance in suspected impaired drivers

Several experimental studies have shown a negative influence of benzodiazepines on driving skills. The objective of this study is to study the relationship between the blood concentration of benzodiazepines and the influence on performance in field sobriety tests. A retrospective case file evaluation was conducted to select cases of drivers, tested positive for benzodiazepines only in the period from January 1999 to December 2004. Drivers were grouped into the categories sub therapeutic, therapeutic or elevated concentrations. The outcome of the tests (walking, walking after turn, nystagmus, Rombergs test, behavior, pupils and orientation) was binomial. A Chi square test was used to assess differences in proportions of the categorized cases. In total 171 cases were included. Observations of behavior (n=137; p<0.01), walking (n=109; p<0.01), walking after turn (n=89; p=0.02) and Rombergs test (n=88; p<0.05) were significantly related to the benzodiazepine concentration. There was no significant relation between benzodiazepine concentration and effect on pupil size, nystagmus or orientation. The results of our study indicate a relation between the concentration of benzodiazepines and the results of some performance tests. More effort is needed to standardize the tests and to determine the sensitivity and selectivity of the tests for benzodiazepines.

Patients' concerns about and problems experienced with discontinuation of antidepressants

Objective Clinical trials and epidemiological studies have shown that premature discontinuation is a major problem during antidepressant therapy. Unfortunately, there is little information on how patients perceive treatment with antidepressants in clinical practice, and it is unclear whether patients perceive discontinuation as a problem. The objective of this study is to assess whether concerns and problems experienced with drug discontinuation occur more frequently in patients using antidepressants than in patients using benzodiazepines, antipsychotics or non‐psychiatric medication.

Actual versus recommended storage temperatures of oral anticancer medicines at patients’ homes

Background Substantial quantities of unused medicines are returned by patients to the pharmacy each year. Redispensing these medicines would reduce medicinal waste and health care costs. However, it is not known if medicines are stored by patients as recommended in the product label. Inadequate storage may negatively affect the medicine and reduce clinical efficacy whilst increasing the risk for side effects. Objective To investigate the proportion of patients storing oral anticancer medicines according to the temperature instructions in the product label. Methods Consenting adult patients from six Dutch outpatient hospital pharmacies were included in this study if they used an oral anticancer medicine during February 2014 – January 2015. Home storage temperatures were assessed by inclusion of a temperature logger in the original cancer medicines packaging. The primary outcome was the proportion of patients storing oral anticancer medicines as specified in the Summary of Product Characteristics, either by recalculating the observed temperature fluctuations to a single mean kinetic temperature or by following the temperature instructions taking into account a consecutive 24-h tolerance period. Results Ninety (81.1%) of the 111 included patients (47.8% female, mean age 65.2 (SD: 11.1)) returned their temperature loggers to the pharmacy. None of the patients stored oral anticancer medicines at a mean kinetic temperature above 25℃, one patient stored a medicine requiring storage below 25℃ longer than 24 h above 25℃. None of the patients using medicines requiring storage below 30℃ kept their medicine above 30℃ for a consecutive period of 24 h or longer. Conclusion The majority of patients using oral anticancer medicines store their medicines according to the temperature requirements on the product label claim. Based on our results, most oral anticancer medicines will not be negatively affected by temperature conditions at patients’ homes for a maximum of three months and are likely to be suitable for redispensing.

Comparison of antibiotic dosing recommendations for neonatal sepsis from established reference sources

Background Incorrect dosing is the most frequent prescribing error in neonatology, with antibiotics being the most frequently prescribed medicines. Computer physician order entry and clinical decision support systems can create consistency contributing to a reduction of medication errors. Although evidence-based dosing recommendations should be included in such systems, the evidence is not always available and subsequently, dosing recommendations mentioned in guidelines and textbooks are often based on expert opinion. Objective To compare dosage recommendations for antibiotics in neonates with sepsis provided by eight commonly used and well-established international reference sources. Setting An expert team from our Dutch tertiary care neonatal intensive care unit selected eight well-established international reference sources. Method Daily doses of the seven most frequently used antibiotics in the treatment of neonatal sepsis, classified by categories for birth weight and gestational age, were identified from eight well-respected reference sources in neonatology/pediatric infectious diseases. Main outcome measure Standardized average daily dosage. Results A substantial variation in dosage recommendations of antibiotics for neonatal sepsis between the reference sources was shown. Dosage recommendations of ampicillin, ceftazidime, meropenem and vancomycin varied more than recommendations for benzylpenicillin, cefotaxime and gentamicin. One reference source showed a larger variation in dosage recommendations in comparison to the average recommended daily dosage, compared to the other reference sources. Conclusion Antibiotic dosage recommendations for neonates with sepsis can be derived from important reference sources and guidelines. Further exploration to overcome variation in dosage recommendations is necessary to obtain standardized dosage regimens.

O2.21: Practical problems with medication use experienced by older people: a qualitative study

1 Dept of Public Health Effects, National Institute for Public Health and the Environment (RIVM), Bilthoven; 2 Dept of Geriatric Medicine&Expertise Centre Pharmacotherapy in Old Persons, UMC Utrecht; 3 Dutch Medicines Evaluation Board, Utrecht; 4 Dept of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharma ceutical Sciences (UIPS), Utrecht University, Utrecht; 5 Dept of Clinical Pharmacy, UMC Utrecht