Jong, G.W. 't

Effects of safety warnings on prescription rates of cough and cold medicines in children below 2 years of age (Article)

2011-06-01T00:00:00Z

AIM: The aim of the study was to assess the influence of national and international warnings on the prescription rates of cough and cold medicines (CCMs) in the youngest children (<2 years) in the Netherlands and Italy. METHODS: Analysis of outpatient electronic medical records of children <2 years in Italy and the Netherlands was carried out. Age and country specific prescription prevalence rates were calculated for the period 2005-08. Comparisons of prescription rates in 2005 (pre) and 2008 (post) warnings were done by means of a chi-square test. RESULTS: The cohort consisted of 99176 children <2 years of age. After international warnings, overall prescription rates for CCMs decreased slightly from 83 to 77/1000 person years (P= 0.05) in Italy and increased in the Netherlands from 74 to 92/1000 children per year. Despite the international warnings, prescription rates for nasal sympathomimetics and opium alkaloids increased in the Netherlands (P < 0.01). In Italy a significant decrease in the prescription rates of opium alkaloids and other cough suppressants (P < 0.01) was observed, and also a significant reduction in use of combinations of nasal sympathomimetics. CONCLUSION: Despite the international safety warnings and negative benefit-risk profiles, prescription rates of cough and cold medicines remain substantial and were hardly affected by the warnings, especially in the Netherlands where no warning was issued. The hazards of use of these medicines in young children should be explicitly stipulated by the European Medicines Agency and all national agencies, in order to increase awareness amongst physicians and caretakers and reduce heterogeneity across the EU. © 2011 The Authors. British Journal of Clinical Pharmacology

Risk of recurrent myocardial infarction with the concomitant use of clopidogrel and proton pump inhibitors (Article)

2011-01-01T00:00:00Z

Background: The association between myocardial infarction (MI) and co-administration of proton pump inhibitors (PPIs) and clopidogrel remains controversial. Aim: To quantify the association between concomitant use of PPIs and clopidogrel and occurrence of recurrent MI. Methods: We conducted a case-control study within a cohort of acute MI patients in PHARMO Record Linkage System (1999-2008). The cases were patients readmitted for MI. PPI exposure was categorized as current (3-1 days before MI), past (30-3 days before MI), or no use (>30 days before MI). We used conditional logistic regression analyses. Results: Among 23 655 patients hospitalized following MI, we identified 1247 patients readmitted for MI. Among clopidogrel users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.62, 95% CI: 1.15-2.27) when compared with no PPI use, but not when compared with past PPI use (OR: 0.95, 95% CI: 0.38-2.41). Among clopidogrel non-users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.38, 95% CI: 1.18-1.61) when compared with no PPI use. Conclusions The apparent association between recurrent MI and use of PPIs with clopidogrel depends on the design, and is affected by confounding by indication. The association is not present when (un)measured confounding is addressed by design.

Assessment of Pediatric asthma drug use in three European countries; A TEDDY study (Article)

2011-01-01T00:00:00Z

Asthma drugs are amongst the most frequently used drugs in childhood, but international comparisons on type and indication of use are lacking. The aim of this study was to describe asthma drug use in children with and without asthma in the Netherlands (NL), Italy (IT), and the United Kingdom (UK). We conducted a retrospective analysis of outpatient medical records of children 0-18 years from 1 January 2000 until 31 December 2005. For all children, prescription rates of asthma drugs were studied by country, age, asthma diagnosis, and off-label status. One-year prevalence rates were calculated per 100 children per patient-year (PY). The cohort consisted of 671,831 children of whom 49,442 had been diagnosed with asthma at any time during follow-up. 2-mimetics and inhaled steroids were the most frequently prescribed asthma drug classes in NL (4.9 and 4.1/100 PY), the UK (8.7 and 5.3/100 PY) and IT (7.2 and 16.2/100 PY), respectively. Xanthines, anticholinergics, leukotriene receptor antagonists, and anti-allergics were prescribed in less than one child per 100 per year. In patients without asthma, 2-mimetics were used most frequently. Country differences were highest for steroids, (Italy highest), and for 2-mimetics (the UK highest). Off-label use was low, and most pronounced for 2-mimetics in children <18 months (IT) and combined 2-mimetics + anticholinergics in children <6 years (NL). Conclusion: This study shows that among all asthma drugs, 2-mimetics and inhaled steroids are most often used, also in children without asthma, and with large variability between countries. Linking multi-country databases allows us to study country specific pediatric drug use in a systematic manner without being hampered by methodological differences. This study underlines the potency of healthcare databases in rapidly providing data on pediatric drug use and possibly safety.

Unlicensed and off-label prescription of respiratory drugs to children (Article)

2004-01-01T00:00:00Z

Many respiratory drugs are not available in formulations suitable for infants and toddlers. Efficacy and safety research is mostly restricted to older children. However, respiratory drugs are frequently used in children for common diseases like asthma, upper and lower respiratory tract infections, rhinitis and sinusitis. The unlicensed and off-label use of respiratory drugs in children were studied. A population-based cohort study was conducted by using the computerised medical records in the Integrated Primary Care Information project. The study population comprised a random sample from all children aged 0-16 yrs who were registered with a general practitioner in 1998. All prescriptions for respiratory drugs during the study period were classified according to their licensing and off-label status. The study population comprised 13,426 patients (51.7% male, median age 8.7 yrs), of whom 2,502 (19%) received 5,253 prescriptions for respiratory drugs in 1998. A total of 3,306 (62.9%) prescriptions concerned licensed drugs. Of the remaining 1,947 prescriptions (37.1%), 882 (16.8%) were unlicensed for use in children, and 1,065 (20.3%) were prescribed off-label. The 1-yr cumulative risk of receiving an unlicensed or off-label prescription was 45% among children with at least one prescription for a respiratory drug. This population-based study showed that a large proportion of respiratory drugs prescribed by the general practitioner are unlicensed for use in children, or licensed but prescribed in an off-label manner. Results have to be interpreted with caution because they may unjustly suggest inaccurate prescribing, whereas it may be difficult to treat children with respiratory symptoms and diseases, because for many respiratory drugs paediatric data on safety and efficacy are insufficient. These findings underline the importance of research on suitable formulations, dosages and efficacy of respiratory drugs in children.

Marketing in the lay media and prescriptions of terbinafine in primary care: Dutch cohort study (Article)

2004-01-01T00:00:00Z

Unlicensed and off-label drug use in children (Doctoral Thesis)

2002-04-10T00:00:00Z

Many commercially available drugs are only licensed for use in adults and for many drugs the available formulations are unsuitable for pediatric use.' This reality leads to use of drugs which are unlicensed or off -label for use in children. There are several reasons for this highly unsatisfactory situation. Firstly, children represent only a small market in an absolute sense but also relatively as most children are healthy. Hence, from a commercial perspective it may not be profitable to invest in pediatric drug research. Secondly, fear is growing for unforeseen adverse effects and long-term toxicity which may be difficult to study. Therefore, the current requirements for licensing of a drug may have become a barrier to make proper drugs available to a vulnerable group of patients. Thirdly, there are ethical problems to conduct drug studies in children. In Europe the problems in pediatric drug use and research receive relatively little interest and there is a substantial Jack of funding of pediatric drug research. N. a result, pediatric drug trials are relatively scarce and often include only a limited number of patients. Despite the well-known thalidomide disaster, which happened already forty years ago and caused an epidemic of congenital malformations, very little has changed regarding the labeling of drugs in infants and children. Although the disaster has stimulated legislation of drug licensing, children ironically remain 'therapeutic orphans'. This is difficult to accept because many diseases in adults can also occur in children while pharmacokinetics and pharmacodynamics often differ. Prescription of drugs should be proven to be equally safe in children as in adnlts, and efficacy of the product should be thoroughly assessed for all probable users. Exposure of infants and children to drugs which are not proven to be safe and efficacious during growth and development, cannot always be prevented. Hence, the health implications of this 'therapeutic orphanhood' may be larger than is sometimes assumed. The scope of this thesis was to assess the extent of the problem of unlicensed and offlabel drug use in children both in clinical care as well as in general practice. Although it is just a first step on a lengthy road, we hope that results of our studies may revive awareness of the problem and stimulate adequate regulatory actions.

Unlicensed and off label prescription of drugs to children: population based cohort study (Article)

2002-01-01T00:00:00Z

A survey of the use of off-label and unlicensed drugs in a Dutch children's hospital (Article)

2001-01-01T00:00:00Z

BACKGROUND: The treatment of pediatric patients with drugs in hospitals is being impeded by a shortage in the availability of licensed drugs in an appropriate formulation. We have studied the extent of use of drugs that are not licensed for use in children (unlicensed) and drugs that are used outside the terms of the product license (off-label). We conducted this study in a Dutch academic children's hospital. METHODS: In a prospective study of 5 weeks' duration, we reviewed drug prescriptions in a pediatric ward and 3 intensive care units. We classified the prescribed drugs in 3 main categories-licensed, unlicensed, and off-label-and determined the nature of their unlicensed and off-label use. RESULTS: Two thousand one hundred thirty-nine courses of drugs were administered to 237 patients in 442 patient-days. Of 2139 prescriptions, 725 (34%) were licensed, 1024 (48%) were unlicensed, and 390 (18%) were off-label. In 392 (90%) of 435 patient-days, children received 1 or more courses of an unlicensed or off-label drug prescription in hospital. CONCLUSION: With regard to the availability of drugs of proven quality and adequate license for pediatric patients in hospital, dramatic shortcomings exist. As a result, drug legislation originally designed to protect patients and prescribing physicians against unsafe drug use and unjustified claims has turned into an insurmountable threshold to make proper drugs available for a vulnerable minority of patients.