8 research outputs found
Drug treatment in children with focus on off-label drug use
ABSTRACT
There is a lack of paediatric documentation concerning efficacy and
safety of many
drugs, which contribute to drug use outside the terms of the product
license (off-label).
In the present thesis, four studies (I-IV), using different settings and
design to evaluate
pharmacological treatment in children, with focus on off-label drug use,
is presented.
Outpatient records of purchased prescriptions were retrieved to
investigate the
frequency and characteristics of paediatric off-label prescribing (I). In
Stockholm, 1.8
prescribed drugs per child were purchased in the year 2000. Every fifth
drug was
classified as an off-label prescription. The proportion of off-label
prescriptions was
highest for topical drugs, due to lack of paediatric information.
A survey of all adverse drug reaction reports to the Medical Products
Agency
concerning paediatric outpatients in the year 2000 was performed, to
investigate the
frequency of off-label drug prescribing (II). One hundred and twelve
paediatric cases,
corresponding to 158 adverse reactions were reported. One third of the
reports were
regarded as serious, and these were more often associated with off-label
drug
prescribing. Antiasthmatic drugs were most commonly reported. Psychiatric
symptoms
were the most commonly reported adverse drug reactions.
Paediatric questions and answers to a Drug Information Centre in
Stockholm were
retrieved and analysed regarding off-label drug use and paediatric
literature information
adding to the labelling of the drug (III). During a 10-year period, 249
paediatric
questions were handled. Every third question concerned off-label
treatment, often
concerning psychotropic drugs. In every other response to off-label
questions,
additional paediatric documentation concerning the drug was found in the
literature.
In a prospective, nation-wide, cross-sectional study, paediatric
prescriptions and offlabel
drug use to children at hospitals in Sweden were analysed (IV). Enrolment
of
more than 200 hospital departments resulted in data from 2947 paediatric
patients, that
received altogether11294 prescriptions within two two-day-periods in
2008. Half of all
administered prescriptions concerned either off-label drug use or
unlicensed or
extemporaneously prepared drugs. Paracetamol was the most common drug
used both
on- and off-label. Absence of paediatric information was the main reason
for the large
proportion of off-label prescribing of carbohydrates and electrolytes in
hospitals.
This thesis has demonstrated substantial off-label prescribing to
children in both
primary and hospital health care. A common reason for this is the lack of
paediatric
documentation. Children have the same right as adults to well documented
and safe
drug therapy. Therefore, it is necessary to improve paediatric
documentation through
harmonization of existing scientific knowledge and clinical experience,
improved
structure of SPC information, and more appropriate administration forms.
Furthermore, the documentation of drug treatment and its outcomes,
including the
reporting of adverse drug reactions, need to be improved
Does the EU's Paediatric Regulation work for new medicines for children in Denmark, Finland, Norway and Sweden? : A cross-sectional study
Objective The aim of this study was to assess the marketing status of the new paediatric medicinal products listed in the 10-year report as initially authorised between 2007 and 2016, reflecting the product availability in four Nordic countries. Design This is a cross-sectional study. Setting Analysis of the national medicine agency's databases in Denmark, Finland, Norway and Sweden. Data source New medicinal products with paediatric indications and new paediatric formulations listed in the Annex of European Medicines Agency's EU Paediatric Regulation 10-year report. Data analysis The products were classified according to national marketing status between January 2019 and March 2019, whether a product was authorised and whether the product was marketed. Main outcome measures The percentages of the new medicinal products with paediatric indications and new paediatric formulations having a valid marketing authorisation and being marketed, both in terms of the sums of all countries and separately for each country. Results Across the four countries, 21%-32% (16/76-24/76) of the new medicinal products were not marketed. Of the new formulations relevant to children, 29%-50% (16/56-28/56) were not marketed, and a significant proportion of these products had never been marketed. Conclusions This study reflects the reality of the implementation of the Paediatric Regulation. The results show that several new paediatric medicines and new formulations are not marketed. This affects the product availability. Similar data from other countries are needed to evaluate the overall European status to find remedies to current situation and increase the availability of the medicines for children. ©Peer reviewe
Off-label drug treatment and related problems in children : A register based investigation
Introduction: There is a lack of pediatric documentation concerning
efficacy and safety of many drugs, which may contribute to off-label drug
treatment and increase the risk for adverse drug reactions (ADRs).
Aims: To; (I) analyse the frequency and characteristics of pediatric
off-label prescribing; (II) investigate frequency of off-label drug
prescribing in pediatric ADR reports; (III) analyse drug related
problems, the extent of off-label drug treatment in pediatric questions
to a Drug Information Centre (DIC) and pediatric literature information
adding to the labelling of the drug in DIC answers.
Methods: Three retrospective register based investigations on drug
treatment of children less than 16 years of age were performed. In study
I, outpatient records of purchased prescriptions were retrieved and
analysed. The analysis was restricted to the drugs that account for 90%
of the total use (DU90%). In study II, a nation-wide survey of ADR
reports to the Medical Products Agency in relation to prescriptions among
suspected drugs in outpatients was performed. In study III, questions and
answers (Q&A) to a DIC in Stockholm (1995-2004) were characterised and
analysed.
Results: In Stockholm 1.8 prescribed drugs per pediatric outpatient were
purchased in the year 2000. Every fifth drug was classified as an
off-label prescription. The proportion of off-label prescription was
highest for topical drugs, followed by psychotropic drugs. In the year
2000, 112 pediatric ADR reports corresponding to 158 ADRs in outpatients
were reported. The off-label proportion in ADR reports was more than 40%.
One third of the reports was regarded as serious and these were more
often associated with off-label drug prescribing. Antiasthmatic drugs
were most commonly reported. Psychiatric symptoms were the most commonly
reported ADRs. During a 10-year period DIC in Stockholm handled 249
pediatric questions and each question addressed on average 1.5 drugs. The
questions mainly concerned drugs licensed in Sweden. Adverse drug
reactions (ADRs), drug choice or dosing were the most common drug related
problems. Every third question was off-label and among these the most
common therapeutic group was psychotropic drugs. In every other response
to offlabel questions, pediatric documentation concerning drug efficacy
and safety was found. The most common reason for a drug to be classified
as off-label was lack of pediatric labelling in the Swedish catalogue of
medical products.
Conclusion: This thesis has demonstrated substantial off-label
prescribing in primary health care. Off-label prescribing were common in
pediatric ADR reports from primary care. We also found literature
information adding to the labelling of the drug. There is a great need
for evidence based pediatric drug information, which can be retrieved
from a DIC. A future challenge is to further diffuse this knowledge to
pediatric prescribers through Internet, expert committees and medical
journal databases
Melatonin Prescription in Children and Adolescents in Relation to Body Weight and Age
The prescription of melatonin to children and adolescents has increased dramatically in Sweden and internationally during the last ten years. In the present study we aimed to evaluate the prescribed melatonin dose in relation to body weight and age in children. The population-based BMI Epidemiology Study Gothenburg cohort has weight available from school health care records, and information on melatonin prescription through linkage with high-quality national registers. We included prescriptions of melatonin to individuals below 18 years of age where a weight measurement not earlier than three months before, or later than six months after the dispensing date, was available (n = 1554). Similar maximum doses were prescribed to individuals with overweight orobesity as to individuals with normal weight, and to individuals below and above 9 years of age. Age and weight only explained a marginal part of the variance in maximum dose, but were inversely associated and explained a substantial part of the variance in maximum dose per kg. As a result, individuals overweight or with obesity, or age above 9 years, received lower maximum dose per kg of body weight, compared with individuals with normal weight or below 9 years of age. Thus, the prescribed melatonin dose to individuals under 18 years of age is not primarily informed by body weight or age, resulting in substantial differences in prescribed dose per kg of body weight across BMI and age distribution
Prevalence of potential drug-drug interactions in Swedish pediatric outpatients.
PurposeTo describe the occurrence of potential drug-drug interactions (DDIs) in prescribed drugs, dispensed to pediatric outpatients in Sweden.MethodsA cross sectional study was conducted based on data from a national register of prescribed drugs, dispensed at pharmacies, to children 0-17 years old. The study period was January 1 to April 30, 2010. Drug dispensing data was linked to the DDI database SFINX. Prevalence and frequencies of potential interactions were investigated, and drugs commonly involved in interactions were identified. The study focused on clinically relevant potential interactions, class D (should be avoided), and class C (can be handled, e.g. by dose adjustment).ResultsIn the Swedish pediatric population, 0 to 17 years of age, 12% (n = 231 078) of children had at least two dispensed drugs. In this group of patients, 0.14% had potential D-interactions and 1,3% had potential C-interactions. The number of D- and C-interactions that may lead to reduced effects were 181 (52%), and 1224 (32%) respectively. The ten most frequent drugs were involved in 78% and 65% of all potential D-, and C-interactions respectively. Furthermore, 80%, and 58% of the D-, and C-interactions respectively occurred in patients aged 12 to 17.ConclusionsWe identified a limited number of drugs that were represented in the majority of potential interactions. Interactions that can lead to a reduced treatment effect constituted approximately half of D-interactions, and a third of C-interactions. The frequency of potential interactions was higher in older children. The results may contribute to increased prescriber awareness of important potential drug interactions among pediatric outpatients
Evidence-based Anti-seizure Monotherapy in Newly Diagnosed Epilepsy: a New Approach
ObjectivesTo describe the process and results of the updated Swedish practice guidelines for monotherapy in epilepsy.Materials and MethodsThe Swedish Medical Products Agency led the process together with medical experts. Evidence rating in accordance with the International League Against Epilepsy (ILAE) template was linked to the Cochrane group's GRADE system. Evidence from recently published trials and metaâanalyses was added. A national expert panel participated in the project and contributed their clinical experience.ResultsIn seizures with focal onset, carbamazepine, lamotrigine, or levetiracetam is recommended for children and adults (ILAE level AâC for adults/Cochrane level strong for children and adults). Oxcarbazepine is an alternative for children, although its level A evidence, in a single class I trial, could relate to poor phenytoin tolerability. Eslicarbazepine acetate, lacosamide, and zonisamide are alternatives for adults and gabapentin for the elderly (ILAE level A). Carbamazepine is not a first choice for the elderly due to its high potential for interactions. In generalized epilepsy with tonicâclonic seizures (GTC), lamotrigine, levetiracetam, and sodium valproate are recommended for children and adults (ILAE level CâD/Cochrane level moderateâstrong) although sodium valproate is contraindicated in girls and women of childbearing age unless special considerations are met. Ethosuximide is the first choice in absence epilepsy without GTC (ILAE level A).ConclusionsLamotrigine and levetiracetam can be used as first choice for focal seizures and generalized epilepsy with GTC, suitable in all ageâgroups and for both men and women. Recommendations for GTC seizures have lower evidence than those for focal seizures