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Therapeutics Today
June 2016
Number 6
For personal use only. Not to be reproduced without permission of the NMIC.
Has patient inhaler technique improved over time? Inhaled
therapy plays an important role in the management of chronic respiratory
conditions including asthma. Problems with inhaler technique however have
been recognised as a reason for poor control of asthma since the first
pressurised metered-dose inhalers (MDI) were launched in the 1960s. Various
initiatives have been implemented in attempts to improve inhaler technique
including the development of various dry powder inhalers (DPIs), the development of breath-actuated
MDI (BAMDI), the attachment of an inhalation chamber (IC) to the MDI (MDI+IC), and education of
patients and healthcare professionals. A recent systematic review (n=144 articles, involving 54,354
children and adults, with either asthma or COPD) investigated the extent and prevalence of incorrect
inhaler use over 40 years (Chest 2016; doi:10.1016/j.chest.2016.03.041). The review assessed
(1) the most common errors made by patients using the various inhalers, (2) the percentage of
patients demonstrating correct, acceptable or poor technique and (3) the change in these outcomes
over time. The overall results showed a prevalence of correct inhaler technique of 31%, acceptable
technique of 41% and poor technique of 31%.The most frequent errors with the MDI (n=23,720)
were no full expiration before inhalation (48%), errors in co-ordination (45%), in speed and /or depth
of inspiration (44%), and no post-inhalation breath-hold (48%). The most frequent errors with the
DPI (n=21,497) were incorrect preparation (29%), no full expiration before inhalation (46%) and no
post-inhalation breath-hold (37%). The most common error with the BAMDI (n=10,833) was no postinhalation breath-hold (39%) and with the MDI+IC (n=2,432) was difficulty with firing the MDI and
breathing from the chamber (38%). Of interest, there were no significant differences between the
first and second twenty-year periods of the study.
Limitations of this systematic review included the marked diversity in study designs, population
samples and assessment of outcomes of the included studies. However, the authors state that the
results suggest that incorrect inhaler use in patients with asthma and COPD is still high and does not
appear to have improved over 40 years. They recommend that new approaches to education and
drug delivery should be explored.
Risk of pneumonia with inhaled corticosteroids The European
Pharmacovigilance Risk Assessment Committee (PRAC) recently undertook a
review of the known risk of pneumonia associated with inhaled corticosteroids
(ICS) when used to treat chronic obstructive pulmonary disease (COPD)
(http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/n
ews/2016/03/news_detail_002489.jsp&mid=WC0b01ac058004d5c1). The
review also assessed whether there were differences in the risk of pneumonia
between the ICS products. The review confirmed that patients with COPD treated with ICS are at
increased risk of pneumonia; however the benefits of using ICS in these patients outweigh
their risks. It also found that there was no evidence of differences in the risk of pneumonia between
the various ICS products. The review concluded that there is no need to change the way that ICS are
used, however it reminded healthcare professionals and patients that they should always be
vigilant for signs and symptom of pneumonia in patients with COPD, especially those taking
ICS. Risk factors for pneumonia in patients with COPD include current smoking, low BMI and severe
COPD. Further information is available on the Health Products Regulatory Authority (HPRA) and
European Medicines Agency websites: www.hpra.ie and www.ema.europa.eu.
Severe and fatal medicine-related poisoning in young children in the
UK Accidental or “exploratory” ingestion of medicines by young children is a
common reason for seeking urgent medical assessment; fortunately the
majority of these cases do not lead to significant harm. However some
medicines are considered high risk where ingestion of as little as up to 2 times
the adult dose of the medicine could theoretically be fatal for a 10 kg child.
These medicines include tricyclic antidepressants, antipsychotics, quinine, calcium channel
blockers, opioids and oral hypoglycaemic agents. There is a lack of UK epidemiological data
on this topic, therefore national clinical databases were recently analysed in order to identify the
medicines most frequently associated with significant harm to young children (Arch Dis Child
2016;1-4). Data was obtained for the study over different time periods from: (1) death certificates
for children aged ≤4 years (England and Wales only), (2) admissions to paediatric intensive care
units (PICU) related to drug poisoning for children aged ≤4 years, (3) enquiries to the UK Poisons
Information Database (UKPID) for children aged ≤4 years and (4) the Hospital Episode Statistics
(HES) database (which contains details of all admissions to NHS hospitals in England) in order to
identify children aged <14 years with admissions related to medicine poisoning resulting in death
or PICU admission.
The study found that there were 28 deaths occurring in children aged ≤4 years which were
due to pharmaceutical substances from 2001 to 2013. Of these 16 (57%) were due to
methadone, 3 were due to antidepressants and 2 due to heroin; drugs associated with 1 death
each included iron, other opioids and anticonvulsants. There were 201 children aged ≤4 years
admitted to PICU from 2002 to 2012 as a result of medicine-related poisoning; where recorded,
the most common causative agents related to PICU admission were benzodiazepines
(n=22), methadone (n=20), other opioids (n=19), antidepressants (n=13) and iron (n=13).
There were 69 telephone enquiries on the UKPID from 2008 to 2014 related to severe or life
threatening medicine-related poisoning in children aged ≤4 years, of which 68% related to
accidental poisoning and the remainder due to iatrogenic overdose or therapeutic excess. Two
thirds of the UKPID queries related to iron-containing compounds, anticonvulsants,
methadone and tricyclic antidepressants. The HES data found that the annual number of
admissions for medicine-related in children <14 years had fallen for most drugs since 1998/1999.
Of note, a limitation of the study is that the data from the different database sources related to
different time periods and different age ranges. A further limitation of the study is that it was not
possible to differentiate between episodes caused by accidental poisoning and those resulting
from adverse drug reactions and iatrogenic medication error. This might be relevant for some
drugs including antidepressants, iron preparations and anticonvulsants. However the authors
noted that all episodes of methadone toxicity were related to accidental poisoning or
deliberate administration since methadone has no therapeutic role in young children. They
stated that fatal childhood medicine-related poisoning is a rare occurrence and the number of
deaths in this study is consistent with other developed countries. Methadone was the most
common medicine causing fatal poisoning and was a common cause of PICU admission. The
authors advise that patients receiving methadone should be repeatedly informed of the
dangers of methadone to children and be given advice regarding safe storage.
[Editor’s note: The National Poisons Information Centre at Beaumont Hospital Dublin, provides
24-hour information on acute poisoning for healthcare professionals (Telephone 01 8092566)]
The NMIC is on the move! As part of the developments associated with the
building of the new National Children’s Hospital, the NMIC will be relocating within
the St. James’s Hospital campus in late June. We hope to keep any disruptions to
our clinical enquiry answering service to a minimum during this time, however we
ask for patience and understanding should you experience a delay in receiving
information during this time period. Our new address will be the National Medicines Information
Centre, Hospital 1 Middle Floor, St. James’s Hospital. Our telephone and email contact details
remain the same.
Every effort has been made to ensure that this information is correct and is prepared from the best available resources at our disposal at the time of issue. This
newsletter is produced by the National Medicines Information Centre, St. James’s Hospital (SJH) Dublin 8 and Dept of Therapeutics Trinity College, Trinity Centre,
SJH. Tel: Direct Line (01) 473 0589 or 1850 727 727 Email: [email protected] Website: www.nmic.ie