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Primary Care

Off label prescribing to children in primary care in Germany: retrospective cohort study

BMJ 2002; 324 doi: https://doi.org/10.1136/bmj.324.7349.1311 (Published 01 June 2002) Cite this as: BMJ 2002;324:1311

Paediatric off label prescribing in Germany

Most problems with current drug prescribing practices in infants and
children arise due to the fact that paediatricians have to rely on
treatment recommendations that include drugs which have not been
adequately studied by the manufacturer in paediatric age groups. These
drugs therefore frequently lack an official licence for paediatric use.
The data presented by Bücheler et al. (BMJ 2002;324:1311-2) somehow
deviate the discussion from this central problem. Their list of most
frequent off label drugs given to outpatients hints to at least five
different putative reasons for the observed prescription practices in the
region of Baden-Württemberg, Germany. These categories are explained using
the following examples:

1. Xylometazoline and oxymetazoline. Every paediatrician and every
pharmacist is aware of the fact that these drugs are available as nasal
drops containing different drug concentrations specifically designed for
different age groups. Thus, off label use of such preparations is not a
necessity; safe alternatives are available. Prescription of an
inappropriate preparation for toddlers might be an indicator of poor
quality of paediatric care by general practitioners which are used to
prescribe nose drops for adults only. Alternatively, – and much more
probably - this class of drugs may be not available for free except for
paediatric age groups. Thus, there may be a continuous temptation
(inherent to the German system of reimbursement) to prescibe these drugs
„off label“ if adult family members need to take them.

2. Tyrothricin and cetylpyridinium. These drugs are of questionable
usefulness and may be substituted without any loss of efficacy by
sweetmeats and lozenges available in the next supermarket. One should not
even attempt to include this class of drugs into a serious discussion of
the actual problems of paediatric drug therapy.

3. Salbutamol and terbutaline. Both beta-2-agonists are explicitly
listed in the official recommendations of the German Society of Pediatric
Pulmonology and the „Deutsche Atemwegsliga“ for the treatment of wheezy
infants. Drug formulations licensed for that specific use are available in
Germany. As a paediatrician I have difficulties to understand the
classification of the prescription as „off label“.

4. Fluticasone propionate. This inhalative steroid is also explicitly
listed in the recommendations for long-term treatment of asthmatic
children between 3 and 5 years of age. Drug formulations are available in
Germany which are licensed for the use in children older than 4 years of
age (probably due to the fact that only one out of eleven published
clinical trials has included children aged <4 years). This might be
evidence of absence or absence of evidence for the efficacy of fluticasone
propionate in 3-4 year old children. It is not easy to understand the
rational basis of this age limit. However, for the sake of scientific
analysis, it would be interesting to know whether all reported cases of
off label use of fluticasone are concerning 3-4 year old children.

5. Sult(h)iame. This drug, according to the web-site of the
manufacturer, „has proven ist value as an antiepileptic drug over
decades“. A Medline search revealed several case reports, clinical trials
and reviews on the use of sulthiame in childhood epilepsy published as
early as in 1968. At least in Germany, sulthiame is considered the drug of
first choice of Rolando epilepsy (benign epilepsy of childhood with
centrotemporal spikes). The drug is licensed in Germany for the use in
patients with focal epilepsy irrespective of their age and specific age-
related dosage recommendations are given in the summary of product
characteristics (Fachinformation). This drug may be used for other (non-
licensed) forms of childhood epilepsy. This might then represent a true
off label use which may require professional control of prescription
practice based on published evidence.

In summary, not every drug prescription classified as being „off
label“ by Bücheler et al. may in fact reflect true paediatric off label
prescriptions as internationally discussed. Also, since the database used
by the authors did not contain diagnoses, they did not identify off label
use of licensed drugs for „unlicensed“ diseases. This might be the reason
why Dr. Banner from Tulsa, Oklahoma, fell into confusion when at first
reading the manuscript.

Thomas Böhler

Paediatrician

MDK Baden-Württemberg,
Adenauerplatz 1,
D-69115 Heidelberg,
Germany

Competing interests: No competing interests

06 June 2002
Thomas Boehler
consulting paediatrician, Medizinischer Dienst der Krankenversicherung Baden-Württemberg
Adenauerplatz 1, D-69115 Heidelberg