Intended for healthcare professionals


Survey of unlicensed and off label drug use in paediatric wards in European countries

BMJ 2000; 320 doi: (Published 08 January 2000) Cite this as: BMJ 2000;320:79

Use of unlicensed medicines in children

Editor - Over recent years there has been increasing concern
expressed within the medical and pharmaceutical professions, and amongst
the public in general, regarding the fact that few medicines used in
secondary and tertiary care paediatrics are licensed in children. Studies
have been published which indicate that the extent of this problem is very
significant, not just in this country but throughout Europe. A recent
study1 has shown that on general medical wards two thirds of patients
received an unlicensed or off
label drug prescription (421/624;67%) and nearly half of all prescriptions
written were for unlicensed drugs or off-label use (1036/2262;46%).
Previous studies have shown that these figures significantly increase when
high dependency areas are studied2, 3.
Those of us working in paediatrics have been heartened by the fact that
pressure exerted from a number of directions, including the Neonatal and
Paediatric Pharmacists Group (NPPG) and the Royal College of Paediatrics
and Child Health (RCPCH) did seem to be generating a recognition that this
is a serious issue which must be addressed. However in recent weeks we
have had cause to temper our optimism.
On 14th. February this year Dr. David Jackson, the Medical Director of
GlaxoWellcome UK, wrote to the major paediatric centres to inform them of
a decision by the company to discontinue the supply of several unlicensed
tablet preparations which the company had been making available for many
years. The drugs concerned are Imuran, Lanvis, Puri-Nethol and Myleran.
Pharmacists will immediately appreciate that such preparations are used in
the treatment of some of the most sick children in our care.
Subsequently, a letter was sent to Dr. Jackson co-signed by the Chair of
the Paediatric Oncology Pharmacists (POP) group and the Secretary of the
UK Child Cancer Study Group (UKCCSG) expressing concern on behalf of the
paediatric community at this decision, which had been taken without any
discussions with the professions concerned. A number of points were made
to him explaining why it was felt that the discontinuation of these
problems would pose significant difficulties to clinicians and pharmacists
in the areas of organ and bone marrow transplantation, and cancer
Dr. Jackson's reply offered no hope that the decision to withdraw these
products would be reconsidered. But it was the reason given for the
decision which causes us such concern for the future. It appears that
UK has decided, as a matter of corporate policy, not to continue to supply
unlicensed medicines. In an increasingly regulated world this may seem
entirely reasonable. But the crucial point is that, in the cases of Puri-
Nethol and Lanvis in particular, these products have been used within
Medical Research Council (MRC) protocols, adopted on a national basis, for
the treatment of acute lymphoblastic leukaemia (ALL) in children since the
early 1980's. With some 400 children being diagnosed with ALL every year
the UK, GlaxoWellcome had the opportunity to use the wealth of data
collected on a potential population of at least 6,000 patients as the
basis for an application to license these two products.
Yet it chose not to do so, and instead will withdraw these two products on
completion of the current ALL study. The problems we are faced with
following the withdrawal of Myleran are more acute. Supplies of 25mg.
tablets are no longer available yet we have bone marrow transplant
patients requiring daily doses of 4mg/kg. as part of their conditioning
regime. The difficulty in administering such doses using 2mg. tablets are
obvious, but
there was the added advantage that we could make a suspension from crushed
25mg. tablets for those children would could not take tablets. This will
now be impossible due to the bulk of the powder containing the same doses
2mg. tablets.
If a company with the resources of GlaxoWellcome is unwilling to seek to
license products used in children for which there is overwhelming evidence
of efficacy in large numbers of patients, there seems to be little hope
other suppliers will seek to license their products. In the absence of any
immediately apparent options for compelling suppliers to license their
products in children, recent experience would suggest that the pressure to
license medicines in children may have the opposite effect to that which
was intended.

Nigel Ballantine,
Specialist Clinical Pharmacist, Haematology

1. Conroy S, et al. Survey of unlicensed and off-label drug use
in paediatric wards in European countries. BMJ 2000;320:79-88.

2. Turner S, et al. Use of "off-label" and unlicensed drugs in
paediatric intensive care units. Lancet 1996;347:549-50.

3. Conroy S, et al. Unlicensed and off label drug use in the
neonate. Arch Dis Child Fetal Neonatal Ed 1999;80:F142-5.

Birmingham Children's Hospital NHS Trust,
Steelhouse lane,
B14 7NS.

Competing interests: No competing interests

17 July 2000
Nigel Ballantine