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Letters to the Editor
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Excipients
Problems with excipients and Smith Lemli Opitz syndrome
From Mr A. J. Nunn, FRPharmS, and others
Most medicines contain excipients in order to improve palatability, to
confer stability and to improve shelf life.
The potential adverse effects of some of these excipients (particularly
colouring agents and antimicrobial preservatives) are well known. Many
parents believe that these agents contribute to behavioural problems in
their children and seek to avoid them.1
Rarely do pharmacists know which products contain particular excipients
unless alerted to a problem requiring investigation of the formulation.
Recently a boy of 15 years (the son of RH) with Smith Lemli Opitz syndrome
(a rare inborn error of cholesterol metabolism) was changed from extemporaneously
prepared chloral hydrate (containing only the active ingredient, syrup
and water) to Welldorm Elixir (containing chloral hydrate with saccharin,
sodium benzoate, flavouring and colours Ponceau 4R E124 and Sunset Yellow
E110). He had been maintained on a diet free of additives where possible
and there were no other medication changes. Coincident with medication
change was a significant deterioration in his behaviour which included
hyperactivity, aggression and self-harm. He redeveloped photosensitivity,
had recurrent infections and increased appetite. He was thoroughly investigated
but no disease-related explanation could be determined. Withdrawal of Welldorm
Elixir and replacement with excipient-free chloral hydrate produced a slow
return to normal behaviour over several months. Brief rechallenge with
Welldorm Elixir produced deterioration again. He is currently being investigated
for temporal lobe epilepsy.
When asked if chloral hydrate syrup and Welldorm Elixir are equivalent,
many pharmacists would first consider the equivalence of the active ingredient
and might not consider the contribution of excipients unless they know
that the patient is likely to have a problem with them.
Pharmaceutical excipients, well tolerated by the majority of patients,
may produce significant adverse effects in a small minority. When asked
questions about the equivalence of preparations, pharmacists should enquire
whether the patient has allergies or sensitivities to foods or excipients.
With drugs such as chloral hydrate, which are non-specific with regard
to a main diagnosis, seeking further information about the patient’s
diagnosis may alert pharmacists to the need for further investigation.
Smith Lemli Opitz syndrome is a rare inherited illness which will be unknown
to many pharmacists and doctors. There is a deficiency of 7-dehydrocholesterol
reductase with accumulation of 7-dehydrocholesterol and deficiency of cholesterol
unless substituted. Patients with this syndrome will have suffered cellular
damage through lack of cholesterol and exposure to high levels of cholesterol
precursors in utero. Autistic spectrum and behaviour disturbances may be
part of the syndrome.2 The case history of this child suggests that excipients
may have triggered a change in behaviour.
Further information about the Smith Lemli Opitz syndrome can be obtained
here
Anthony Nunn
Reginald Hunter
Steven Ryan
Royal Liverpool Children’ NHS Trust
References
1. Pawar S, Kumar A. Issues in the formulation of drugs for oral use
in children — role of excipients. Pediatric Drugs 2002;4:371–9.
2. Scriver CR, Beaudet AL, Sly WS, Valle D (editors). Smith Lemli Opitz
syndrome. In: The metabolic and molecular basis of inherited disease
(8th ed). McGraw Hill; 2001. pp6183–201. |
The
Pharmaceutical Journal