E-drug: Tablet-splitting with FDCs (esp. antiretrovirals)
-------------------------------------------------------------------------
Dear e-druggers,
In the course of working on an article on fixed-dose combination
antiretrovirals for next week's issue of 'HIV & AIDS Treatment in
Practice' (deadline: next Wednesday, 26 March), I've been
challenged on a claim that combination tablets should not be split,
e.g. for paediatric dosing, because the distribution of the active
ingredients between the portions of the tablet is too variable.
The products I'm interested in are mainly dual-drug combinations
such as Combivir, Duovir, Virocomb or Zidolam
(zidovudine/lamivudine), and Lamivir or Lamistar
(stavudine/lamivudine). Apart from Combivir (a GSK product), these
are Indian generic products not licensed in Europe or North America
(although Virocomb, from Ranbaxy, appears on the WHO Essential
Drugs and Medicines list of pre-qualified products for international
licensing/purchase/distribution).
Does anyone know of relevant research on such formulations (not
necessarily with the same active ingredients) which has sought to
find out whether this problem is real and practical or only
theoretical?
The need to split tablets seems to arise most strongly in paediatric
HIV treatment, because:
* syrup formulations are very expensive (for reasons of market
size)
* most young children are orphans with no-one to pay for their
treatment
* most of the very young children have anaemia and can't tolerate
zidovudine and there isn't an available syrup formulation for
stavudine, and
* the fixed dose combination tablets are the most economical form
in which these drugs are available.
My questions include:
Is the distribution of active ingredients within tablets likely to vary
from brand to brand and between combinations of different
quantities of different active ingredients?
Is it likely to be more of a problem with stavudine (30mg or 40mg
of active ingredient per tablet) versus zidovudine (300mg) or
lamivudine (150mg)?
How far is the opinion that tablets cannot safely be split based on
experimental foundations (people splitting tablets and measuring the
distribution of active ingredients) versus theoretical foundations (not
being able to guarantee that the active ingredients are evenly mixed
or evenly deposited when made up into tablets)?
Any help anyone can give me either in terms of direct answers or
suggesting others I might contact would be very much appreciated.
Yours sincerely,
Julian Meldrum
International Editor, www.aidsmap.com
NAM, Lincoln House, 1 Brixton Road, London SW9 6DE, England
+44 (0)20 7840 0061 (direct line)
+44 (0)20 7840 0050 (switchboard)
+44 (0)20 7735 5351 (fax)
NAM is the specialist HIV information provider, working in
partnership with the International HIV/AIDS Alliance, offering a
global service - including a directory of organisations -- through
www.aidsmap.com
Sign up for our free newsletter 'HIV & AIDS Treatment in Practice'
and/or the weekly bulletin on what's new at aidsmap.com, at:
http://www.aidsmap.com/components/subscribe.asp
--
To send a message to E-Drug, write to: e-drug@usa.healthnet.org
To subscribe or unsubscribe, write to: majordomo@usa.healthnet.org
in the body of the message type: subscribe e-drug OR unsubscribe e-drug
To contact a person, send a message to: e-drug-help@usa.healthnet.org
Information and archives: http://www.essentialdrugs.org/edrug