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Safety
Dangers when preparing children’s medicines
From Dr J. H. Perrin, MRPharmS
The flavouring of children’s medicines, supposedly to increase compliance,
is common in the US and Canada. A wide variety of flavours is available.
Flavouring usually involves changing a solid dosage form into a liquid
medicine, so creating an unapproved new medicine. Manufactured tablets,
or capsules, are often the source of the active ingredients. The new medicine
may be a solution or a suspension, or, as is frequently the case, a mixture
of the two. This raises numerous questions involving the stability and
biopharmaceutical parameters of the new medicine. What interactions occur,
both in vitro and in vivo, between the drug and the new ingredients? This
information is desirable for all possible combinations of drugs and flavours.
The worst example is probably that of flavouring Augmentin1,2. By changing
the solubility of the clavulanate or the pH of the product slightly, from
that of the commercial product, significant amounts of the inhibitor can
be destroyed in a few hours. Many a US parent has overpaid for what, at
best, is a suspension of amoxicillin.
This brings up the issue of whether or not to refrigerate. Cooling alters
the ratio of suspended to solubilised, and the cooling and warming cycles
normally increase the suspended particle size, hence bioavailablity may
be reduced, etc. These issues have been discussed in the PJ concerning
the compounding of
levothyroxine (20 November 2004, p748).
In practice, many US pharmacists do not start with a dosage form as the
source of active ingredient, but obtain the raw chemical entity from various
supply houses, even if the drug is still on patent. Clearly the legal manufacturer
is not the source of this “pure” active. Illegal importation
of chemicals of questionable origin and quality may be involved. Are there
infringements of patents and trademarks involved here? How many UK pharmacists
are prepared to tell a parent “It looks lovely and it tastes lovely,
but it has not been tested for quality or performance”? How many
UK physicians or veterinarians are prepared to write prescriptions for
such unapproved new medicines? Who would want to insure pharmacists or
prescribers involved in such practices? Surely not the cash-strapped NHS
or diligent insurance companies.
When I wrote the articles1,2 I talked to several nurses around the US who
are said to be experts in administering drugs to infants. They never mentioned
flavours, but did talk of discipline, and of the ease of “hiding” any
medicine in jelly or ice cream. The advantage of this is that there is
minimal disturbance of the manufactured dosage form, and the medicine is
prepared immediately before administration.
Finally, what kind of errors are introduced when weight and other measurements
are involved in the preparation of a compounded medicine? A recent Food
and Drug Administration study of a range of medicines produced in compounding
pharmacies found that more than 25 per cent contained concentrations of
active ingredients outside acceptable tolerances of the stated amount.3 The errors were always on the low side. The Medicines and Healthcare products
Regulatory Agency and the Royal Pharmaceutical Society have the opportunity
to stop a problem before it becomes a bigger problem. I know that other
agencies wish that they had had the same opportunity.
John Perrin
Gainesville,
Florida
References
1. Perrin, JH. Disastrous reflavoring of antibiotics (letter). Pediatrics
1997;100:420
2. Perrin, JH. Pediatrician and compounding pharmacist: a dangerous liaison.
Archives of Pediatrics and Adolescent Medicine. 1996;150:224–6
3. Center for Drug Evaluation and Research. Report: limited
FDA survey of compounded drug products. US Food and Drug Administration. |
The
Pharmaceutical Journal