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Letters to the Editor
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Levothyroxine
Do not suspend levothyroxine
Professor J. H. Perrin, MRPharmS
I have read Kenneth
Bird’s letter (PJ, 6 November, p680) on his
problems with an extemporaneous “suspension” of levothyroxine,
using Keltrol, a polysaccharide gum, giving a neutral solution in water.
Using only the information given in the package insert, Martindale and
the Merck Index it should be obvious not to try to suspend this drug
because of the low dose, and its relative ease of oxidation. In addition,
levothyroxine has a significant solubility in water.
In the reported case what happened to the drug is not obvious but the
low dose would make it especially difficult to obtain uniform quantities
of drug per unit volume. Some or all of the drug may have gone into solution
and some may have become oxidised during preparation and subsequent shaking
of the “suspension”. Was the drug protected from light and
refrigerated? Refrigeration causes solubility and particle size changes,
contributing further to the dangers of this formulation. There are other
possibilities involving the gum. Did the drug bind to the gum, and as
a result was not available for absorption? Or did this potential binding
accelerate the oxidation of the drug, so rendering it inactive?
The correct way to give a fraction of a tablet, other than half a tablet,
is to grind the tablet and weigh out the appropriate amount. Of course
some oxidation is possible during this process and only a few doses should
be prepared at a time. The powder so produced should be “hidden” in
jelly or ice cream immediately before dosing. It can also be mixed with
water immediately before administration via a dropper.
Reading Martindale and speaking with our drug information service (University
of Florida) tells me that the younger the infant the higher the dose
per kilogram becomes. Commercially available doses or half tablets are
usually prescribed. There is a research paper1 stating that levothyroxine
is stable for eight days when protected from light at 4C in a 40 per
cent aqueous glycerol solution. Again, Martindale informs us that the
drug is more soluble in ethanol than water, hence triturating the tablet
with the glycerol before adding the water would be the best method of
effecting solution. Again some oxidation (discoloration) is possible.
Centrifugation would be better than filtration if clarification is deemed
necessary.
J. H. Perrin
Gainesville, Florida
Reference
1. Boulton DW, Fawcett JP, Woods DJ. Stability of an extemporaneously
compounded levothyroxine sodium oral liquid. American Journal of Health-System
Pharmacists 1996;53:1157–6115. |
The
Pharmaceutical Journal