Bioequivalence of generic and brand-name levothyroxine products in the treatment of hypothyroidism
B. J. Dong, W. W. Hauck, J. G. Gambertoglio, L. Gee, J. R. White, J. L. Bubp and F. S. Greenspan
Department of Clinical Pharmacy, University of California Medical Center, San Francisco 94143-0622, USA.
OBJECTIVE: To compare relative bioavailability of Synthroid, Levoxine
(Levoxine has been renamed Levoxyl), and 2 generic levothyroxine sodium
preparations. DESIGN: Single-blind (primary investigators blinded),
randomized, 4-way crossover trial. SETTING: Ambulatory care. PATIENTS:
Twenty-two women with hypothyroidism who were clinically and chemically
euthyroid and were receiving levothyroxine sodium, 0.1 or 0.15 mg.
INTERVENTIONS: All patients received each of the 4 levothyroxine products
for 6-week periods in the same dosage as their prestudy regimen with no
washout period. The order of the drug sequences was randomly determined
before study initiation. MAIN OUTCOME MEASURES: Area under the curve, time
to peak serum concentrations, and peak serum concentrations of thyroxine,
triiodothyronine, and free thyroxine index for all 4 products. RESULTS: All
data analyses were completed prior to unblinding of the product codes. No
significant differences between the 4 products were found in area under the
curve or peak serum concentrations of total thyroxine, total
triiodothyronine, or free thyroxine index. Although Synthroid produced a
more rapid rise in total serum triiodothyronine concentration and a higher
total peak serum triiodothyronine concentration than the other products,
these differences were not statistically significant (P=.08). The Food and
Drug Administration criterion for relative bioequivalence within 90%
confidence intervals (0.8-1.25) was demonstrated (P<.05) for all pairs
of products. Relative bioequivalence of 0.95 to 1.07 was demonstrated,
tighter than the current bioequivalence criterion for oral formulations.
CONCLUSIONS: The 4 generic and brand-name levothyroxine preparations
studied are different but are bioequivalent by current Food and Drug
Administration criteria and are interchangeable in the majority of patients
receiving thyroxine replacement therapy. Further investigation is required
to determine whether our results are equally applicable to all existing
levothyroxine preparations.
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