BIOEQUIVALENCE OF GENERIC AND BRAND-NAME LEVOTHYROXINE PRODUCTS IN THE TREATMENT OF HYPOTHYROIDISM

Objective.-To compare relative bioavailability of Synthroid, Levoxine (Levoxine has been renamed Levoxyl), and 2 generic levothyroxine sodiu m 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 chemical ly euthyroid and were receiving levothyroxine sodium, 0.1 or 0.15 mg. Interventions.-All patients received each of the 4 levothyroxine produ cts for 6-week periods in the same dosage as their prestudy regimen wi th no washout period. The order of the drug sequences was randomly det ermined before study initiation. Main Outcome Measures.-Area under the curve, time to peak serum concentrations, and peak serum concentratio ns of thyroxine, triiodothyronine, and free thyroxine index for all 4 products. Results.-All data analyses were completed prior to unblindin g of the product codes. No significant differences between the 4 produ cts were found in area under the curve or peak serum concentrations of total thyroxine, total triiodothyronine, or free thyroxine index, Alt hough Synthroid produced a more rapid rise in total serum triiodothyro nine concentration and a higher total peak serum triiodothyronine conc entration than the other products, these differences were not statisti cally 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 bioequiv alence of 0.95 to 1.07 was demonstrated, tighter than the current bioe quivalence criterion for oral formulations. Conclusions.-The 4 generic and brand-name levothyroxine preparations studied are different but a re bioequivalent by current Food and Drug Administration criteria and are interchangeable in the majority of patients receiving thyroxine re placement therapy. Further investigation is required to determine whet her our results are equally applicable to all existing levothyroxine p reparations.