Timing of breakfast does not influence therapeutic efficacy of liquid levothyroxine formulation
- 400 Downloads
Oral levothyroxine (L-T4) is the mainstay of hypothyroidism treatment. Many factors may influence its absorption, including the timing of administration. Objective of the study is to demonstrate the therapeutic equivalence of administering liquid L-T4 with breakfast or 10 min before breakfast. This was a pilot study conducted with a crossover design AB/BA where A stays for L-T4 with breakfast and B for L-T4 10 min before breakfast. A post hoc analysis was conducted to compare L-T4 administered at breakfast or 10 min before breakfast with L-T4 administered 30 min before breakfast. Sixty-one hypothyroid patients were enrolled and assigned to one of the two treatment sequences. All patients were evaluated for TSH levels at the end of each period. Fifty-nine patients completed the study. The mean thyrotropin concentration was 1.52 ± 0.73 µU/ml when L-T4 was administered with breakfast and 1.46 ± 0.81 µU/ml when it was taken 10 min before breakfast, without clinically and statistically significant differences (P = 0.59), regardless of treatment sequence and period. The mean thyrotropin concentration was 1.54 ± 0.9 µU/ml when L-T4 was administered at 0–10 min intervals before breakfast and 1.25 ± 0.7 µU/ml when it was taken 30 min before breakfast (ratio = 1.23, within our definition of equivalence set at 0.8–1.25). There is therapeutic equivalence between liquid L-T4 administration at breakfast or 10 min before breakfast. We can also hypothesize that there are no clinically relevant differences between liquid L-T4 administration 30 min before breakfast or at shorter intervals.
KeywordsLevothyroxine Oral solution Hypothyroidism Replacement therapy TSH Therapeutic equivalence
The authors would like to thank the nurse team (Nadia Biccari, Alberto Pambianco, and Lorena Urbani) of the Endocrine Clinic at the Department of Medicine, University of Perugia, for their excellent assistance. This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.L.H. Fish, H.L. Schwartz, J. Cavanaugh, M.W. Steffes, J.P. Bantle, J.H. Oppenheimer, Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans. N. Engl. J. Med. 316, 764–770 (1987)CrossRefPubMedGoogle Scholar
- 10.F. Santini, A. Pinchera, A. Marsili, G. Ceccarini, M.G. Castagna, R. Valeriano, M. Giannetti, D. Taddei, R. Centoni, G. Scartabelli, T. Rago, C. Mammoli, R. Elisei, P. Vitti, Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases. J. Clin. Endocrinol. Metab. 90, 124–127 (2005)CrossRefPubMedGoogle Scholar
- 19.M. Torlontano, C. Durante, I. Torrente, U. Crocetti, G. Augello, G. Ronga, T. Montesano, L. Travascio, A. Verrienti, R. Bruno, S. Santini, P. D’Arcangelo, B. Dallapiccola, S. Filetti, V. Trischitta, Type 2 deiodinase polymorphism (threonine 92 alanine) predicts L-thyroxine dose to achieve target thyrotropin levels in thyroidectomized patients. J. Clin. Endocrinol. Metab. 93, 910–913 (2008)CrossRefPubMedGoogle Scholar
- 20.K.A. Heemstra, H.C. Hoftijzer, W.M. van der Deure, R.P. Peeters, E. Fliers, B.C. Appelhof, W.M. Wiersinga, E.P. Corssmit, T.J. Visser, J.W. Smit, Thr92Ala polymorphism in the type 2 deiodinase is not associated with T4 dose in athyroid patients or patients with Hashimoto thyroiditis. Clin. Endocrinol. 71, 279–283 (2009)CrossRefGoogle Scholar
- 31.M.P. Vanderpump, W.M. Tunbridge, J.M. French, D. Appleton, D. Bates, F. Clark, J. Grimley Evans, D.M. Hasan, H. Rodgers, F. Tunbridge, E.T. Young, The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin. Endocrinol. 43, 55–68 (1995)CrossRefGoogle Scholar
- 33.J.G. Hollowell, N.W. Staehling, W.D. Flanders, W.H. Hannon, E.W. Gunter, C.A. Spencer, L.E. Braverman, Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 87, 489–499 (2002)CrossRefPubMedGoogle Scholar
- 35.J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick, R. Pessah-Pollack, P.A. Singer, K.A. Woeber, American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 18, 988–1028 (2012)CrossRefPubMedGoogle Scholar
- 36.M.I. Surks, E. Ortiz, G.H. Daniels, C.T. Sawin, N.F. Col, R.H. Cobin, J.A. Franklyn, J.M. Hershman, K.D. Burman, M.A. Denke, C. Gorman, R.S. Cooper, N.J. Weissman, Subclinical thyroid disease. Scientific review and guidelines for diagnosis and management. JAMA 291, 228–238 (2004)CrossRefPubMedGoogle Scholar
- 39.I. Walter-Sack, C. Clanget, R. Ding, C. Goeggelmann, V. Hinke, M. Lang, J. Pfeilschifter, Y. Tayrouz, K. Weqscheider, Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures. Clin. Pharmacokinet. 43, 1037–1053 (2004)CrossRefPubMedGoogle Scholar