Жидкий левотироксин: вопросы и ответы

Левотироксин (L-Т4) является препаратом с узким терапевтическим диапазоном. И даже небольшое изменение дозы может привести как к недостатку, так и к его передозировке. Существующие на сегодняшний день таблетированные формы L-T4 с широким спектром дозировок обеспечивают достижение и удержание эутиреоза у многих пациентов. Вместе с тем нередко пациенты с гипотиреозом находятся в декомпенсации. На сегодняшний день в мире применяются не только таблетки, но и другие формы L-T4, в том числе гель-капсулы и жидкая форма. В представленном обзоре обсуждаются особенности фармакокинетики, преимущества и недостатки применяемых форм L-T4. Также обсуждаются факторы, влияющие на биодоступность и определяющие дозу L-T4.

1. Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-751. doi: https://doi.org/10.1089/thy.2014.0028

2. Okosieme O, Gilbert J, Abraham P, et al. Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee. Clin Endocrinol (Oxf ). 2016;84(6):799-808. doi: https://doi.org/10.1111/cen.12824

3. Safer DJ. Overprescribed Medications for US Adults: Four Major Examples. J Clin Med Res. 2019;11(9):617-622. doi: https://doi.org/10.14740/jocmr3906

4. NHS. Prescription Cost Analysis—England 2017 2018 [cited 2019 March, 19]. https://digital.nhs.uk/data-and-information/publications/statistical/prescription-cost-analysis/prescription-costanalysisengland-2017

5. Janett-Pellegri C, Wildisen L, Feller M, et al. Prevalence and factors associated with chronic use of levothyroxine: A cohort study. PLoS One. 2021;16(12):e0261160. doi: https://doi.org/10.1371/journal.pone.0261160

6. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160(4):526-34. doi: https://doi.org/10.1001/archinte.160.4.526

7. Taylor PN, Iqbal A, Minassian C, et al. Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study. JAMA Intern Med. 2014;174(1):32-9. doi: https://doi.org/10.1001/jamainternmed.2013.11312

8. Yavuz DG, Yazıcı D, Keskin L, et al. Out-of-Reference Range Thyroid-Stimulating Hormone Levels in Levothyroxine-Treated Primary Hypothyroid Patients: A Multicenter Observational Study. Front Endocrinol (Lausanne). 2017;8:215. doi: https://doi.org/10.3389/fendo.2017.00215

9. Molewijk E, Fliers E, Dreijerink K, et al. Quality of life, daily functioning, and symptoms in hypothyroid patients on thyroid replacement therapy: A Dutch survey. J Clin Transl Endocrinol. 2024;35:100330. doi: https://doi.org/10.1016/j.jcte.2024.100330

10. Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med. 2002;137(11):904-14. doi: https://doi.org/10.7326/0003-4819-137-11-200212030-00011

11. Paul TL, Kerrigan J, Kelly AM, et al. Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women. JAMA. 1988;259(21):3137-41. doi: https://doi.org/10.1001/jama.1988.03720210027023

12. Thayakaran R, Adderley NJ, Sainsbury C, et al. Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: longitudinal study. BMJ. 2019;366:l4892. doi: https://doi.org/10.1136/bmj.l4892

13. Somwaru LL, Arnold AM, Joshi N, Fried LP, Cappola AR. High frequency of and factors associated with thyroid hormone over-replacement and under-replacement in men and women aged 65 and over. J Clin Endocrinol Metab. 2009. doi: https://doi.org/10.1210/jc.2008-1696

14. Virili C, Antonelli A, Santaguida MG, Benvenga S, Centanni M. Gastrointestinal Malabsorption of Thyroxine. Endocr Rev. 2019;40(1):118-136. doi: https://doi.org/10.1210/er.2018-00168

15. Castellana M, Castellana C, Giovanella L, Trimboli P. Prevalence of gastrointestinal disorders having an impact on tablet levothyroxine absorption: should this formulation still be considered as the first-line therapy? Endocrine. 2020;67(2):281-290. doi: https://doi.org/10.1007/s12020-019-02185-4

16. McMillan M, Rotenberg KS, Vora K, et al. Comorbidities, Concomitant Medications, and Diet as Factors Affecting Levothyroxine Therapy: Results of the CONTROL Surveillance Project. Drugs R D. 2016;16(1):53-68. doi: https://doi.org/10.1007/s40268-015-0116-6

17. Benvenga S, Papi G, Antonelli A. Refractory Hypothyroidism Due to Improper Storage of Levothyroxine Tablets. Front Endocrinol (Lausanne). 2017;8:155. doi: https://doi.org/10.3389/fendo.2017.00155

18. Мануйлова Ю.А., Моргунова Т.Б., Фадеев В.В. Причины неэффективности заместительной терапии первичного гипотиреоза. // Клиническая и экспериментальная тиреоидология. — 2019. — Т. 15. — № 1. — С. 12-18. doi: https://doi.org/10.14341/ket10163

19. Bornikowska K, Gietka-Czernel M, Raczkiewicz D, et al. Improvements in Quality of Life and Thyroid Parameters in Hypothyroid Patients on Ethanol-Free Formula of Liquid Levothyroxine Therapy in Comparison to Tablet LT4 Form: An Observational Study. J Clin Med. 2021;10(22):5233. doi: https://doi.org/10.3390/jcm10225233

20. Seng Yue C, Scarsi C, Bettazzi E, et al. Proton Pump Inhibitors Do Not Affect the Bioavailability of a Novel Liquid Formulation of Levothyroxine. Endocr Pract. 2024;30(6):513-520. doi: https://doi.org/10.1016/j.eprac.2024.03.388

21. Yannovits N, Zintzaras E, Pouli A, et al. A bioequivalence study of levothyroxine tablets versus an oral levothyroxine solution in healthy volunteers. Eur J Drug Metab Pharmacokinet. 2006;31(2):73-8. doi: https://doi.org/10.1007/BF03191122

22. Bernareggi A, Grata E, Pinorini MT, Conti A. Oral liquid formulation of levothyroxine is stable in breakfast beverages and may improve thyroid patient compliance. Pharmaceutics. 2013;5(4):621-33. doi: https://doi.org/10.3390/pharmaceutics5040621

23. Yue CS, Scarsi C, Ducharme MP. Pharmacokinetics and potential advantages of a new oral solution of levothyroxine vs. other available dosage forms. Arzneimittelforschung. 2012;62(12):631-6. doi: https://doi.org/10.1055/s-0032-1329951

24. Cappelli C, Pirola I, Daffini L, et al. A Double-Blind Placebo-Controlled Trial of Liquid Thyroxine Ingested at Breakfast: Results of the TICO Study. Thyroid. 2016;26(2):197-202. doi: https://doi.org/10.1089/thy.2015.0422

25. Cappelli C, Pirola I, Daffini L, Gandossi E, Agosti B, Castellano M. Thyroid hormonal profile in elderly patients treated with two different levothyroxine formulations: A single institute survey. Eur Geriatr Med. 2014;5(6):382-385. doi: https://doi.org/10.1016/j.eurger.2014.09.006

26. Negro R, Valcavi R, Agrimi D, Toulis KA. Levothyroxine liquid solution versus tablet for replacement treatment in hypothyroid patients. Endocr Pract. 2014;20(9):901-6. doi: https://doi.org/10.4158/EP13378.OR

27. Markantes GK, Dimitropoulos K, Mamali I, et al. Therapeutic Equivalence of a New Preparation of Liquid Levothyroxine with Tablets in Patients with Overt Primary Hypothyroidism. Eur Thyroid J. 2021;10(1):59-64. doi: https://doi.org/10.1159/000508216. Erratum in: Eur Thyroid J. 2021;10(1):100. doi: https://doi.org/10.1159/000509965

28. Benvenga S, Di Bari F, Vita R. Undertreated hypothyroidism due to calcium or iron supplementation corrected by oral liquid levothyroxine. Endocrine. 2017;56(1):138-145. doi: https://doi.org/10.1007/s12020-017-1244-2

29. Virili C, Giovanella L, Fallahi P, et al. Levothyroxine Therapy: Changes of TSH Levels by Switching Patients from Tablet to Liquid Formulation. A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2018;9:10. doi: https://doi.org/10.3389/fendo.2018.00010

30. Guglielmi R, Grimaldi F, Negro R, et al. Shift from Levothyroxine Tablets to Liquid Formulation at Breakfast Improves Quality of Life of Hypothyroid Patients. Endocr Metab Immune Disord Drug Targets. 2018;18(3):235-240. doi: 10.2174/1871530318666180125155348.