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Treatment pattern and frequency of serum TSH measurement in users of different levothyroxine formulations: a population-based study during the years 2009–2015

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Abstract

Background

Several conditions can modify the intestinal absorption of levothyroxine tablets, with potential consequences on their therapeutic effect. Pre-dosed ampoules and oral drops have been recently made available to overcome this limitation.

Aims

To describe the pattern of use of different formulations of levothyroxine in a general population of Southern Italy and to perform an exploratory analysis investigating the effect of switching from levothyroxine tablets to oral liquid formulations.

Methods

Data were extracted from the Caserta Local Health Unit database. All patients receiving at least one levothyroxine prescription during the years 2009–2015 were identified. 1-year incidence of use of formulation-specific levothyroxine was calculated. Switchers between levothyroxine tablets and oral liquid formulations were identified and the frequency of thyroid-stimulating hormone measurement within 2 years prior and after the switch date was explored.

Results

Overall, 56,354 levothyroxine users were included in the study. Of these, 55,147 patients received at least one prescription for tablets (97.9%), 1867 pre-dosed ampoules (3.3%) and 1550 oral drops (2.8%). The proportion of levothyroxine users receiving oral liquid formulations slightly increased over time. Patients switching from tablets to oral liquid formulations showed a statistically significant reduction in the number of thyroid-stimulating hormone measurements after switching from tablets, especially in presence of drugs interacting with levothyroxine potentially altering its absorption.

Conclusions

Use of levothyroxine oral liquid formulations is increasing over time even though their use is still limited in a general population of Southern Italy. Our exploratory analysis showed that the frequency of thyroid-stimulating hormone measurement was reduced in patients switching from levothyroxine tablet to new formulations.

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References

  1. J. Jonklaas, A.C. Bianco, A.J. Bauer, K.D. Burman, A.R. Cappola, F.S. Celi, D.S. Cooper, B.W. Kim, R.P. Peeters, M.S. Rosenthal, A.M. Sawka, American Thyroid Association Task Force on Thyroid Hormone Replacement, Guidelines for the treatment of hypothyroidism prepared by the American thyroid association task force on thyroid hormone replacement. Thyroid. (2014). doi:10.1089/thy.2014.0028

  2. 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 Adult, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Prac. 18, 988–1028 (2012)

    Article  Google Scholar 

  3. A. Latina, D. Gullo, F. Trimarchi, S. Benvenga, Hashimoto’s thyroiditis: similar and dissimilar characteristics in neighboring areas. Possible implications for the epidemiology of thyroid cancer. PLoS One (2013). doi:10.1371/journal.pone.0055450

  4. P.R. Larsen, H.M. Kronenberg, S. Melmed, K.S. Polonsky Williams Textbook of Endocrinology, 10th edn. (Elsevier, 2003)

  5. S. Benvenga, When thyroid hormone replacement is ineffective? Curr. Opin. Endocrinol. Diabetes Obes. 20, 467–477 (2013)

    Article  CAS  PubMed  Google Scholar 

  6. P. Colucci, C. Seng Yue, M. Ducharme, S. Benvenga, A review of the pharmacokinetics of levothyroxine for the treatment of hypothyroidism. Eur. Endocrinol. 9, 40–47 (2013)

    Article  Google Scholar 

  7. R. Vita, P. Fallahi, A. Antonelli, S. Benvenga, The administration of L-thyroxine as soft gel capsule or liquid solution. Expert. Opin. Drug. Deliv. 11, 1103–1111 (2014)

    Article  CAS  PubMed  Google Scholar 

  8. C.G. Roberts, P.W. Ladenson: Hypothyroidism. Lancet (2004). doi:10.1016/S0140-6736(04)15696-1

  9. P.V. Eligar, V.S. Eligar, Levothyroxine: factors affecting its intestinal absorption and metabolism. West Lond. Med. J. 3, 9–14 (2011)

    Google Scholar 

  10. S.A. Irving, T. Vadiveloo, G.P. Lees: Drugs that interact with levothyroxine: an observational study from the thyroid epidemiology. audit and research study (TEARS). Clin. Endocrinol. (2015). doi:10.1111/cen.12559

  11. C. Abi-Abib Rde, M. Vaisman, Is it necessary to increase the dose of levothyroxine in patients with hypothyroidism who use omeprazole? Arq. Bras. Endocrinol. Metabol. 58, 731–736 (2014)

    Article  PubMed  Google Scholar 

  12. G. Ianiro, F. Mangiola, T.A. Di Rienzo, S. Bibbò, F. Franceschi, A.V. Greco, A. Gasbarrini, Levothyroxine absorption in health and disease, and new therapeutic perspectives. Eur. Rev. Med. Pharmacol. Sci. 18, 451–456 (2014)

    CAS  PubMed  Google Scholar 

  13. D. Pabla, F. Akhlaghi, H. Zia, A comparative pH-dissolution profile study of selected commercial levothyroxine products using inductively coupled plasma mass spectrometry. Eur. J. Pharm. Biopharm. 72, 105–110 (2009)

    Article  CAS  PubMed  Google Scholar 

  14. A. Cassio, S. Monti, A. Rizzello, I. Bettocchi, F. Baronio, G. D’Addabbo, M.O. Bal, A. Balsamo, Comparison between liquid and tablet formulations of levothyroxine in the initial treatment of congenital hypothyroidism. J. Pediatr. 162, 1264–1269 (2013)

    Article  CAS  PubMed  Google Scholar 

  15. C. Virili, P. Trimboli, F. Romanelli, M. Centanni: Liquid and softgel levothyroxine use in clinical practice: state of the art. Endocrine (2016). doi:10.1007/s12020-016-1035-1

  16. World Health Organisation. ATC/DDD Index 2016, http://www.whocc.no/atc_ddd_index. Accessed 24 Mar 2015

  17. G. Trifirò, S. Corrao, M. Alacqua, S. Moretti, M. Tari, A.P. Caputi, V. Arcoraci; UVEC Group, Interaction risk with proton pump inhibitors in general practice: significant disagreement between different drug-related information sources. Br. J. Clin. Pharmacol. 62, 582–590 (2006). doi:10.1111/j.1365-2125.2006.02687.x

    Article  PubMed  PubMed Central  Google Scholar 

  18. C. Ferrajolo, V. Arcoraci, M.G. Sullo, C. Rafaniello, L. Sportiello, R. Ferrara, A. Cannata, C. Pagliaro, M.G. Tari, A.P. Caputi, F. Rossi, G. Trifirò, A. Capuano: Pattern of statin use in southern italian primary care: can prescription databases be used for monitoring long-term adherence to the treatment? PLoS One (2014). doi:10.1371/journal.pone.0102146

  19. C. Rafaniello, V. Arcoraci, C. Ferrajolo, L. Sportiello, M.G. Sullo, F. Giorgianni, G. Trifirò, M. Tari, A.P. Caputi, F. Rossi, K. Esposito, D. Giugliano, A. Capuano: Trends in the prescription of antidiabetic medications from 2009 to 2012 in a general practice of Southern Italy: a population-based study. Diabetes. Res. Clin. Pract. (2015). doi:10.1016/j.diabres.2014.12.007

  20. M. Alacqua, G. Trifirò, L. Cavagna, R. Caporali, C.M. Montecucco, S. Moretti, D.U. Tari, M. Galdo, A.P. Caputi, V. Arcoraci, Prescribing pattern of drugs in the treatment of osteoarthritis in Italian general practice: the effect of rofecoxib withdrawal. Arthritis Rheum. 59, 568–574 (2008)

    Article  PubMed  Google Scholar 

  21. G. Trifirò, M. Alacqua, S. Corrao, S. Moretti, D.U. Tari, M. Galdo; UVEC Group, A.P. Caputi, V. Arcoraci, Lipid lowering drug use in Italian primary care: effects of reimbursement criteria revision. Eur. J. Clin. Pharmacol. 64, 619–625 (2008)

    Article  PubMed  Google Scholar 

  22. G. Trifirò, R. Savica, L. Morgante, N. Vanacore, M. Tari, S. Moretti, M. Galdo, E. Spina, A.P. Caputi, V. Arcoraci, Prescribing pattern of anti-Parkinson drugs in Southern Italy: cross-sectional analysis in the years 2003–2005. Parkinsonism Relat. Disord. 14, 420–425 (2008)

    Article  PubMed  Google Scholar 

  23. G. Trifirò, F. Parrino, J. Sultana, F. Giorgianni, C. Ferrajolo, E. Bianchini, G. Medea, S. Benvenga, I. Cricelli, C. Cricelli, F. Lapi: Drug interactions with levothyroxine therapy in patients with hypothyroidism: observational study in general practice. Clin. Drug Investig. (2015). doi:10.1007/s40261-015-0271-0

  24. D. Italiano, A. Capuano, A. Alibrandi, R. Ferrara, A. Cannata, G. Trifirò, J. Sultana, C. Ferrajolo, M. Tari, D.U. Tari, M. Perrotta, C. Pagliaro, C. Rafaniello, E. Spina, V. Arcoraci: Indications of newer and older anti-epileptic drug use: findings from a southern Italian general practice setting from 2005-2011. Br. J. Clin. Pharmacol. (2015) doi:10.1111/bcp.12577

  25. P. Fallahi, S.M. Ferrari, S. Marchi, N. De Bortoli, I. Ruffilli, A. Antonelli: Patients with lactose intolerance absorb liquid levothyroxine better than tablet levothyroxine. Endocrine (2016) doi:10.1007/s12020-016-1090-7

  26. I. Pirola, A.M. Formenti, E. Gandossi, F. Mittempergher, C. Casella, B. Agosti, C. Cappelli, Oral liquid L-thyroxine (L-T4) may be better absorbed compared to L-T4 tablets following bariatric surgery. Obes. Surg. 23, 1493–1496 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  27. E. Peroni, M.C. Vigone, S. Mora, L.A. Bassi, C. Pozzi, A. Passoni, G. Weber: Congenital hypothyroidism treatment in infants: a comparative study between liquid and tablet formulations of levothyroxine. Horm. Res. Paediatr. (2014). doi:10.1159/000356047

  28. C. Cappelli, R. Negro, I. Pirola, E. Gandossi, B. Agosti, M. Castellano, Levothyroxine liquid solution versus tablet form for replacement treatment in pregnant women. Gynecol. Endocrinol 20, 1–3 (2015). doi:10.3109/09513590.2015.1113518

    Google Scholar 

  29. C. Cappelli, I. Pirola, L. Daffini, E. Gandossi, B. Agosti, M. Castellano: Thyroid hormonal profile in elderly patients treated with two different levothyroxine formulations: a single institute survey. Eur. Geriatr. Med. (2014). doi:10.1016/j.eurger.2014.09.006

  30. M. Feghali, R. Venkataramanan, S. Caritis: Pharmacokinetics of drugs in pregnancy. Semin. Perinatol. (2015). doi:10.1053/j.semperi.2015.08.003

  31. P. Fallahi, S.M. Ferrari, I. Ruffilli, A. Antonelli: Reversible normalisation of serum TSH levels in patients with autoimmune atrophic gastritis who received L-T4 in tablet form after switching to an oral liquid formulation: a case series. BMC Gastroenterol. (2016). doi:10.1186/s12876-016-0439-y

  32. P. Fallahi, S.M. Ferrari, S. Camastra, U. Politti, I. Ruffilli, R. Vita, G. Navarra, S. Benvenga, A. Antonelli: TSH normalization in bariatric surgery patients after the switch from L-Thyroxine in tablet to an oral liquid formulation. Obes. Surg. (2016). doi:10.1007/s11695-016-2247-4

  33. L. Pirola, E. Daffini, D. Gandossi, A. Lombardi, M. Formenti, M. Castellano, C. Cappelli: Comparison between liquid and tablet levothyroxine formulations in patients treated through enteral feeding tube. J. Endocrinol. Invest. (2014). doi:10.1007/s40618-014-0082-9

  34. R. Vita, P. Fallahi, A. Antonelli, S. Benvenga, The administration of L-thyroxine as soft gel capsule or liquid solution. Exp. Opin. Drug Deliv. 11, 1103–1111 (2014)

    Article  CAS  Google Scholar 

  35. R. Negro, R. Valcavi, D. Agrimi, K.A. Toulis: Levothyroxine liquid solution versus tablet for replacement treatment in hypothyroid patients. Endocr. Pract. (2014). doi:10.4158/EP13378.OR

  36. P. Fallahi, S.M. Ferrari, A. Antonelli, Oral L-thyroxine liquid versus tablet in patients with hypothyroidism without malabsorption: a prospective study. Endocrine 52, 597–601 (2016)

    Article  CAS  PubMed  Google Scholar 

  37. M.G. Santaguida, C. Virili, S.C. Del Duca, M. Cellini, I. Gatto, N. Brusca, C. De Vito, L. Gargano, M. Centanni: Thyroxine softgel capsule in patients with gastric-related T4 malabsorption. Endocrine (2015) doi:10.1007/s12020-014-0476-7

  38. D. Ribichini, G. Fiorini, A. Repaci, V. Castelli, L. Gatta, D. Vaira, R. Pasquali: Tablet and oral liquid L-thyroxine formulation in the treatment of naïve hypothyroid patients with Helicobacter pylori infection. Endocrine (2016) doi:10.1007/s12020-016-1167-3

  39. P. Fallahi, S.M. Ferrari, A. Antonelli: In patients with subclinical hypothyroidism while in therapy with tablet L-T4, the liquid L-T4 formulation is more effective in restoring euthyroidism. Endocr. Pract. (2016) doi:10.4158/EP161545.OR

  40. C.P. Lombardi, R. Bocale, A. Barini, A. Barini, A. D’Amore, M. Boscherini, R. Bellantone: Comparative study between the effects of replacement therapy with liquid and tablet formulations of levothyroxine on mood states, self-perceived psychological well-being and thyroid hormone profile in recently thyroidectomized patients. Endocrine (2016) doi:10.1007/s12020-016-1003-9

  41. Agenzia Italiana del Farmaco (AIFA- Italian Drug Agency). OsMed 2015 Drug Utilisation Report, http://www.agenziafarmaco.gov.it/sites/default/files/Rapporto_OsMed_2015__AIFA.pdf. Accessed 25 Jan 2016

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Acknowledgements

This study was supported with unconditional grant by IBSA Farmaceutici Italia s.r.l. The sponsor was not involved in the protocol drafting, data analysis and interpretation of study results.

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Authors and Affiliations

  1. Unit of Clinical Pharmacology, Academic Hospital G. Martino, Messina, Italy

    Rosarita Ferrara, Valentina Ientile, Vincenzo Arcoraci, Carlo Piccinni & Gianluca Trifirò

  2. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    Vincenzo Arcoraci & Salvatore Benvenga

  3. Department of Experimental Medicine, Second University of Naples, Naples, Italy

    Carmen Ferrajolo

  4. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

    Carlo Piccinni

  5. Unit of Biostatistics, IRCCS “Casa Sollievo della Sofferenza”, San Giovanni Rotondo (FG), Italy

    Andrea Fontana

  6. Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Messina, Italy

    Gianluca Trifirò

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  1. Rosarita Ferrara
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  2. Valentina Ientile
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Correspondence to Gianluca Trifirò.

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The authors declare that they have no competing interests.

Informed consent

The informed consent was not required as the data utilized were collected retrospectively during routine clinical practice. This study did not involve direct patient contact. All data used was fully anonymised. As a result, the Ethics Committee of the University Hospital of Messina (A.O.U. G. Martino Hospital) does not require ethical approval.

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Ferrara, R., Ientile, V., Arcoraci, V. et al. Treatment pattern and frequency of serum TSH measurement in users of different levothyroxine formulations: a population-based study during the years 2009–2015. Endocrine 58, 143–152 (2017). https://doi.org/10.1007/s12020-017-1242-4

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  • DOI: https://doi.org/10.1007/s12020-017-1242-4

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