Skip to main content

Advertisement

SpringerLink
Log in

Generic levothyroxine initiation and substitution among Medicare and Medicaid populations: a new user cohort study

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

Generic levothyroxine has been approved and available since 2004 but its substitution remains controversial. Therefore, the objective was to examine patterns of and identify factors associated with initiation and substitution of generic levothyroxine treatment.

Methods

This was a retrospective observational study, including new users of brand and generic levothyroxine in 2013–2015 Medicare (n = 15,877) or 2011–2012 Medicaid (n = 9390) administrative claim databases. The primary outcomes included (1) generic levothyroxine initiation, and (2) among brand-new users, generic levothyroxine substitution in 12 months. The factors associated with generic levothyroxine initiation and substitution were measured.

Results

Among all levothyroxine new users, Medicare beneficiaries had a higher proportion of generic levothyroxine initiation than Medicaid beneficiaries (66.40% vs. 44.04%, respectively). Medicare beneficiaries’ demographic factors, and health service utilizations were associated with generic levothyroxine initiation. Medicaid beneficiaries who were male and residing in the northeast region and rural areas were more likely to initiate generic levothyroxine. Among brand levothyroxine new users, the generic substitution rate was higher in the Medicare than the Medicaid cohort (18.26 vs. 3.88%). Medicare brand levothyroxine new users’ demographic factors and health service utilizations were associated with generic levothyroxine substitution. Medicaid brand levothyroxine new users who were residing in the northeast region, with more prior hospitalization, and initiating a lower dosage of brand levothyroxine, had higher rates of generic substitution.

Conclusion

Patient demographic factors and health service utilizations are associated with generic levothyroxine initiation and substitution. Educational outreach programs targeted to increase generic levothyroxine use and prescription savings should be tailored based on different patient populations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. M.P. Vanderpump, The epidemiology of thyroid disease. Br. Med. Bull. 99, 39–51 (2011). https://doi.org/10.1093/bmb/ldr030

    Article  PubMed  Google Scholar 

  2. Y. Aoki, R.M. Belin, R. Clickner, R. Jeffries, L. Phillips, K.R. Mahaffey, Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002). Thyroid 17(12), 1211–1223 (2007). https://doi.org/10.1089/thy.2006.0235

    Article  PubMed  Google Scholar 

  3. B.O. Asvold, L.J. Vatten, T. Bjoro, Changes in the prevalence of hypothyroidism: the HUNT study in Norway. Eur. J. Endocrinol. 169(5), 613–620 (2013). https://doi.org/10.1530/eje-13-0459

    Article  CAS  PubMed  Google Scholar 

  4. 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(2), 489–499 (2002). https://doi.org/10.1210/jcem.87.2.8182

    Article  CAS  PubMed  Google Scholar 

  5. H.J. Baskin, R.H. Cobin, D.S. Duick, H. Gharib, R.B. Guttler, M.M. Kaplan, R.L. Segal, American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr. Pract. 8(6), 457–469 (2002)

    Article  Google Scholar 

  6. 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, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr. Pract. 18(6), 988–1028 (2012). https://doi.org/10.4158/ep12280.gl

    Article  PubMed  Google Scholar 

  7. AACE, TES, and ATA joint position statement on the use and interchangeability of thyroxine products. Thyroxine Products Joint Position Statement. https://www.thyroid.org/thyroxine-products-joint-position-statement/. (2004)

  8. American Thyroid Association, The Endocrine Society and American Association of Clinical Endocrinologists. Joint statement on the U.S. Food and Drug Administration’s decision regarding bioequivalence of levothyroxine sodium. Thyroid. 14(7), 486 (2004). https://doi.org/10.1089/1050725041517138

  9. S. Benvenga, A. Carlé, Levothyroxine formulations: pharmacological and clinical implications of generic substitution. Adv. Ther. 36(Suppl 2), 59–71 (2019)

  10. H.B. Burch, K.D. Burman, D.S. Cooper, J.V. Hennessey, A 2013 survey of clinical practice patterns in the management of primary hypothyroidism. J. Clin. Endocrinol. Metab. 99(6), 2077–2085 (2014). https://doi.org/10.1210/jc.2014-1046

    Article  CAS  PubMed  Google Scholar 

  11. GPhA, Generic Drug Savings in the U.S. Seventh Annual Edition. (GPhA, 2015). http://www.gphaonline.org/media/wysiwyg/PDF/GPhA_Savings_Report_2015.pdf

  12. R.G. Frank, The ongoing regulation of generic drugs. N. Engl. J. Med. 357(20), 1993–1996 (2007). https://doi.org/10.1056/NEJMp078193

    Article  CAS  PubMed  Google Scholar 

  13. (AAM) TAfAM. Generic Drug Access & Savings Report. (2018). https://accessiblemeds.org/sites/default/files/2018_aam_generic_drug_access_and_savings_report.pdf

  14. J.N. Howard, I. Harris, G. Frank, Z. Kiptanui, J. Qian, R. Hansen, Influencers of generic drug utilization: a systematic review. Res. Soc. Adm. Pharm. 14(7), 619–627 (2018). https://doi.org/10.1016/j.sapharm.2017.08.001

    Article  Google Scholar 

  15. B.R. Troy, The 10 most-prescribed and top-selling medications. (2015). https://www.webmd.com/drug-medication/news/20150508/most-prescribed-top-selling-drugs

  16. R.J. Romanelli, V. Nimbal, S.K. Dutcher, X. Pu, J.B. Segal, Provider and patient determinants of generic levothyroxine prescribing: an electronic health records-based study. Ann. Pharmacother. 51(8), 640–648 (2017). https://doi.org/10.1177/1060028017705393

    Article  PubMed  Google Scholar 

  17. M.A. Raebel, J. Schmittdiel, A.J. Karter, J.L. Konieczny, J.F. Steiner, Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases. Med. Care 51, S11–S21 (2013). https://doi.org/10.1097/MLR.0b013e31829b1d2a

    Article  PubMed  PubMed Central  Google Scholar 

  18. US Census Bureau 2010 ZIP Code Tabulation Area (ZCTA) Relationship File Layouts and Contents. Geography. (US Census Bureau). https://www.census.gov/geo/maps-data/data/zcta_rel_layout.html. Accessed 21 Aug 2018

  19. R.L. Kravitz, R.M. Epstein, M.D. Feldman, C.E. Franz, R. Azari, M.S. Wilkes, L. Hinton, P. Franks, Influence of patients’ requests for direct-to-consumer advertised antidepressants: a randomized controlled trial. JAMA 293(16), 1995–2002 (2005). https://doi.org/10.1001/jama.293.16.1995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. J.J. Gagne, J.M. Polinski, A.S. Kesselheim, N.K. Choudhry, D. Hutchins, O.S. Matlin, A. Tong, W.H. Shrank, Patterns and predictors of generic narrow therapeutic index drug use among older adults. J. Am. Geriatrics Soc. 61(9), 1586–1591 (2013). https://doi.org/10.1111/jgs.12399

    Article  Google Scholar 

  21. W.H. Shrank, N.K. Choudhry, J. Agnew-Blais, A.D. Federman, J.N. Liberman, J. Liu, A.S. Kesselheim, M.A. Brookhart, Fischer MAJHa, State generic substitution laws can lower drug outlays under. Medicaid 29(7), 1383–1390 (2010)

    Google Scholar 

  22. M.A. Fischer, J. Avorn, Economic consequences of underuse of generic drugs: evidence from medicaid and implications for prescription drug benefit plans. Health Serv. Res. 38(4), 1051–1064 (2003). https://doi.org/10.1111/1475-6773.00162

    Article  PubMed  PubMed Central  Google Scholar 

  23. K. Sewell, S. Andreae, E. Luke, M.M. Safford, Perceptions of and barriers to use of generic medications in a rural African American population, Alabama, 2011. Preventing Chronic Dis. 9, E142 (2012). https://doi.org/10.5888/pcd9.120010

    Article  Google Scholar 

  24. A. Iosifescu, E.A. Halm, T. McGinn, A.L. Siu, A.D. Federman, Beliefs about generic drugs among elderly adults in hospital-based primary care practices. Patient Educ. Couns. 73(2), 377–383 (2008). https://doi.org/10.1016/j.pec.2008.07.012

    Article  PubMed  PubMed Central  Google Scholar 

  25. A.L. Hulbert, N.A. Pilch, D.J. Taber, K.D. Chavin, P.K. Baliga, Generic immunosuppression: deciphering the message our patients are receiving. Ann. Pharmacother. 46(5), 671–677 (2012). https://doi.org/10.1345/aph.1R028

    Article  PubMed  Google Scholar 

  26. A.D. Federman, E.A. Halm, A.L. Siu, Use of generic cardiovascular medications by elderly medicare beneficiaries receiving generalist or cardiologist care. Med. Care 45(2), 109–115 (2007). https://doi.org/10.1097/01.mlr.0000250293.24939.2e

    Article  PubMed  Google Scholar 

  27. R. Tamblyn, P. McLeod, J.A. Hanley, N. Girard, J. Hurley, Physician and practice characteristics associated with the early utilization of new prescription drugs. Med Care 41(8), 895–908 (2003). https://doi.org/10.1097/01.mlr.0000078145.41828.3e

    Article  PubMed  Google Scholar 

  28. S.H. Kaplan, S. Greenfield, B. Gandek, W.H. Rogers, J.E. Ware Jr, Characteristics of physicians with participatory decision-making styles. Ann. Intern. Med. 124(5), 497–504 (1996)

    Article  CAS  Google Scholar 

  29. D.L. Roter, M. Stewart, S.M. Putnam, M. Lipkin Jr, W. Stiles, T.S. Inui, Communication patterns of primary care physicians. JAMA 277(4), 350–356 (1997)

    Article  CAS  Google Scholar 

  30. A. Omojasola, B. Gor, L. Jones, Perceptions of generic drug discount programs among low-income women: a qualitative study. Womens Health issues 23(1), e55–e60 (2013). https://doi.org/10.1016/j.whi.2012.10.002

    Article  PubMed  Google Scholar 

  31. P. Amstislavski, A. Matthews, S. Sheffield, A.R. Maroko, J. Weedon, Medication deserts: survey of neighborhood disparities in availability of prescription medications. Int. J. Health Geogr. 11, 48 (2012). https://doi.org/10.1186/1476-072x-11-48

    Article  PubMed  PubMed Central  Google Scholar 

  32. S. Benvenga, When thyroid hormone replacement is ineffective? Curr. Opin. Endocrinol. Diabetes, Obes. 20(5), 467–477 (2013). https://doi.org/10.1097/MED.0000000000000003

    Article  CAS  Google Scholar 

  33. P.N. Taylor, A. Iqbal, C. Minassian, A. Sayers, M.S. Draman, R. Greenwood, W. Hamilton, O. Okosieme, V. Panicker, S.L. Thomas, Falling threshold for treatment of borderline elevated thyrotropin levels–balancing benefits and risks: evidence from a large community-based study. JAMA Intern. Med. 174(1), 32–39 (2014)

    Article  CAS  Google Scholar 

  34. P. dos Santos Vigário, F. Vaisman, C.M. Coeli, L. Ward, H. Graf, G. Carvalho, R.M. Júnior, M. Vaisman, Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life–a Brazilian multicentre study. Endocrine 44(2), 434–440 (2013)

    Article  Google Scholar 

  35. M. Katz, J. Scherger, S. Conard, L. Montejano, S. Chang, Healthcare costs associated with switching from brand to generic levothyroxine. Am. Health Drug Benefits 3(2), 127–134 (2010)

    PubMed  PubMed Central  Google Scholar 

  36. S. Benvenga, F. Di Bari, R. Vita, Undertreated hypothyroidism due to calcium or iron supplementation corrected by oral liquid levothyroxine. Endocrine 56(1), 138–145 (2017)

    Article  CAS  Google Scholar 

  37. A. Roos, S.P. Linn-Rasker, R.T. van Domburg, J.P. Tijssen, A. Berghout, The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch. Intern. Med. 165(15), 1714–1720 (2005)

    Article  CAS  Google Scholar 

Download references

Funding

Funding for this paper was made possible, in part, by the U.S. Food and Drug Administration (FDA) grant # U01FD005875. The views expressed in written materials or publications, and by speakers and moderators, do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

Author contributions

JQ and NH had full access to all the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: JQ, LC, RAH, IH, ZW and SKD. Acquisition, analysis, or interpretation of data: JQ, NH, LC, CL and AUM. Drafting of the paper: NH and JQ. Critical revision of the paper for important intellectual content: All authors. Statistical analysis: NH, LC and AUM. Obtained funding: JQ, RAH, IH and ZK. Administrative, technical, or material support: JQ and LC. Study supervision: JQ.

Author information

Authors and Affiliations

  1. Auburn University Harrison School of Pharmacy, Auburn, AL, USA

    Nan Huo, Ahmed Ullah Mishuk, Chao Li, Richard A. Hansen & Jingjing Qian

  2. Department of Medicine, Indiana University School of Medicine, Indianapolis, IL, USA

    Li Chen

  3. IMPAQ International LLC, Columbia, MD, USA

    Ilene Harris & Zippora Kiptanui

  4. Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA

    Zhong Wang

  5. Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA

    Sarah K. Dutcher

Authors
  1. Nan Huo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed Ullah Mishuk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard A. Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ilene Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zippora Kiptanui
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Zhong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sarah K. Dutcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jingjing Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jingjing Qian.

Ethics declarations

Conflict of interest

In the past 3 years, RAH has provided expert testimony for Daiichi Sankyo and Takeda. ZW and SKD are employed by the US FDA, Center for Drug Evaluation and Research. No other authors declare a potential conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huo, N., Chen, L., Ullah Mishuk, A. et al. Generic levothyroxine initiation and substitution among Medicare and Medicaid populations: a new user cohort study. Endocrine 68, 336–348 (2020). https://doi.org/10.1007/s12020-020-02211-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-020-02211-w

Keywords

Search

Navigation