levothyroxine (Synthroid, Levoxyl, Levothroid, Unithroid, Levolet, Novothyrox, Thyrotab)

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Introduction

Tradenames: Synthroid, Levoxyl, Levothroid, Unithroid, Levolet, Novothyrox, Thyrotab.[9]

* Generic equally effective as brand name[27]

Epidemiology

Indications

Contraindications

Caution

pregnancy category = a

safety in lactation = ?

Dosage

(replacement dose averages 1.7 ug/kg/day)

switching generics does not require dose adjustment[31]

Tabs: 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200, 300 mg.

Powder for injection: 0.2 mg (10 mL), 0.5 mL (10 mL)

Pharmacokinetics

elimination via liver

Monitor

  • serum TSH
    • baseline then every 6-8 weeks until normal, then every 6-12 months[17]
    • every 6 weeks to 3 months after change is dose or product
    • change in patient health
    • every 4-6 weeks patients > 50 years with cardiac disease
    • every 2-4 weeks patients < 50 years with severe hypothyroidism

Adverse effects

Drug interactions

Mechanism of action

More general terms

Additional terms

Component of

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary
  3. 3.0 3.1 3.2 Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 275
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. 5.0 5.1 5.2 5.3 5.4 Medical Knowledge Self Assessment Program (MKSAP) 11, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2015, 2018, 2023.
  6. Journal Watch 20(14): 114, 2000 Singh N et al Effect of calcium carbonate on the absorption of levothyroxine. JAMA 283:2822, 2000 PMID: https://www.ncbi.nlm.nih.gov/pubmed/10838651
  7. 7.0 7.1 7.2 Journal Watch 21(13):106, 2001 Arafah BM et al Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med 344:1743, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11396440
  8. 8.0 8.1 Prescriber's Letter 10(8):44 2003
  9. 9.0 9.1 Prescriber's Letter 11(10): 2004 Levothyroxine Sustitution Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201013&pb=PRL (subscription needed) http://www.prescribersletter.com
  10. 10.0 10.1 Prescriber's Letter 12(5): 2005 Combination Liothyronine (T3) and Levothyroxine (T4) Supplementation for Hypothyroidism Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210512&pb=PRL (subscription needed) http://www.prescribersletter.com
  11. Roos A, Linn-Rasker SP, van Domburg RT, Tijssen JP, Berghout A. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial. Arch Intern Med. 2005 Aug 8-22;165(15):1714-20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16087818
  12. 12.0 12.1 Centanni M et al, Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med 2006; 354:1787 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16641395
  13. 13.0 13.1 Prescriber's Letter 13(5): 2006 Levothyroxine Absorption in Patients with Reduced Gastric Acid Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220613&pb=PRL (subscription needed) http://www.prescribersletter.com
  14. 14.0 14.1 Lexi-Comp IncTHYROXINE
  15. 15.0 15.1 Prescriber's Letter 15(12): 2008 Drugs and Substances that Reduce Absorption of Levothyroxine Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=241209&pb=PRL (subscription needed) http://www.prescribersletter.com
  16. 16.0 16.1 Bach-Huynh T-G et al Timing of levothyroxine administration affects serum thyrotropin concentration. J Clin Endocrinol Metab 2009 Oct; 94:3905. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19584184
  17. 17.0 17.1 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com18)
  18. 18.0 18.1 Bolk N et al Effects of Evening vs Morning Levothyroxine Intake A Randomized Double-blind Crossover Trial Arch Intern Med. 2010;170(22):1996-2003 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21149757 <Internet> http://archinte.ama-assn.org/cgi/content/abstract/170/22/1996
  19. 19.0 19.1 Turner MR et al Levothyroxine dose and risk of fractures in older adults: nested case-control study BMJ 2011; 342:d2238 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21527461 <Internet> http://www.bmj.com/content/342/bmj.d2238.full
    Leese GP and Flynn RV Levothyroxine dose and fractures in older adults BMJ 2011; 342:d2250 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21527462 <Internet> http://www.bmj.com/content/342/bmj.d2250
  20. Prescriber's Letter 19(11): 2012 Helping Patients Take Levothyroxine Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=281112&pb=PRL (subscription needed) http://www.prescribersletter.com
  21. 21.0 21.1 Deprecated Reference
  22. 22.0 22.1 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  23. 23.0 23.1 Vita R et al. Switching levothyroxine from the tablet to the oral solution formulation corrects the impaired absorption of levothyroxine induced by proton-pump inhibitors. J Clin Endocrinol Metab 2014 Dec; 99:4481 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25259910 <Internet> http://press.endocrine.org/doi/abs/10.1210/jc.2014-2684
  24. 24.0 24.1 Irving SA et al Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol. 2015;82(1):136-141. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25040647
  25. Tahboub R, Arafah BM. Sex steroids and the thyroid. Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):769-80. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19942152
  26. 26.0 26.1 Zamfirescu I, Carlson HE. Absorption of levothyroxine when coadministered with various calcium formulations. Thyroid. 2011 May;21(5):483-6. doi:http://dx.doi.org/ 10.1089/thy.2010.0296. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21595516 Free PMC Article
  27. 27.0 27.1 Brito JP et al. Comparative effectiveness of generic vs brand-name levothyroxine in achieving normal thyrotropin levels. JAMA Netw Open 2020 Sep 30; 3:e2017645 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32997127 PMCID: PMC7527873 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2771041
  28. 28.0 28.1 Brito JP, Ross JS, El Kawkgi OM et al Levothyroxine Use in the United States, 2008-2018. JAMA Intern Med. Published online June 21, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34152370 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2781311
    Silverstein WK, Grady D Overuse of Levothyroxine in Patients With Subclinical Hypothyroidism. Time to "Leve"-Out-Thyroxine. JAMA Intern Med. Published online June 21, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34152358 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2781314
  29. 29.0 29.1 Brito JP et al. Levothyroxine use in the United States, 2008-2018. JAMA Intern Med 2021 Jun 21; PMID: https://www.ncbi.nlm.nih.gov/pubmed/34152370 PMCID: PMC8218227 (available on 2022-06-21) https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2781311
  30. 30.0 30.1 Windle ML Fast Five Quiz: Levothyroxine Medscape. October 7, 2021 https://reference.medscape.com/viewarticle/960226
  31. 31.0 31.1 Brito JP, Deng Y, Ross JS et al. Association between generic-to-generic levothyroxine switching and thyrotropin levels among US adults. JAMA Intern Med 2022 Feb 28; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35226058 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2789278
  32. Medscape: Levothyroxine https://reference.medscape.com/drug/synthroid-levoxyl-levothyroxine-342732

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