Deprescribing in Patients of Hypothyroidism Results in Better Health Outcome: A Case Series
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Abstract
Appropriate levothyroxine (LT4) dosing is essential in hypothyroid patients to maintain biochemical and clinical euthyroidism, but achieving appropriate plasma concentration of LT4 can be complicated by numerous disease states, foods, supplements, and commonly prescribed medications such as calcium supplements, pantoprazole etc. that potentially interfere with intestinal LT4 absorption. About one-third of treated patients are not receiving adequate treatment, leading to decreased quality of life, increased morbidity, and even increased mortality. Hypothyroid patients treated with LT4 must be careful to avoid concomitant ingestion of such medicines or optimal gap must be ensured between ingestions to prevent drug-drug interactions and reduce absorption of LT4. We describe two such real life cases managed in our clinical pharmacology consultation facility to highlight the importance of systematically evaluating the drug-drug interactions of levothyroxine with commonly used concomitant medications and how deprescribing of the same can result in attainment of optimum thyroid replacement with lesser doses of LT4 with better patient outcome.
1. Asvold BO, Vatten LJ, Bjoro T. Changes in the prevalence of hypothyroidism: the HUNT Study in Norway. Eur J Endocrinol. 2013;169:613–620.
2. Garmendia Madariaga A, Santos Palacios S, Guillen-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014;99:923–931.
3. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977;7:481–493.
4. 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;18:235–240.
5. Elmor R, Sandulli W, Carter CA. The economic impact of changing levothyroxine formulations in difficult-to-treat hypothyroid patients: an evidence-based model. Pharmacoeconomics. 2017;2:1–10.
6. Hennessey JV. The emergence of levothyroxine as a treatment for hypothyroidism. Endocrine. 2017;55:6–18.
7. 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;24:1670–1751.
8. Brenta G, Vaisman M, Sgarbi JA, et al. Clinical practice guidelines for the management of hypothyroidism. Arq Bras Endocrinol Metabol. 2013;57:265–291.
9. Tamargo J, Le Heuzey JY, Mabo P. Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide. Eur J Clin Pharmacol. 2015;71:549–567.
10. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18:988–1028.
11. Toward Optimized Practice (TOP) Endocrine Working Group. Investigation and management of primary thyroid dysfunction clinical practice guideline. Edmonton, AB: Toward Optimized Practice. 2014. http://www.topalbertadoctors.org. Accessed 3 Jun 2022.
12. Malaty W. Primary hypothyroidism. 2017. https://bestpractice.bmj.com/topics/en-us/535/pdf/535.pdf. Accessed 4 Jan 2022.
13. Ott J, Promberger R, Kober F, et al. Hashimoto’s thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter. Thyroid. 2011;21:161–167.
14. Shin YW, Choi YM, Kim HS, et al. Diminished quality of life and increased brain functional connectivity in patients with hypothyroidism after total thyroidectomy. Thyroid. 2016;26:641–649.
15. Vigario Pdos S, Vaisman F, Coeli CM, et al. Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life-a Brazilian multicentre study. Endocrine. 2013;44:434–440.
16. Thvilum M, Brandt F, Almind D, et al. Excess mortality in patients diagnosed with hypothyroidism: a nationwide cohort study of singletons and twins. J Clin Endocrinol Metabol. 2013;98:1069–1075.
17. Kraut E, Farahani P. A systematic review of clinical practice guidelines’ recommendations on levothyroxine therapy alone versus combination therapy (LT4 plus LT3) for hypothyroidism. Clin Invest Med. 2015;38:E305–E313.
18. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390:1550–1562.
19. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283:2822-2825.
20. Zamfirescu I, Carlson HE. Absorption of levothyroxine when coadministered with various calcium formulations. Thyroid. 2011;21(5):483-486.
21. Singh N, Weisler SL, Hershman JM. The acute effect of calcium carbonate on the intestinal absorption of levothyroxine. Thyroid. 2001;11:967-971.
22. Mazokopakis EE, Giannakopoulos TG, Starakis IK. Interaction between levothyroxine and calcium carbonate. Can Fam Physician. 2008;54(1):39.
23. Csako G, McGriff NJ, Rotman-Pikielny P, et al. Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders. Ann Pharmacother. 2001;35(12):1578-1583.
24. Butner LE, Fulco PP, Feldman G. Calcium carbonate-induced hypothyroidism. Ann Intern Med. 2000;132(7):595.
25. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA. 1998;279(10):750.
26. A Irving S, Vadiveloo T, Leese GP. Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol (Oxf). 2015;82(1):136-141.
27. Diskin CJ, Stokes TJ, Dansby LM, et al. Effect of phosphate binders upon TSH and L-thyroxine dose in patients on thyroid replacement. Int Urol Nephrol. 2007;39(2):599-602.
28. Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med. 2006;354(17):1787-1795.
29. Sachmechi I, Reich DM, Aninyei M, Wibowo F, Gupta G, Kim PJ. Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract. 2007;13(4):345-349.
30. Irving SA, Vadiveloo T, Leese GP. Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol (Oxf). 2015;82(1):136-141.
31. Dietrich JW, Gieselbrecht K, Holl RW, Boehm BO. Absorption kinetics of levothyroxine is not altered by proton-pump inhibitor therapy. Horm Metab Res. 2006;38(1):57-59.
32. Ananthakrishnan S, Braverman LE, Levin RM, Magnani B, Pearce EN. The effect of famotidine, esomeprazole, and ezetimibe on levothyroxine absorption. Thyroid. 2008;18(5):493-498.
33. Abi-Abib Rde C, Vaisman M. Is it necessary to increase the dose of levothyroxine in patients with hypothyroidism who use omeprazole? Arq Bras Endocrinol Metabol. 2014;58(7):731-736.
34. Vita R, Saraceno G, Trimarchi F, Benvenga S. 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;99(12):4481-4486.
2. Garmendia Madariaga A, Santos Palacios S, Guillen-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014;99:923–931.
3. Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977;7:481–493.
4. 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;18:235–240.
5. Elmor R, Sandulli W, Carter CA. The economic impact of changing levothyroxine formulations in difficult-to-treat hypothyroid patients: an evidence-based model. Pharmacoeconomics. 2017;2:1–10.
6. Hennessey JV. The emergence of levothyroxine as a treatment for hypothyroidism. Endocrine. 2017;55:6–18.
7. 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;24:1670–1751.
8. Brenta G, Vaisman M, Sgarbi JA, et al. Clinical practice guidelines for the management of hypothyroidism. Arq Bras Endocrinol Metabol. 2013;57:265–291.
9. Tamargo J, Le Heuzey JY, Mabo P. Narrow therapeutic index drugs: a clinical pharmacological consideration to flecainide. Eur J Clin Pharmacol. 2015;71:549–567.
10. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18:988–1028.
11. Toward Optimized Practice (TOP) Endocrine Working Group. Investigation and management of primary thyroid dysfunction clinical practice guideline. Edmonton, AB: Toward Optimized Practice. 2014. http://www.topalbertadoctors.org. Accessed 3 Jun 2022.
12. Malaty W. Primary hypothyroidism. 2017. https://bestpractice.bmj.com/topics/en-us/535/pdf/535.pdf. Accessed 4 Jan 2022.
13. Ott J, Promberger R, Kober F, et al. Hashimoto’s thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter. Thyroid. 2011;21:161–167.
14. Shin YW, Choi YM, Kim HS, et al. Diminished quality of life and increased brain functional connectivity in patients with hypothyroidism after total thyroidectomy. Thyroid. 2016;26:641–649.
15. Vigario Pdos S, Vaisman F, Coeli CM, et al. Inadequate levothyroxine replacement for primary hypothyroidism is associated with poor health-related quality of life-a Brazilian multicentre study. Endocrine. 2013;44:434–440.
16. Thvilum M, Brandt F, Almind D, et al. Excess mortality in patients diagnosed with hypothyroidism: a nationwide cohort study of singletons and twins. J Clin Endocrinol Metabol. 2013;98:1069–1075.
17. Kraut E, Farahani P. A systematic review of clinical practice guidelines’ recommendations on levothyroxine therapy alone versus combination therapy (LT4 plus LT3) for hypothyroidism. Clin Invest Med. 2015;38:E305–E313.
18. Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet. 2017;390:1550–1562.
19. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283:2822-2825.
20. Zamfirescu I, Carlson HE. Absorption of levothyroxine when coadministered with various calcium formulations. Thyroid. 2011;21(5):483-486.
21. Singh N, Weisler SL, Hershman JM. The acute effect of calcium carbonate on the intestinal absorption of levothyroxine. Thyroid. 2001;11:967-971.
22. Mazokopakis EE, Giannakopoulos TG, Starakis IK. Interaction between levothyroxine and calcium carbonate. Can Fam Physician. 2008;54(1):39.
23. Csako G, McGriff NJ, Rotman-Pikielny P, et al. Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders. Ann Pharmacother. 2001;35(12):1578-1583.
24. Butner LE, Fulco PP, Feldman G. Calcium carbonate-induced hypothyroidism. Ann Intern Med. 2000;132(7):595.
25. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA. 1998;279(10):750.
26. A Irving S, Vadiveloo T, Leese GP. Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol (Oxf). 2015;82(1):136-141.
27. Diskin CJ, Stokes TJ, Dansby LM, et al. Effect of phosphate binders upon TSH and L-thyroxine dose in patients on thyroid replacement. Int Urol Nephrol. 2007;39(2):599-602.
28. Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, Helicobacter pylori infection, and chronic gastritis. N Engl J Med. 2006;354(17):1787-1795.
29. Sachmechi I, Reich DM, Aninyei M, Wibowo F, Gupta G, Kim PJ. Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract. 2007;13(4):345-349.
30. Irving SA, Vadiveloo T, Leese GP. Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS). Clin Endocrinol (Oxf). 2015;82(1):136-141.
31. Dietrich JW, Gieselbrecht K, Holl RW, Boehm BO. Absorption kinetics of levothyroxine is not altered by proton-pump inhibitor therapy. Horm Metab Res. 2006;38(1):57-59.
32. Ananthakrishnan S, Braverman LE, Levin RM, Magnani B, Pearce EN. The effect of famotidine, esomeprazole, and ezetimibe on levothyroxine absorption. Thyroid. 2008;18(5):493-498.
33. Abi-Abib Rde C, Vaisman M. Is it necessary to increase the dose of levothyroxine in patients with hypothyroidism who use omeprazole? Arq Bras Endocrinol Metabol. 2014;58(7):731-736.
34. Vita R, Saraceno G, Trimarchi F, Benvenga S. 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;99(12):4481-4486.
| Files | ||
| Issue | Vol 10, No 4 (Autumn 2022) | |
| Section | Case Report(s) | |
| DOI | https://doi.org/10.18502/jpc.v10i4.11589 | |
| Keywords | ||
| Hypothyroidism Levothyroxine Deprescribing Drug-Drug Interaction | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mishra P, Bhargava S. Deprescribing in Patients of Hypothyroidism Results in Better Health Outcome: A Case Series. J Pharm Care. 2022;10(4):248-253.
