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Levothyroxine

Classification: C

Drug products: Eltroxin, Euthyrox, Levaxin 0,1 mg u/lactose, Levaxin utan lactos, Levaxin®, Levothyroxin, Levothyroxine Sodium, Levothyroxine Sodium App, Levotyroxin Nycomed, L-Thyrox HEXAL, L-Thyroxin, L-Thyroxin AL, L-Thyroxin Aventis, L-Thyroxin Henning, L-Thyroxin Henning® Inject, L-Thyroxine Christiaens, SYNTHROID, Tirosint

ATC code: H03AA01

Substances: levothyroxine, levothyroxine sodium, levothyroxine sodium (hydrate)

Summary

The main indication of levothyroxine is hypothyreoidism.

Dosing of levothyroxine is individual and the lowest effective dose should be used. There are studies indicating that women required higher dose than men when measured as mg/kg of ideal weight. During estrogen therapy or pregnancy, increase of dose is usually needed because elevated thyroxine-binding globulin lead to decrease in free thyroxine serum concentration.

Some studies indicate that long term use of levothyroxine may lead to reduction of bone mineral density (BMD) in women, especially in premenopausal women. No changes in BMD in men have been recorded.

Additional information

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding the pharmacokinetics of levothyroxine have been found.A retrospective observational study (69 men, 88 premenopausal women, 91 postmenopausal women) showed that premenopausal women had a greater dose requirement (mg/kg bodyweight) of levothyroxine than men and postmenopausal women [1]. However, a prospective observational study (13 men, 37 women) showed that when ideal body weight instead of actual body weight was used to calculate the dose, all women had a greater dose requirement than men [2].

In women on oral estrogen therapy or pregnant women, adaptation of dosage is necessary because of elevated thyroxine-binding globulin leading to decreased free thyroxine serum concentration [3]. Levothyroxine-treated pregnant women often need to increase the daily dose by 25-30%. Following delivery, levothyroxine dose should be reduced to prepregnancy levels [4].

Effects

See Pharmacokinetics and dosing. No other studies with a clinically relevant sex analysis regarding the effects of levothyroxine have been found.

Adverse effects

A review (in total 3279 patients) described that most cross-sectional studies reported adverse effects at a larger number of bone sites in postmenopausal women, suggesting a negative influence on bone mineral density (BMD) with levothyroxine therapy. However, other cross-sectional studies found comparable results in pre- and postmenopausal women, but no effect of levothyroxine on BMD in men. This review reports no dose-response relationship [5]. The original manufacturer report that long-term levothyroxine therapy might induce decreased BMD in women, particularly postmenopausal women on higher doses [6].

Reproductive health issues

Estrogen can increase the concentration of thyroxine-binding globulin in serum. Women using contraceptives containing estrogen or hormone replacement therapy may require higher doses of levothyroxine [7]. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

A cross-sectional retrospective study (33238 men, 87165 women) examined the relationship between TSH and free T4. In individuals not receiving levothyroxine treatment, free T4 concentrations corresponded to higher median TSH in men than in women [8].

Updated: 2017-03-28

Date of litterature search: 2014-09-12

References

  1. Devdhar M, Drooger R, Pehlivanova M, Singh G, Jonklaas J. Levothyroxine replacement doses are affected by gender and weight, but not age. Thyroid. 2011;21:821-7. PubMed
  2. Jonklaas J. Sex and age differences in levothyroxine dosage requirement. Endocr Pract. 2010;16:71-9. PubMed
  3. Arafah BM. Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med. 2001;344:1743-9. PubMed
  4. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21:1081-125. PubMed
  5. Schneider R, Reiners C. The effect of levothyroxine therapy on bone mineral density: a systematic review of the literature. Exp Clin Endocrinol Diabetes. 2003;111:455-70. PubMed
  6. Levoxyl (levothyroxine). DailyMed [www]. US National Library of Medicine. [updated 2014-05-01, cited 2014-09-12]. länk
  7. LEVAXIN (levotyroxin). Summary of Product Characteristics. Medical Products Agency - Sweden; 2013
  8. Hadlow NC, Rothacker KM, Wardrop R, Brown SJ, Lim EM, Walsh JP. The relationship between TSH and free T₄ in a large population is complex and nonlinear and differs by age and sex. J Clin Endocrinol Metab. 2013;98:2936-43. PubMed
  9. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Authors: Linnéa Karlsson Lind, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson