Description

Simple

A medication used to treat patients with low levels of thyroid hormone.

Clinical

A synthetic T4 hormone used to treat hypothyroidism that can be used along with surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer.

Overview

Levothyroxine is a synthetically produced form of thyroxine, a major endogenous hormone secreted by the thyroid gland.[13] Also known as L-thyroxine or the brand name product Synthroid, levothyroxine is used primarily to treat hypothyroidism, a condition where the thyroid gland is no longer able to produce sufficient quantities of the thyroid hormones T4 (tetraiodothyronine or thyroxine) and T3 (triiodothyronine or [DB00279]), resulting in diminished down-stream effects of these hormones. Without sufficient quantities of circulating thyroid hormones, symptoms of hypothyroidism begin to develop such as fatigue, increased heart rate, depression[4], dry skin and hair, muscle cramps, constipation, weight gain, memory impairment, and poor tolerance to cold temperatures.[14,Read more

Pharmacology

Indication

Levothyroxine is indicated as replacement therapy in primary (thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired hypothyroidism. It is also indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyr... Read more

Pharmacodynamic

Oral levothyroxine is a synthetic hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present.

Levothyroxine has a narrow therapeutic index and is titrated to maintain a euthyroid state with TSH (thyroi... Read more

Mechanism of action

Levothyroxine is a synthetically prepared levo-isomer of the thyroid hormone thyroxine (T4, a tetra-iodinated tyrosine derivative) that acts as a replacement in deficiency syndromes such as hypothyroidism. T4 is the major hormone secreted from the thyroid gland and is chemicall... Read more

Absorption

Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80% with the majority of the levothyroxine dose absorbed from the jejunum and upper ileum. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans, mi... Read more

Protein binding

Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) and albumin (TBA). The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance and lo... Read more

Volume of distribution

Information currently not available.

Clearance

Information currently not available.

Half life

T4 half-life is 6 to 7 days. T3 half-life is 1 to 2 days.[14]

Route of elimination

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age.[ Read more

Toxicity

LD50=20 mg/kg (orally in rat). Hypermetabolic state indistinguishable from thyrotoxicosis of endogenous origin. Symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood press... Read more

Adverse Effects

Contraindications

  • Route:
    • Oral
  • Regions: Canada
  • Patient Conditions:
      • Name: Untreated subclinical or overt thryrotoxicosis
      • Drugbank Id: DBCOND0107743
  • Route:
    • Oral
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute Myocardial Infarction
      • Drugbank Id: DBCOND0030399
      • Modification Of:
        • Base:
          • Name: Myocardial Infarction
          • Drugbank Id: DBCOND0027900
        • Severity:
          • Includes:
            • acute
  • Route:
    • Intravenous
    • Intramuscular
  • Dose Form:
    • Injection
  • Hypersensitivity:
    • false
  • Regions: US
  • Route:
    • Oral
  • Regions: US
  • Patient Conditions:
      • Name: Uncorrected adrenal insufficiency
      • Drugbank Id: DBCOND0107744

Food Interactions

  • Absorption increased in fasting state and decreased in malabsorption states.
  • Consistent administration in relation to meals is recommended.
  • No iron or calium carbonate within 4 hours of taking this medication.
  • Oral administration with infant soybean formula, soybean flour, cotton seed meal, walnuts, foods containing large amounts of fiber, ferrous sulfate, and antacids may decrease drug absorption.
  • Take 30-60 minutes before breakfast.

Interactions

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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
2,5-Dimethoxy-4-ethylamphetamine
The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Levothyroxine.
2,5-Dimethoxy-4-ethylthioamphetamine
The risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Levothyroxine.
3-isobutyl-1-methyl-7H-xanthine
Levothyroxine may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
4-Bromo-2,5-dimethoxyamphetamine
The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Levothyroxine.
5-fluorouridine
The therapeutic efficacy of Levothyroxine can be decreased when used in combination with 5-fluorouridine.
6-Deoxyerythronolide B
The metabolism of Levothyroxine can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanine
Levothyroxine may increase the excretion rate of 6-O-benzylguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-Deazaguanine
Levothyroxine may increase the excretion rate of 7-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
7-ethyl-10-hydroxycamptothecin
The metabolism of Levothyroxine can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
7,9-Dimethylguanine
Levothyroxine may increase the excretion rate of 7,9-Dimethylguanine which could result in a lower serum level and potentially a reduction in efficacy.
8-azaguanine
Levothyroxine may increase the excretion rate of 8-azaguanine which could result in a lower serum level and potentially a reduction in efficacy.
8-chlorotheophylline
Levothyroxine may increase the excretion rate of 8-chlorotheophylline which could result in a lower serum level and potentially a reduction in efficacy.
9-aminocamptothecin
The metabolism of Levothyroxine can be decreased when combined with 9-aminocamptothecin.
9-Deazaguanine
Levothyroxine may increase the excretion rate of 9-Deazaguanine which could result in a lower serum level and potentially a reduction in efficacy.
9-Methylguanine
Levothyroxine may increase the excretion rate of 9-Methylguanine which could result in a lower serum level and potentially a reduction in efficacy.
Abatacept
The metabolism of Levothyroxine can be increased when combined with Abatacept.
Acalabrutinib
The metabolism of Levothyroxine can be decreased when combined with Acalabrutinib.
Acebutolol
The risk or severity of adverse effects can be increased when Acebutolol is combined with Levothyroxine.
Acefylline
Levothyroxine may increase the excretion rate of Acefylline which could result in a lower serum level and potentially a reduction in efficacy.
Acetaminophen
The metabolism of Levothyroxine can be increased when combined with Acetaminophen.
14 References
  1. 1 . Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H: Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002 Apr;61(4):729-37.PubMed: 11901210
  2. 2 . Cheng SY, Leonard JL, Davis PJ: Molecular aspects of thyroid hormone actions. Endocr Rev. 2010 Apr;31(2):139-70. doi: 10.1210/er.2009-0007. Epub 2010 Jan 5.PubMed: 20051527
  3. 3 . Chon DA, Reisman T, Weinreb JE, Hershman JM, Leung AM: Concurrent Milk Ingestion Decreases Absorption of Levothyroxine. Thyroid. 2018 Apr;28(4):454-457. doi: 10.1089/thy.2017.0428. Epub 2018 Mar 28.PubMed: 29589994
  4. 4 . Tang R, Wang J, Yang L, Ding X, Zhong Y, Pan J, Yang H, Mu L, Chen X, Chen Z: Subclinical Hypothyroidism and Depression: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2019 Jun 4;10:340. doi: 10.3389/fendo.2019.00340. eCollection 2019.PubMed: 31214119
  5. 5 . Gottwald-Hostalek U, Uhl W, Wolna P, Kahaly GJ: New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. Curr Med Res Opin. 2017 Feb;33(2):169-174. doi: 10.1080/03007995.2016.1246434. Epub 2016 Oct 21.PubMed: 27718637
  6. 6 . Osmak-Tizon L, Poussier M, Cottin Y, Rochette L: Non-genomic actions of thyroid hormones: Molecular aspects. Arch Cardiovasc Dis. 2014 Apr;107(4):207-11. doi: 10.1016/j.acvd.2014.02.001. Epub 2014 Mar 26.PubMed: 24680385
  7. 7 . Klein I, Ojamaa K: Thyroid hormone and the cardiovascular system. N Engl J Med. 2001 Feb 15;344(7):501-9. doi: 10.1056/NEJM200102153440707.PubMed: 11172193
  8. 8 . Kaplan MM, Breitbart R: Conversion of thyroxine to triiodothyronine in the anterior pituitary gland and the influence of this process on thyroid status. Horm Metab Res Suppl. 1984;14:79-85.PubMed: 6595194
  9. 9 . Hammes SR, Davis PJ: Overlapping nongenomic and genomic actions of thyroid hormone and steroids. Best Pract Res Clin Endocrinol Metab. 2015 Aug;29(4):581-93. doi: 10.1016/j.beem.2015.04.001. Epub 2015 Apr 22.PubMed: 26303085
  10. 10 . Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, Sawka AM: Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014 Dec;24(12):1670-751. doi: 10.1089/thy.2014.0028.PubMed: 25266247
  11. 11 . Davis PJ, Leonard JL, Davis FB: Mechanisms of nongenomic actions of thyroid hormone. Front Neuroendocrinol. 2008 May;29(2):211-8. doi: 10.1016/j.yfrne.2007.09.003. Epub 2007 Oct 5.PubMed: 17983645
  12. 12 . Bergh JJ, Lin HY, Lansing L, Mohamed SN, Davis FB, Mousa S, Davis PJ: Integrin alphaVbeta3 contains a cell surface receptor site for thyroid hormone that is linked to activation of mitogen-activated protein kinase and induction of angiogenesis. Endocrinology. 2005 Jul;146(7):2864-71. doi: 10.1210/en.2005-0102. Epub 2005 Mar 31.PubMed: 15802494
  13. 13 . FDA Label - levothyroxine File
  14. 14 . American Association of Clinical Endocrinologists (AACE): Clinical Practice Guidelines for Hypothyroidism in Adults File