Levothyroxine

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Levothyroxine
Levothyroxine 200.svg
T4-3D-vdW.png
Identifiers
CAS number 51-48-9 YesY
PubChem 5819
ChemSpider 5614 YesY
UNII Q51BO43MG4 N
DrugBank DB00451
MeSH Thyroxine
ChEBI CHEBI:18332 YesY
ChEMBL CHEMBL1624 YesY
ATC code H03AA01
Jmol-3D images Image 1
Pharmacology
Bioavailability ~100%
Routes of
administration
Oral, intravenous
Metabolism Mainly in liver, kidneys, brain and muscles
Elimination
half-life
ca. 7 days (in hyperthyroidism 3-4 days, in hypothyroidism 9-10 days)
Excretion Through feces and urine


Prescription only

Pregnancy
category
Properties
Molecular formula C15H11I4NO4
Molar mass 776.87 g mol−1
Melting point 231 to 233 °C (448 to 451 °F; 504 to 506 K) [2]
Solubility in water Slightly soluble (0.105 mg·l-1 at 25 °C) [1]
Hazards
S-phrases S22-S24/25
Related compounds
Related compounds Triiodothyronine (tri-iodated)
Thyronine (without iodine)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 N (verify) (what is: YesY/N?)
Infobox references

Levothyroxine (INN, USAN) or L-thyroxine is a synthetic thyroid hormone that is chemically identical to thyroxine (T4), which is naturally secreted by the follicular cells of the thyroid gland. It is used to treat thyroid hormone deficiency, and occasionally to prevent the recurrence of thyroid cancer. Like its naturally secreted counterpart, levothyroxine is a chiral compound in the L-form. The related drug dextrothyroxine (D-thyroxine) was used in the past as a treatment for hypercholesterolemia (elevated cholesterol levels) but was withdrawn due to cardiac side effects.

History[edit]

Thyroxine was first isolated in pure form in 1914 at the Mayo Clinic by Edward Calvin Kendall from extracts of hog thyroid glands.[3] The hormone was synthesized in 1927 by British chemists Charles Robert Harington and George Barger.

Medical uses[edit]

Levothyroxine is typically used to treat hypothyroidism.[4] It may also be used to treat goiter via its ability to lower thyroid-stimulating hormone (TSH), a hormone that is considered goiter-inducing.[5][6] In 1992, President George H.W. Bush told television host Larry King that he had been prescribed levothyroxine as part of a treatment regimen for Graves' disease; the exchange was broadcast live to satellite dish owners tracking and recording backhaul channels.[7]

Adverse effects[edit]

Dosing, which is generally straight forward, must be controlled to achieve free T4 and free T3 levels within the normal reference range and elimination of hypothyroid and hyperthyroid symptoms. Once patients are stabilized annual or semiannual clinical evaluations and TSH monitoring are appropriate.[8] Long-term suppression of TSH values below normal values will frequently cause cardiac side-effects and contribute to decreases in bone mineral density (low TSH levels are also well known to contribute to osteoporosis).[9]

Patients prescribed too high a dose of levothyroxine may experience effects that mimic hyperthyroidism.[10] Overdose can result in heart palpitations, abdominal pain, nausea, anxiousness, confusion, agitation, insomnia, weight loss, and increased appetite.[11] Allergic reactions to the drug are characterized by symptoms such as difficulty breathing, shortness of breath, or swelling of the face and tongue. Acute overdose may cause fever, hypoglycemia, heart failure, coma and unrecognized adrenal insufficiency.

Acute massive overdose may be life-threatening; treatment should be symptomatic and supportive. Massive overdose can be associated with increased sympathetic activity and thus require treatment with beta-blockers.[10]

The effects of overdosing appear 6 hours to 11 days after ingestion.[11]

Interactions[edit]

There are foods and other substances that can interfere with absorption of thyroxine. Examples include calcium and iron supplements taken within 4 hours of levothyroxine,[12] as well as soy products within 3 hours of the medication. Other substances that reduce absorption are aluminium and magnesium containing antacids, simethicone, sucralfate, cholestyramine, colestipol, and polystyrene sulfonate. Grapefruit juice may delay the absorption of levothyroxine, but based on a study of 10 healthy people aged 20–30 (8 men, 2 women) it may not have a significant effect on bioavailability in young adults.[13] A study of eight women suggested that coffee may interfere with the intestinal absorption of levothyroxine, though at a level less than eating bran.[14] Certain other substances can cause adverse effects that may be severe. Combination of levothyroxine with ketamine may cause hypertension and tachycardia;[15] and tricyclic and tetracyclic antidepressants increase its toxicity. On the other hand lithium can cause hyperthyroidism (but most often hypothyroidism) by affecting iodine metabolism of the thyroid itself and thus inhibits synthetic levothyroxine as well.[citation needed]

Dosage[edit]

Generic levothyroxine, 25 µg oral tablet

Dosages vary according to the age groups and the individual condition of the patient, body weight and compliance to the medication and diet. Monitoring of the patient's condition and adjustment of the dosage is periodical and necessary. Levothyroxine is taken on an empty stomach approximately half an hour to an hour before meals.[10]

Common brand names[edit]

Common brand names include Eltroxin, Euthyrox, Letrox, Levaxin, L-thyroxine, Thyrax, and Thyrax Duotab in Europe; Thyrox in South Asia; Eutirox, Levoxyl, Synthroid, and Tirosint in North and South America; and Thyrin and Thyrolar in Bangladesh. There are also numerous generic versions.

See also[edit]

References[edit]

  1. ^ Levothyroxine in the ChemIDplus database
  2. ^ Harington (1926). Biochem J 20: 310. 
  3. ^ E.C. Kendall (1915). "The isolation in crystalline form of the compound containing iodin, which occurs in the thyroid: Its chemical nature and physiologic activity". J. Am. Med. Assoc. 64: 2042–2043. 
  4. ^ Vaidya B, Pearce SH. Management of hypothyroidism in adults. BMJ (Clinical research ed.). 2008;337:a801. doi:10.1136/bmj.a801. PMID 18662921.
  5. ^ Svensson J, Ericsson UB, Nilsson P, et al.. Levothyroxine treatment reduces thyroid size in children and adolescents with chronic autoimmune thyroiditis. The Journal of Clinical Endocrinology and Metabolism. 2006;91(5):1729–34. doi:10.1210/jc.2005-2400. PMID 16507633.
  6. ^ Dietlein, M.; Wegscheider, K.; Vaupel, R.; Schmidt, M.; Schicha, H. (2007). "Management of multinodular goiter in Germany (Papillon 2005): do the approaches of thyroid specialists and primary care practitioners differ?". Nuklearmedizin. Nuclear medicine 46 (3): 65–75. PMID 17549317.  edit
  7. ^ Springer, Brian (1995). Spin (Motion picture). Retrieved 11/2/2013.  (Wikipedia article: Spin)
  8. ^ Medscape, Hypothyroidism Treatment & Management - Author: Philip R Orlander, MD; Chief Editor: George T Griffing, MD more...
  9. ^ Frilling, A; Liu, C; Weber, F (2004). "Benign multinodular goiter". Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society 93 (4): 278–81. PMID 15658668.  edit
  10. ^ a b c "Synthroid (Levothyroxine Sodium) Drug Information: Uses, Side Effects, Drug Interactions and Warnings". RxList. Retrieved 2010-07-18. 
  11. ^ a b Irizarry, Lisandro. WebMd. Toxicity, Thyroid Hormone; 2010-04-23 [Retrieved 2010-10-31].
  12. ^ Ruth H. Michel, Patricia J. Neafsey, Laura Cox Dzurec. Self Medication Practices among Patients taking Levothyroxine. The Internet Journal of Advanced Nursing Practice. 2004;6.
  13. ^ Lilja JJ, Laitinen K, Neuvonen PJ. Effects of grapefruit juice on the absorption of levothyroxine. Br J Clin Pharmacol. 2005;60(3):337–41. doi:10.1111/j.1365-2125.2005.02433.x. PMID 16120075.
  14. ^ Altered Intestinal Absorption of L-Thyroxine Caused by Coffee. Thyroid. March 2008 [Retrieved 2009-05-16];18(3):293–301. doi:10.1089/thy.2007.0222. PMID 18341376.
  15. ^ Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8133–4. ISBN 978-3-85200-181-4. 

External links[edit]