Liothyronine

Liothyronine is a manufactured form of the thyroid hormone triiodothyronine (T3).[1] It is most commonly used to treat hypothyroidism and myxedema coma.[1] It is generally less preferred than levothyroxine.[1] It can be taken by mouth or by injection into a vein.[1]

This article is about liothyronine as a medication. For the hormone, see Triiodothyronine.
Liothyronine sodium
Clinical data
Trade namesCytomel, Tertroxin, others
AHFS/Drugs.comMonograph
MedlinePlusa682462
Pregnancy
category
  • US: A (No risk in human studies)
    Routes of
    administration    		By mouth, intravenous
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding99.7%
    Elimination half-life2.5 days
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    ChEBI
    ChEMBL
    PDB ligand
    CompTox Dashboard (EPA)
    ECHA InfoCard100.000.203
    Chemical and physical data
    FormulaC15H11I3NNaO4
    Molar mass672.96 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    Side effects may occur from excessive doses.[1] This may include weight loss, fever, headache, anxiety, trouble sleeping, arrythmias, and heart failure.[1] Use in pregnancy and breastfeeding is generally safe.[2][1] Regular blood tests are recommended to verify the appropriateness of the dose being taken.[1]

    Liothyronine was approved for medical use in 1956.[1] It is available as a generic medication.[2] A month's supply in the United Kingdom costs the NHS about GB£247 as of 2019.[2] In the United States the wholesale cost of this amount is about US$22.40.[3] In 2016 it was the 257th most prescribed medication in the United States with more than a million prescriptions.[4]

    Medical uses

    Liothyronine is a generally less preferred option to levothyroxine (T4) for people with hypothyroidism.[1] It may be used when there is an impaired conversion of T4 to T3 in peripheral tissues.[1] The dose of liothyronine for hypothyroidism is a lower amount than levothyroxine due it being a higher concentrated synthetic medication.[1] About 25 μg of liothyronine is equivalent to 100 μg of levothyroxine.[2]

    In thyroid cancer or Graves' disease, ablation therapy with radioactive iodine (131I) can be used to remove trace thyroid tissue that may remain after thyroidectomy (surgical excision of the gland). For 131I therapy to be effective, the trace thyroid tissue must be avid to iodine, which is achieved by elevating the person's TSH levels.[5] For patients taking levothyroxine, TSH may be boosted by discontinuing levothyroxine for 3–6 weeks.[5] This long period of hormone withdrawal is required because of levothyroxine's relatively long biological half-life, and may result in symptoms of hypothyroidism in the patient. The shorter half-life of liothyronine permits a withdrawal period of two weeks, which may minimize hypothyroidism symptoms. One protocol is to discontinue levothyroxine, then prescribe liothyronine while the T4 levels are falling, and finally stop the liothyronine two weeks before the radioactive iodine treatment.[5]

    Liothyronine may also be used for myxedema coma because of its quicker onset of action when compared to levothyroxine.[6] Use for the treatment of obesity is not recommended.[1]

    Depression

    Adding liothyronine to tricyclic antidepressants appears useful, especially in women.[7] An algorithm developed from the STAR*D trial recommends liothyronine as an option when people have failed two antidepressant medications.[8]

    Pregnancy

    Per the U.S. FDA, liothyronine is categorized as Pregnancy Category A.[9] Thyroid hormone is minimally transferred to the fetus or placenta, however as of October 2014, studies have not shown any adverse effects to the fetus. Hypothyroid mothers should continue to take thyroid hormone replacement therapy throughout pregnancy to avoid adverse events.[10][11]

    Nursing

    Breastmilk contains a low amount of thyroid hormone, so it is important to exercise caution when breastfeeding while taking liothyronine.[10]

    Elderly

    Older people should be started on lower doses of liothyronine.[9] Plasma T3 concentrations in this population are decreased by 25% to 40%.[10] TSH must be routinely monitored since there is a risk of coronary artery disease, hyperthyroidism and excessive bone loss from inadequate or abnormal thyroid replacement.[10]

    Contraindications

    Any person with a hypersensitivity to liothyronine sodium or any active ingredient of the formulation should not be on this medication. If there is uncorrected adrenal insufficiency or thyrotoxicosis, a different approach to therapy must be considered.[9]

    Side effects

    Liothyronine may cause a number of side effects, mostly similar to symptoms of hyperthyroidism, which include:[12]

    • weight loss
    • tremor
    • headache
    • upset stomach
    • vomiting
    • diarrhea
    • stomach cramps
    • nervousness
    • irritability
    • insomnia
    • excessive sweating
    • increased appetite
    • fever
    • changes in menstrual cycle
    • sensitivity to heat

    Boxed warning

    The package insert contains the following boxed warning, as do all thyroid hormones:[9]

    Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

    Pharmacology

    Liothyronine is the most potent form of thyroid hormone. As a salt of triiodothyronine (T3), it is chemically similar and pharmacologically equivalent to T3. As such, it acts on the body to increase the basal metabolic rate, affect protein synthesis and increase the body's sensitivity to catecholamines (such as adrenaline) by permissiveness. As monotherapy or in combination therapy with SSRIs, liothyronine may also enhance generation of new neurons in the central nervous system.[13] The thyroid hormones are essential to proper development and differentiation of all cells of the human body. These hormones also regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds.

    In comparison to levothyroxine (T4), liothyronine has a faster onset of action as well as a shorter biological half-life, which may be due to less plasma protein binding to thyroxine-binding globulin and transthyretin.

    Pricing

    The British Competition and Markets Authority launched an investigation into the alleged "excessive and unfair pricing" of liothyronine tablets in 2017. It alleged that Advanz Pharma overcharged the NHS from before 2007 to July 2017. The price of a pack increased by almost 1,600% from £4.46 before it was debranded in 2007 to £258.19 by July 2017.[14]

    References
    1. "Liothyronine Sodium Monograph for Professionals". Drugs.com. Retrieved 27 February 2019.
    2. British National Formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 757. ISBN 9780857113382.
    3. "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
    4. "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
    5. "Thyroid Cancer (Papillary and Follicular)". American Thyroid Association. Retrieved 2016-12-25.
    6. Kłubo-Gwieździńska, J; Wartofsky, L (March 2012). "Thyroid emergencies". Medical Clinics of North America. 96 (2): 385–403. doi:10.1016/j.mcna.2012.01.015. PMID 22443982.
    7. Altshuler, LL; Bauer, M; Frye, MA; Gitlin, MJ; Mintz, J; Szuba, MP; Leight, KL; Whybrow, PC (October 2001). "Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature". The American Journal of Psychiatry. 158 (10): 1617–22. doi:10.1176/appi.ajp.158.10.1617. PMID 11578993.
    8. G, Bradley; Rush, J; Trivedi, M; Wisniewski, S; Spencer, D; Fava, M (2008). "The STAR*D Study: Treating Depression in the Real World". Cleveland Clinic Journal of Medicine. 75.1: 57–66. doi:10.3949/ccjm.75.1.57.
    9. Cytomel (Liothyronine Sodium) Drug Information: Warnings and Precautions - Prescribing Information at RxList, retrieved on 29-October-2014
    10. "Liothyronine (Lexi-Drugs)". LexiComp. Retrieved 29 October 2014.
    11. Montalvo, JM; Wahner, HW; Mayberry, WE; Lum, RK (Aug 1973). "Serum triiodothyronine, total thyroxine, and thyroxine to triiodothyronine ratios in paired maternal-cord sera and at one week and one month of age". Pediatr Res. 7: 706–711. doi:10.1203/00006450-197308000-00006. PMID 4200034.
    12. MedlinePlus. "Liothyronine." Last accessed July 14, 2007.
    13. Rosenthal, Lisa J.; Goldner, Whitney S.; O’Reardon, John P. (October 2011). "T3 augmentation in major depressive disorder: safety considerations". Am. J. Psychiatry. 168 (10): 1035–1040. doi:10.1176/appi.ajp.2011.10030402. PMID 21969047.
    14. "CMA investigates 1,600% price increase of liothyronine over eight-year period". Pharmaceutical Journal. 31 January 2019. Retrieved 17 March 2019.
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