2174 Thyroid and Antithyroid Drugs with methodological limitations. However, a controlled trial of In myxoedema coma liothyronine sodium may be liothyronine with paroxetine could not confirm any advantage of given intravenously in a dose of 5 to 20 micrograms by 3 O additive therapy. slow intravenous injection, repeated as necessary, usu- 1. Aronson R, et al. Triiodothyronine augmentation in the treat- HO I ally at intervals of 12 hours; the minimum interval be- ment of refractory depression: a meta-analysis. Arch Gen Psychi- OH atry 1996; 53: 842–8. tween doses is 4 hours. An alternative regimen advo- 2. Altshuler LL, et al. Does thyroid supplementation accelerate tri- NH2 cates an initial dose of 50 micrograms intravenously cyclic antidepressant response? A review and meta-analysis of I O the literature. Am J Psychiatry 2001; 158: 1617–22. followed by further injections of 25 micrograms every 3. Appelhof BC, et al. Triiodothyronine addition to paroxetine in I 8 hours until improvement occurs; the dosage may the treatment of major depressive disorder. J Clin Endocrinol then be reduced to 25 micrograms intravenously twice Metab 2004; 89: 6271–6. (liothyronine) daily. Obesity. Thyroid drugs have been tried in the treatment of obes- Liothyronine has also been given in the diagnosis of ity (p.2149) in euthyroid patients, but they produce only tempo- NOTE. The abbreviation T3 is often used for endogenous tri-io- hyperthyroidism in adults. Failure to suppress the up- rary weight loss, mainly of lean body-mass, and can produce se- dothyronine in medical and biochemical reports. Liotrix is USAN rious adverse effects, especially cardiac complications.1 for a mixture of liothyronine sodium with levothyroxine sodium. take of radio-iodine after several days of receiving lio- Hypothyroidism has also been reported2 when these drugs were Pharmacopoeias. In Eur. (see p.vii), Jpn, and US. thyronine sodium suggests a diagnosis of hyperthy- withdrawn from previously euthyroid patients being treated for Ph. Eur. 6.2 (Liothyronine Sodium). A white or almost white or roidism. simple obesity. Levothyroxine appears to have been abused by slightly coloured powder. Practically insoluble in water; slightly Liothyronine hydrochloride has also been used. some athletes to promote weight loss.3 soluble in alcohol. It dissolves in dilute solutions of alkali hy- 1. Rivlin RS. Therapy of obesity with hormones. N Engl J Med droxides. Store at 2° to 8° in airtight containers. Protect from Preparations 1975; 292: 26–9. light. BP 2008: Liothyronine Tablets; 2. Dornhorst A, et al. Possible iatrogenic hypothyroidism. Lancet USP 31 (Liothyronine Sodium). A light tan, odourless, crystal- USP 31: Liothyronine Sodium Tablets; Liotrix Tablets. 1981; i: 52. line powder. Very slightly soluble in water; slightly soluble in al- Proprietary Preparations (details are given in Part 3) 3. MacAuley D. Drugs in sport. BMJ 1996; 313: 211–15. cohol; practically insoluble in most other organic solvents. Store Austral.: Te r t r ox i n ; Braz.: Cynomel†; Canad.: Cytomel; Cz.: Tertroxin†; in airtight containers. Fr.: Cynomel; Ger.: Thybon; Thyrotardin N; Gr.: Cynomel†; T-3; Ital.: Dis- Urticaria. There is some suggestion that chronic urticaria pon†; Ti-Tre; Mex.: Cynomel; Liotrex; Triyotex; Neth.: Cytomel; NZ: Ter- (p.1584) may be associated with thyroid autoimmunity and that troxin; Port.: Neo-Tiroimade; S.Afr.: Ter troxin; Thai.: Tertroxin†; Turk.: treatment with thyroid hormones may result in clinical remis- Adverse Effects, Treatment, and Precau- Tiromel; UK: Tertroxin†; Triiodothyronine Injection; USA: Cytomel; Trio- sion.1 In one study, a nine-year-old boy was successfully treated tions stat; Venez.: Te r t r ox i n† . for chronic urticaria with levothyroxine therapy at doses of 50 to As for Levothyroxine Sodium, p.2171. Multi-ingredient: Arg.: Eutroid; Levotrin; Tresite F; Austria: Combithy- 2 rex; Novothyral; Prothyrid; Belg.: Novothyral; Braz.: Tyroplus†; Chile: 100 micrograms daily. The authors advised screening for thy- Novothyral; Cz.: Novothyral†; Thyreotom; Fr.: Euthyral; Ger.: NeyNormin roid function and anti-thyroid microsomal antibodies in cases of Interactions N (Revitorgan-Dilutionen N Nr 65)†; NeyTumorin N (Revitorgan-Dilutio- chronic urticaria as these patients may benefit from thyroid hor- nen N Nr 66)†; Novothyral; Prothyrid; Thyreotom†; Gr.: Dithyron; Ital.: mone therapy. A small investigative study concluded that treat- As for Levothyroxine Sodium, p.2172. Tiroide Amsa; Mex.: Cynoplus; Novotiral; Proloid S†; Redotex; Pol.: Novothyral; Rus.: Novothyral (Новотирал); Thyreocomb (Тиреокомб); ment with levothyroxine sodium (in hypothyroid patients) or Thyreotom (Тиреотом); S.Afr.: Diotroxin; Switz.: Novothyral; Turk.: Biti- antithyroid drugs (in patients with Graves’ disease) is of benefit Pharmacokinetics ron; USA: Thyrolar. in patients with severe chronic urticaria associated with thyroid Liothyronine is readily and almost completely ab- autoimmunity.3 sorbed from the gastrointestinal tract. Once in the cir- 1. Rumbyrt JS, et al. Resolution of chronic urticaria in patients with culation, liothyronine binds principally to thyroxine- thyroid autoimmunity. J Allergy Clin Immunol 1995; 96: 901–5. binding globulin (TBG), although less strongly than Potassium Perchlorate 2. Dreyfus DH, et al. Steroid-resistant chronic urticaria associated with anti-thyroid microsomal antibodies in a nine-year-old boy. levothyroxine; some is also bound to thyroxine-bind- Chloristan draselný; Kalii perchloras; Kalio perchloratas; Ka- J Pediatr 1996; 128: 576–8. ing pre-albumin (TBPA) or to albumin. Liothyronine liumperkloraatti; Kaliumperklorat; Kálium-perklorát; Perclorato 3. Gaig P, et al. Successful treatment of chronic idiopathic urticaria has a plasma half-life in euthyroidism of about 1 to 2 potásico; Potassium, perchlorate de. associated with thyroid autoimmunity J Investig Allergol Clin KClO = 138.5. days; the half-life is prolonged in hypothyroidism and 4 Immunol 2000; 10: 342–5. CAS — 7778-74-7. reduced in hyperthyroidism. Preparations ATC — H03BC01. Liothyronine is metabolised by deiodination to inac- ATC Vet — QH03BC01. BP 2008: Levothyroxine Tablets; USP 31: Levothyroxine Sodium Tablets; Liotrix Tablets. tive di-iodothyronine and mono-iodothyronine. Iodine released by deiodination is largely reused within the Proprietary Preparations (details are given in Part 3) thyroid cells. Further metabolites result from deamina- K+ Arg.: Euthyrox; Juno†; T4; Austral.: Eutroxsig; Oroxine; Austria: Euthyrox; O- Neothyron; Thyrex; Belg.: Elthyrone; Euthyrox; Thyrax; Braz.: Euthyrox; tion and decarboxylation to tiratricol (triac). Puran T4; Synthroid; Tetroid; Tiroidin; Canad.: Eltroxin; Euthyrox; Syn- O Cl O throid; Chile: Esaldox; Eutirox; Cz.: Eltroxin; Euthyrox; Letrox; Thyrax†; Uses and Administration Denm.: Eltroxin; Fr.: Levothyrox; Ger.: Berlthyrox; Eferox; Euthyrox; L- O Thyrox; Lixin; Thevier; Gr.: Levothroid; T-4; Thyro-4; Thyrohormone; Liothyronine is a thyroid hormone (see p.2165). It is Hong Kong: Eltroxin; Hung.: Euthyrox; Letrox; India: Eltroxin; Indon.: Euthyrox; Thyrax; Irl.: Eltroxin; Israel: Eltroxin; Ital.: Eutirox; Tiracrin; Ti- used in the treatment of hypothyroidism (p.2167), and Pharmacopoeias. In Eur. (see p.vii) and US. rosint; Jpn: Thyradin-S; Malaysia: Oroxine; Mex.: Abutiroi; Cynocuatro; is believed to be more active than levothyroxine Ph. Eur. 6.2 (Potassium Perchlorate). A white or almost white Daltroid†; Eutirox; Sintrocid†; Tiroidine; Neth.: Eltroxin; Euthyrox; Thyrax; Norw.: Levaxin; NZ: Eltroxin; Philipp.: Eltroxin; Euthyrox; Thyrax; Thyro- (p.2173). The onset of action of liothyronine is rapid, crystalline powder or colourless crystals. Sparingly soluble in hex; Pol.: Eferox; Eltroxin; Euthyrox; Letrox; Port.: Eutirox; Letequatro; developing within a few hours, and therefore it tends to water; practically insoluble in alcohol. Letter; Thyrax; Rus.: Bagothyrox (Баготирокс); Euthyrox (Эутирокс); be used in circumstances where this, and its short dura- USP 31 (Potassium Perchlorate). pH of a 0.1M solution in water S.Afr.: Eltroxin; Singapore: Eltroxin; Euthyrox; Oroxine; Spain: Dexnon; is between 5.0 and 6.5. Eutirox; Levothroid; Swed.: Euthyrox; Levaxin; Switz.: Eltroxine; Euthyrox; tion of action, are useful, particularly in hypothyroid Thai.: Elthyro; Eltroxin; Euthyrox; Pondtroxin; Thyrosit; Turk.: Levotiron; Te fo r ; UK: Eltroxin; Evotrox; USA: Levothroid; Levoxyl; Novothyrox; Syn- (myxoedema) coma. Sodium Perchlorate throid; Unithroid; Venez.: Euthyrox; Thyrax. With regular dosing the peak therapeutic effect is usu- Perclorato sódico; Sodu nadchloran. Multi-ingredient: Arg.: Eutroid; Levotrin; Austria: Combithyrex; Jodthy- ally achieved after 3 days; on withdrawal its effects rox; Novothyral; Prothyrid; Belg.: Novothyral; Braz.: Tyroplus†; Chile: NaClO4 = 122.4. Novothyral; Cz.: Jodthyrox; Novothyral†; Thyreotom; Fr.: Euthyral; Ger.: may persist for 1 to 3 days. CAS — 7601-89-0 (anhydrous sodium perchlorate); 7791- Eferox Jod; Jodthyrox; L-Thyrox Jod; Novothyral; Prothyrid; Thyreocomb 07-3 (sodium perchlorate monohydrate). N†; Thyreotom†; Thyronajod; Gr.: Dithyron; Ital.: Dermocinetic; Somato- The dose of liothyronine should be individualised on line; Tiroide Amsa; Mex.: Cynoplus; Novotiral; Proloid S†; Pol.: Jodthyrox; the basis of clinical response and biochemical tests and Novothyral; Rus.: Jodthyrox (Йодтирокс); Novothyral (Новотирал); Thy- should be monitored regularly. Although liothyronine Na+ reocomb (Тиреокомб); Thyreotom (Тиреотом);