LIOTHYRONINE SODIUM

Thyroid hormone drugs are natural or synthetic preparations containing tetraiodothyronine (T 4 , levothyroxine) sodium or triiodothyronine (T 3 , liothyronine) sodium or both. T 4 and T 3 are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. T 4 contains four iodine atoms and is formed by the coupling of two molecules of diiodotyrosine (DIT). T 3 contains three atoms of iodine and is formed by the coupling of one molecule of DIT with one molecule of monoiodotyrosine (MIT). Both hormones are stored in the thyroid colloid as thyroglobulin and released into the circulation. The major source of T 3 has been shown to be peripheral deiodination of T 4 . T 3 is bound less firmly than T 4 in the serum, enters peripheral tissues more readily, and binds to specific nuclear receptor(s) to initiate hormonal, metabolic effects. T 4 is the prohormone which is deiodinated to T 3 for hormone activity. Thyroid hormone preparations belong to two categories: (1) natural hormonal preparations derived from animal thyroid, and (2) synthetic preparations. Natural preparations include desiccated thyroid and thyroglobulin. Desiccated thyroid is derived from domesticated animals that are used for food by man (either beef or hog thyroid), and thyroglobulin is derived from thyroid glands of the hog. Liothyronine sodium injection (T 3 ) contains liothyronine (L-triiodothyronine or L-T 3 ), a synthetic form of a natural thyroid hormone, as the sodium salt. The structural and empirical formulas and molecular weight of liothyronine sodium are given below. In euthyroid patients, 25 mcg of liothyronine is equivalent to approximately 1 grain of desiccated thyroid or thyroglobulin and 0.1 mg of L-thyroxine. Each mL of liothyronine sodium injection (T 3 ) in amber glass vials contains, in sterile non-pyrogenic aqueous solution, liothyronine sodium equivalent to 10 mcg of liothyronine; alcohol, 6.8% by volume; anhydrous citric acid, 0.175 mg; ammonia, 2.19 mg, as ammonium hydroxide; Water for Injection, USP. C:\Documents and Settings\junem.X-GEN.000\Desktop\Lio SPL\FDA Style sheets\01.jpg

Liothyronine sodium injection (T 3 ) is indicated in the treatment of myxedema coma/precoma. Liothyronine sodium injection (T 3 ) can be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.

Adults Myxedema coma is usually precipitated in the hypothyroid patient of long standing by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency. Therapy should be directed at the correction of electrolyte disturbances, possible infection, or other intercurrent illness in addition to the administration of intravenous liothyronine (T 3 ). Simultaneous glucocorticosteroids are required. Liothyronine sodium injection (T 3 ) is for intravenous administration only. It should not be given intramuscularly or subcutaneously. Prompt administration of an adequate dose of intravenous liothyronine (T 3 ) is important in determining clinical outcome. Initial and subsequent doses of liothyronine sodium injection (T 3 ) should be based on continuous monitoring of the patient’s clinical status and response to therapy. Liothyronine sodium injection (T 3 ) should normally be administered at least four hours-and not more than 12 hours-apart. Administration of at least 65 mcg/day of intravenous liothyronine (T 3 ) in the initial days of therapy was associated with lower mortality. There is limited clinical experience with intravenous liothyronine (T 3 ) at total daily doses exceeding 100 mcg/day. No controlled clinical studies have been done with liothyronine sodium injection (T 3 ). The following dosing guidelines have been derived from data analysis of myxedema coma/precoma case reports collected by SmithKline Beecham Pharmaceuticals since 1963 and from scientific literature since 1956. An initial intravenous liothyronine sodium injection (T 3 ) dose ranging from 25 mcg to 50 mcg is recommended in the emergency treatment of myxedema coma/precoma in adults. In patients with known or suspected cardiovascular disease, an initial dose of 10 mcg to 20 mcg is suggested (see WARNINGS ). However, both the initial dose and subsequent doses should be determined on the basis of continuous monitoring of the patient’s clinical condition and response to liothyronine sodium injection (T 3 ) therapy. Normally at least four hours should be allowed between doses to adequately assess therapeutic response and no more than 12 hours should elapse between doses to avoid fluctuations in hormone levels. Caution should be exercised in adjusting the dose due to the potential of large changes to precipitate adverse cardiovascular events. Review of the myxedema case reports indicates decreased mortality in patients receiving at least 65 mcg/day in the initial days of treatment. However, there is limited clinical experience at total daily doses above 100 mcg. See PRECAUTIONS-Drug Interactions for potential interactions between thyroid hormones and digitalis and vasopressors. Pediatric Use There is limited experience with liothyronine sodium injection (T 3 ) in the pediatric population. Safety and effectiveness in pediatric patients have not been established. Switching to Oral Therapy Oral therapy should be resumed as soon as the clinical situation has been stabilized and the patient is able to take oral medication. When switching a patient to liothyronine sodium tablets from liothyronine sodium injection (T 3 ), discontinue liothyronine sodium injection (T 3 ), initiate oral therapy at a low dosage, and increase gradually according to the patient’s response. If L-thyroxine rather then liothyronine sodium is used in initiating oral therapy, the physician should bear in mind that there is a delay of several days in the onset of L-thyroxine activity and that intravenous therapy should be discontinued gradually.

Thyroid hormone preparations are generally contraindicated in patients with diagnosed but as yet uncorrected adrenal cortical insufficiency or untreated thyrotoxicosis. Thyroid hormone preparations are also generally contraindicated in patients with hypersensitivity to any of the active or extraneous constituents of these preparations; however, there is no well-documented evidence in the literature of true allergic or idiosyncratic reactions to thyroid hormone. Concomitant use of liothyronine sodium injection (T 3 ) and artificial rewarming of patients is contraindicated. (See PRECAUTIONS .)

The most frequently reported adverse events were arrhythmia (6% of patients) and tachycardia (3%). Cardiopulmonary arrest, hypotension and myocardial infarction occurred in approximately 2% of patients. The following events occurred in approximately 1% or fewer of patients: angina, congestive heart failure, fever, hypertension, phlebitis and twitching. In rare instances, allergic skin reactions have been reported with liothyronine sodium tablets.

Oral Anticoagulants: Thyroid hormones appear to increase catabolism of vitamin K-dependent clotting factors. If oral anticoagulants are also being given, compensatory increases in clotting factor synthesis are impaired. Patients stabilized on oral anticoagulants who are found to require thyroid replacement therapy should be watched very closely when thyroid is started. If a patient is truly hypothyroid, it is likely that a reduction in anticoagulant dosage will be required. No special precautions appear to be necessary when oral anticoagulant therapy is begun in a patient already stabilized on maintenance thyroid replacement therapy. Insulin or Oral Hypoglycemics: Initiating thyroid replacement therapy may cause increases in insulin or oral hypoglycemic requirements. The effects seen are poorly understood and depend upon a variety of factors such as dose and type of thyroid preparations and endocrine status of the patient. Patients receiving insulin or oral hypoglycemics should be closely watched during initiation of thyroid replacement therapy. Estrogen, Oral Contraceptives: Estrogens tend to increase serum thyroxine-binding globulin (TBG). In a patient with a nonfunctioning thyroid gland who is receiving thyroid replacement therapy, free levothyroxine may be decreased when estrogens are started thus increasing thyroid requirements. However, if the patient’s thyroid gland has sufficient function, the decreased free thyroxine will result in a compensatory increase in thyroxine output by the thyroid. Therefore, patients without a functioning thyroid gland who are on thyroid replacement therapy may need to increase their thyroid dose if estrogens or estrogen-containing oral contraceptives are given. Tricyclic Antidepressants: Use of thyroid products with imipramine and other tricyclic antidepressants may increase receptor sensitivity and enhance antidepressant activity; transient cardiac arrhythmias have been observed. Thyroid hormone activity may also be enhanced. Digitalis: Thyroid preparations may potentiate the toxic effects of digitalis. Thyroid hormonal replacement increases metabolic rate, which requires an increase in digitalis dosage. Ketamine: When administered to patients on a thyroid preparation, this parenteral anesthetic may cause hypertension and tachycardia. Use with caution and be prepared to treat hypertension, if necessary. Vasopressors: Thyroid hormones increase the adrenergic effect of catecholamines such as epinephrine and norepinephrine. Therefore, use of vasopressors in patients receiving thyroid hormone preparations may increase the risk of precipitating coronary insufficiency, especially in patients with coronary artery disease. Therefore, use caution when administering vasopressors with liothyronine (T 3 ).

Storage and Handling Store between 2°C – 8°C (36°F – 46°F). Manufactured for: XGen Pharmaceuticals DJB, Inc. Big Flats, NY 14814 Revised: May 2023 LS-AF-PI-00