VA Class:HS851

ATC Class:H03AA02

AHFS Class:

• Thyroid Agents 68:36.04

Generic Name(s):

• Liothyronine Sodium

Liothyronine sodium, the sodium salt of the l-isomer of 3,3',5-triiodothyronine, is a thyroid agent.

Liothyronine sodium may be used for replacement or substitution of diminished or absent thyroid function resulting from primary causes including functional deficiency, primary atrophy, or partial or complete absence of the gland or the effects of surgery, radiation, or antithyroid agents; however, levothyroxine sodium is generally preferred for long-term therapy in these conditions. Liothyronine sodium also may be used for replacement or supplemental therapy in patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism. Therapy must be maintained continuously to control the symptoms of hypothyroidism. Because liothyronine sodium has a rapid onset and short duration of action, some clinicians prefer its use to levothyroxine sodium when a rapid effect or rapidly reversible effect is desired (e.g., diagnostic procedures requiring short-term thyrotropin suppression, myxedema coma); however, the fact that liothyronine produces wide swings in serum triiodothyronine concentrations and the possibility of more pronounced adverse cardiovascular effects generally make the drug unsatisfactory for long-term use. Liothyronine sodium may be useful when absorption of levothyroxine sodium is questionable or impairment of peripheral conversion of thyroxine to triiodothyronine is suspected.

Liothyronine sodium may also be used therapeutically in patients with simple (nontoxic) goiter to reduce the size of the goiter.

Liothyronine sodium is used IV in the treatment of myxedema coma or precoma. Simultaneous administration of corticosteroids is required. Myxedema coma should be considered a medical emergency, and therapy should be directed at the correction of electrolyte disturbances, possible infection, or other intercurrent illness in addition to the administration of IV liothyronine sodium.

Liothyronine sodium is used principally in the T₃ suppression test to differentiate suspected hyperthyroidism from euthyroidism in patients with I 131 thyroid uptake values in the borderline-high range.

Administration

Liothyronine sodium is administered orally. The drug also is administered by IV injection in the treatment of myxedema coma or precoma. The manufacturer states that liothyronine sodium injection should not be administered IM or subcutaneously.

Dosage

Dosage of liothyronine sodium is expressed in terms of liothyronine. Dosage of liothyronine must be carefully adjusted according to individual requirements and response. The age and general physical condition of the patient and the severity and duration of hypothyroid symptoms determine the initial dosage and the rate at which dosage may be increased to the eventual maintenance dosage. Dosage should be initiated at a lower level in geriatric patients; in patients with long-standing disease, other endocrinopathies, or functional or ECG evidence of cardiovascular disease; and in patients with severe hypothyroidism. Adjustment of thyroid replacement therapy should be determined mainly by the patient's clinical response and confirmed by appropriate laboratory tests.

Prompt administration of an adequate dose of IV liothyronine sodium is important in determining clinical outcome of myxedema coma. Initial and subsequent doses of liothyronine sodium should be based on continuous monitoring of the patient's clinical status and response to therapy. Myxedematous patients are very sensitive to the effects of thyroid hormones; therefore, dosage in such patients should be initiated at a low level and increased gradually since acute changes may precipitate adverse cardiovascular events.

For the management of mild hypothyroidism in adults, the usual initial oral dosage of liothyronine is 25 mcg daily given as a single dose; dosage is increased by increments of 12.5 or 25 mcg daily at intervals of 1-2 weeks until the desired response is obtained. The usual maintenance dosage is 25-75 mcg daily; some patients may require higher or lower dosages. For the management of severe hypothyroidism in adults, the usual initial oral dosage is 5 mcg daily given as a single dose; dosage is increased by increments of 5-10 mcg daily at intervals of 1-2 weeks until the desired response is obtained. The usual maintenance dosage is 50-100 mcg daily. For geriatric patients with hypothyroidism, the usual initial oral dosage of liothyronine is 5 mcg daily given as a single dose; dosage is increased by increments of 5 mcg daily at intervals of 1-2 weeks until the desired response is obtained.

In infants and children, it is essential to achieve rapid and complete thyroid replacement because of the critical importance of thyroid hormone in sustaining growth and maturation. In general, despite the smaller body size, the dosage (on a weight basis) required to sustain a full rate of growth, development, and general thriving is higher in children than in adults. Although levothyroxine sodium is considered the drug of choice for the treatment of congenital hypothyroidism (cretinism), liothyronine has been used. The initial oral dosage of liothyronine recommended by the manufacturer for the treatment of congenital hypothyroidism is 5 mcg daily given as a single dose; dosage is increased by increments of 5 mcg daily at intervals of 3-4 days until the desired response is obtained. For additional information on the use of thyroid agents in the treatment of congenital hypothyroidism, see Cautions: Pediatric Precautions, in the Thyroid Agents General Statement 68:36.04.

For the management of simple (nontoxic) goiter in adults, the usual initial oral dosage of liothyronine is 5 mcg daily; dosage is increased by increments of 5-10 mcg daily at intervals of 1-2 weeks until a dosage of 25 mcg daily is reached. Thereafter, dosage may be increased by increments of 12.5 or 25 mcg daily at intervals of 1-2 weeks until the desired response is obtained. The usual maintenance dosage is 75 mcg daily.

When a patient is transferred from another thyroid preparation to liothyronine, the other thyroid preparation should be discontinued and liothyronine therapy initiated at a low dosage. Liothyronine dosage may be increased in small increments after residual effects of the previous thyroid preparation have subsided. When a patient is transferred from liothyronine to another thyroid preparation, it must be kept in mind that the onset and dissipation of effects of liothyronine are relatively rapid, and, to avoid relapse, it is necessary to start therapy with the replacement thyroid preparation several days before complete withdrawal of liothyronine.

Although levothyroxine sodium is generally considered the drug of choice in the treatment of myxedema coma, some clinicians prefer liothyronine because of its rapid onset of action. Liothyronine has been given orally via a nasogastric tube, but the IV route of administration is preferred. The usual initial adult IV dose of liothyronine recommended by the manufacturer for the emergency treatment of myxedema coma or precoma is 25-50 mcg. In patients with known or suspected cardiovascular disease, the manufacturer suggests an initial dose of 10-20 mcg of liothyronine. The manufacturer states that additional doses of liothyronine should be administered at least 4 hours after the initial dose to allow for adequate assessment of therapeutic response, but no more than 12 hours should elapse between doses to avoid fluctuations in hormone levels. However, both the initial and subsequent doses of the drug should be determined based on continuous monitoring of the patient's clinical condition and response to liothyronine sodium therapy. Administration of at least 65 mcg daily of IV liothyronine in the initial days of therapy reportedly has been associated with lower mortality. However, clinical experience with liothyronine dosages exceeding 100 mcg daily is limited. Oral therapy with thyroid hormones should be resumed as soon as the patient's condition stabilizes and the drug can be given orally. Oral therapy with liothyronine sodium should be initiated at a low dosage following discontinuance of the IV drug, and dosage should be increased gradually according to the patient's response. If levothyroxine sodium rather than liothyronine sodium is used in initiating oral therapy, the clinician should consider the delay in onset of activity of levothyroxine sodium and IV liothyronine sodium should be discontinued gradually.

When used in the T₃ suppression test to differentiate suspected hyperthyroidism from euthyroidism, liothyronine is given in a dosage of 75-100 mcg daily for 7 days. Radioactive I 131 uptake test is performed before and after administration of the 7-day course of liothyronine. In patients with hyperthyroidism, the radioactive iodine thyroid uptake will not be substantially affected, while in the euthyroid patient, it will decrease to less than 20% of the baseline value.

For further information on chemistry, pharmacology, pharmacokinetics, uses, toxicity, cautions, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of liothyronine sodium, see the Thyroid Agents General Statement 68:36.04.

Liothyronine sodium shares the toxic potentials of other thyroid agents, and the usual precautions of thyroid agent therapy should be observed. (See Toxicity and Cautions in the Thyroid Agents General Statement 68:36.04). Adverse reactions to liothyronine sodium result from overdosage and are manifested principally as signs and symptoms of hyperthyroidism.

The manufacturer states that there is limited clinical experience with liothyronine sodium injection in children and that safety and efficacy of this preparation have not been established in children.

Pharmacology

The principal pharmacologic effect of exogenous thyroid hormones is to increase the metabolic rate of body tissues. Thyroid hormones are also involved in the regulation of cell growth and differentiation. Although the precise mechanism of action by which thyroid hormones affect metabolism and cellular growth and differentiation is not clearly established, it is known that these physiologic effects are mediated at the cellular level, principally via triiodothyronine; a major portion of triiodothyronine is derived from thyroxine by deiodination in peripheral tissues.

Pharmacokinetics

Liothyronine sodium is almost completely absorbed from the GI tract (about 95%) following oral administration. Because triiodothyronine is not highly or firmly protein bound, liothyronine has a more rapid onset of pharmacologic action and a shorter duration of action than levothyroxine. The usual plasma half-lives of triiodothyronine and thyroxine are approximately 1-2 days and 6-7 days, respectively. The plasma half-lives of thyroxine and triiodothyronine are decreased in patients with hyperthyroidism and increased in those with hypothyroidism.

Following a single IV dose of liothyronine sodium, a detectable metabolic response occurs within as little as 2-4 hours, with a maximum therapeutic response within 2 days.

Chemistry and Stability

Chemistry

Liothyronine sodium is the sodium salt of the l-isomer of 3,3',5-triiodothyronine. Liothyronine sodium is prepared synthetically. Structurally, liothyronine sodium differs from levothyroxine sodium only in the absence of an iodine atom in the 5' position. Each 25 mcg of liothyronine sodium is approximately clinically equivalent to 60-65 mg of thyroid or thyroglobulin or 100 mcg or less of levothyroxine sodium.

Liothyronine sodium occurs as a light tan, odorless, crystalline powder and is very slightly soluble in water and slightly soluble in alcohol.

Stability

Commercially available liothyronine sodium tablets should be stored in tight containers at a temperature less than 40°C, preferably between 15-30°C. Commercially available liothyronine sodium injection should be stored at 2-8°C.