Liothyronine

Pronunciation

(lye oh THYE roe neen)

U.S. Brand Names

Cytomel®; Triostat®

Synonyms

Liothyronine Sodium; Sodium L -Triiodothyronine; T3 Sodium

Generic Available

Canadian Brand Names

Cytomel®

Use

Oral: Replacement or supplemental therapy in hypothyroidism; management of nontoxic goiter; a diagnostic aid

I.V.: Treatment of myxedema coma/precoma

Pregnancy Risk Factor

Pregnancy Implications

Untreated hypothyroidism may have adverse effects on fetal growth and development, and is associated with higher rate of complications; treatment should not be discontinued during pregnancy.

Lactation

Enters breast milk (small amounts)/compatible

Contraindications

Hypersensitivity to liothyronine sodium or any component of the formulation; undocumented or uncorrected adrenal insufficiency; recent myocardial infarction or thyrotoxicosis; artificial rewarming (injection)

Warnings/Precautions

Ineffective for weight reduction; high doses may produce serious or even life-threatening toxic effects particularly when used with some anorectic drugs. Use with extreme caution in patients with angina pectoris or other cardiovascular disease (including hypertension) or coronary artery disease; use with caution in elderly patients since they may be more likely to have compromised cardiovascular function. Patients with adrenal insufficiency, myxedema, diabetes mellitus and insipidus may have symptoms exaggerated or aggravated; thyroid replacement requires periodic assessment of thyroid status. Chronic hypothyroidism predisposes patients to coronary artery disease.

Adverse Reactions

1% to 10%: Cardiovascular: Arrhythmia (6%), tachycardia (3%), cardiopulmonary arrest (2%), hypotension (2%), MI (2%)

<1%: Allergic skin reactions, angina, CHF, fever, hypertension, phlebitis, twitching

Overdosage/Toxicology

Chronic overdose may cause hyperthyroidism, weight loss, nervousness, sweating, tachycardia, insomnia, heat intolerance, menstrual irregularities, palpitations, psychosis, and fever. Acute overdose may cause fever, hypoglycemia, CHF, unrecognized adrenal insufficiency.

Reduce dose or temporarily discontinue therapy. Normal hypothalamic-pituitary-thyroid axis will return to normal in 6-8 weeks. Serum T4 levels do not correlate well with toxicity. In massive acute ingestion, reduce GI absorption and give general supportive care. Excessive adrenergic activity (tachycardia) requires propranolol 1-3 mg I.V. over 10 minutes or 80-160 mg orally/day.

Drug Interactions

Aluminum- and magnesium-containing antacids, calcium carbonate, simethicone, or sucralfate: May decrease T4 absorption; separate dose from thyroid hormones by at least 4 hours.

Antidiabetic agents (biguanides, meglitinides, sulfonylureas, thiazolidinediones, insulin): Changes in thyroid function may alter requirements of antidiabetic agent. Monitor closely at initiation of therapy, or when dose is changed or discontinued.

Cholestyramine and colestipol: Decrease T4 absorption; separate dose from thyroid hormones by at least 2 hours.

Digoxin: Digoxin levels may be reduced in hyperthyroidism; therapeutic effect may be reduced. Impact of thyroid replacement should be monitored.

Estrogens: May decrease serum free-thyroxine concentrations.

Iron: Decreases T4 absorption; separate dose from thyroid hormones by at least 4 hours

Kayexalate®: Decreases T4 absorption; separate dose from thyroid hormones by at least 4 hours

Ketamine: May cause marked hypertension and tachycardia; monitor

Theophylline, caffeine: Decreased theophylline clearance in hypothyroid patients; monitor during thyroid replacement.

Tricyclic and tetracyclic antidepressants: Therapeutic and toxic effects of thyroid hormones and the antidepressant are increased.

Warfarin (and other oral anticoagulants): The hypoprothrombinemic response to warfarin may be altered by a change in thyroid function or replacement. Replacement may dramatically increase response to warfarin. However, initiation of warfarin in a patient stabilized on a dose of thyroid hormones does not appear to require a significantly different approach.

Ethanol/Nutrition/Herb Interactions

Food: Limit intake of goitrogenic foods (asparagus, cabbage, peas, turnip greens, broccoli, spinach, Brussels sprouts, lettuce, soybeans)

Stability

Vials must be stored under refrigeration at 2°C to 8°C (36°F to 46°F). Store tablets at 15°C to 30°C (59°F to 86°F).

Mechanism of Action

Exact mechanism of action is unknown; however, it is believed the thyroid hormone exerts its many metabolic effects through control of DNA transcription and protein synthesis; involved in normal metabolism, growth, and development; promotes gluconeogenesis, increases utilization and mobilization of glycogen stores, and stimulates protein synthesis, increases basal metabolic rate

Pharmacodynamics/Kinetics

Onset of action: 2-4 hours

Peak response: 2-3 days

Absorption: Oral: Well absorbed (95% in 4 hours)

Half-life elimination: 2.5 days

Excretion: Urine

Dosage

Doses should be adjusted based on clinical response and laboratory parameters.

Children: Congenital hypothyroidism: Oral: 5 mcg/day increase by 5 mcg every 3-4 days until the desired response is achieved. Usual maintenance dose: 20 mcg/day for infants, 50 mcg/day for children 1-3 years of age, and adult dose for children >3 years.

Adults:

Hypothyroidism: Oral: 25 mcg/day increase by increments of 12.5-25 mcg/day every 1-2 weeks to a maximum of 100 mcg/day; usual maintenance dose: 25-75 mcg/day.

Patients with cardiovascular disease: Refer to Elderly dosing.

T3 suppression test: Oral: 75-100 mcg/day for 7 days; use lowest dose for elderly

Myxedema: Oral: Initial: 5 mcg/day; increase in increments of 5-10 mcg/day every 1-2 weeks. When 25 mcg/day is reached, dosage may be increased at intervals of 5-25 mcg/day every 1-2 weeks. Usual maintenance dose: 50-100 mcg/day.

Myxedema coma: I.V.: 25-50 mcg

Patients with known or suspected cardiovascular disease: 10-20 mcg

Note: Normally, at least 4 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. Oral therapy should be resumed as soon as the clinical situation has been stabilized and the patient is able to take oral medication. If levothyroxine rather than 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 levothyroxine activity and that I.V. therapy should be discontinued gradually.

Simple (nontoxic) goiter: Oral: Initial: 5 mcg/day; increase by 5-10 mcg every 1-2 weeks; after 25 mcg/day is reached, may increase dose by 12.5-25 mcg. Usual maintenance dose: 75 mcg/day

Elderly: Oral: 5 mcg/day; increase by 5 mcg/day every 2 weeks

Administration

I.V.: For I.V. use only; do not administer I.M. or SubQ

Administer doses at least 4 hours, and no more than 12 hours, apart

Resume oral therapy as soon as the clinical situation has been stabilized and the patient is able to take oral medication

When switching to tablets, discontinue the injectable, initiate oral therapy at a low dosage and increase gradually according to response

If levothyroxine is used for oral therapy, there is a delay of several days in the onset of activity; therefore, discontinue I.V. therapy gradually

Monitoring Parameters

T3, TSH, heart rate, blood pressure, renal function, clinical signs of hypo- and hyperthyroidism; TSH is the most reliable guide for evaluating adequacy of thyroid replacement dosage. TSH may be elevated during the first few months of thyroid replacement despite patients being clinically euthyroid. In cases where T4 remains low and TSH is within normal limits, an evaluation of "free" (unbound) T4 is needed to evaluate further increase in dosage.

Reference Range

Free T3, serum: 250-390 pg/dL; TSH: 0.4 and up to 10 (

80 years) mIU/L; remains normal in pregnancy

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Thyroid replacement therapy is generally for life. Take as directed, in the morning before breakfast. Do not take antacids or iron preparations within 8 hours of thyroid medication. Do not discontinue without consulting prescriber. Consult prescriber if drastically increasing or decreasing intake of goitrogenic food (eg, asparagus, cabbage, peas, turnip greens, broccoli, spinach, Brussels sprouts, lettuce, soybeans). Report chest pain, rapid heart rate, palpitations, excessive sweating or heat intolerance, excessive sweating, increased nervousness, agitation, or lethargy.

Additional Information

Equivalent doses: Thyroid USP 60 mg ~ levothyroxine 0.05-0.06 mg ~ liothyronine 0.015-0.0375 mg

50-60 mg thyroid ~ 50-60 mcg levothyroxine and 12.5-15 mcg liothyronine

A synthetic form of L -Triiodothyronine (T3) can be used in patients allergic to products derived from pork or beef.

Note: Several medications have effects on thyroid production or conversion. The impact in thyroid replacement has not been specifically evaluated, but patient response should be monitored:

Methimazole: Decreases thyroid hormone secretion, while propylthiouracil decrease thyroid hormone secretion and decreases conversion of T4 to T3.

Beta-adrenergic antagonists: Decrease conversion of T4 to T3 (dose related, propranolol 160 mg/day); patients may be clinically euthyroid.

Iodide, iodine-containing radiographic contrast agents may decrease thyroid hormone secretion; may also increase thyroid hormone secretion, especially in patients with Graves' disease.

Other agents reported to impact on thyroid production/conversion include aminoglutethimide, amiodarone, chloral hydrate, diazepam, ethionamide, interferon-alpha, interleukin-2, lithium, lovastatin (case report), glucocorticoids (dose-related), mercaptopurine, sulfonamides, thiazide diuretics, and tolbutamide.

In addition, a number of medications have been noted to cause transient depression in TSH secretion, which may complicate interpretation of monitoring tests for thyroid hormones, including corticosteroids, octreotide, and dopamine. Metoclopramide may increase TSH secretion.

Anesthesia and Critical Care Concerns/Other Considerations

Equivalent dosing: 15-37.5 mcg is equivalent to 0.05-0.06 mg levothyroxine or 60 mg thyroid USP.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No precautions with vasoconstrictor are necessary if patient is well controlled with liothyronine

Mental Health: Effects on Mental Status

May cause nervousness or insomnia

Mental Health: Effects on Psychiatric Treatment

Used to augment antidepressants

Dosage Forms

Injection, solution, as sodium (Triostat®): 10 mcg/mL (1 mL) [contains alcohol 6.8%]

Tablet, as sodium (Cytomel®): 5 mcg, 25 mcg, 50 mcg

References

Dahlberg PA, Karlsson FA, and Wide L, "Triiodothyronine Intoxication," Lancet , 1979, 2(8144):700.

Helfand M and Crapo LM, "Monitoring Therapy in Patients Taking Levothyroxine," Ann Intern Med , 1990, 113(6):450-4.

Johnson DG and Campbell S, "Hormonal and Metabolic Agents," Geriatric Pharmacology , Bressler R and Katz MD, eds, New York, NY: McGraw-Hill, 1993, 427-50.

Sanders LR, "Pituitary, Thyroid, Adrenal and Parathyroid Diseases in the Elderly," Geriatric Medicine , 1990, 475-87.

Sawin CT, Geller A, Hershman JM, et al, "The Aging Thyroid. The Use of Thyroid Hormone in Older Persons," JAMA , 1989, 261(18):2653-5.

Watts NB, "Use of a Sensitive Thyrotropin Assay for Monitoring Treatment With Levothyroxine," Arch Intern Med , 1989, 149(2):309-12.

International Brand Names

Cynomel® (BR, CR, DO, FR, GT, HN, PA, SV); Cytomel® (CA, LU, NL); Dispon® (IT); Iobolin® (BR); Liothyronin® (NO, SE); Liotironina Sodica® (CL); Liotironina Sodica L.CH.® (CL); Tertroxin® (CZ, GB, HK, NZ, TH); Thybon Henning® (DE); Thyronine® (JP); Thyrotardin inject.® (DE); Tiromel® (TR); Tiroton® (RO); Ti-Tre® (IT); Triiodothyronine® (GB, RU); Tri-Iodo-Tironina® (AR); Trijodthyronin® (AT); Trijodthyronin BC® (DE); Triyodotironina Leo® (ES); Triyotex® (DO, GT, HN, MX, SV)

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