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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(lye oh THYE roe neen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Oral: Replacement or supplemental therapy in hypothyroidism; management of nontoxic goiter; a diagnostic aid
I.V.: Treatment of myxedema coma/precoma
Use: Unlabeled/Investigational
Management of hemodynamically unstable potential organ donors increasing the quantity of organs available for transplantation
Pregnancy Risk Factor
A
Pregnancy Considerations
Adverse events have not been observed following use in pregnant women; therefore, the manufacturer classifies liothyronine as pregnancy category A.Endogenous thyroid hormones minimally cross the placenta. Liothyronine has not been found to increase the risk of teratogenic or adverse effects following maternal use during pregnancy. Maternal hypothyroidism, however, can be associated with adverse effects in the fetus and infant. Adverse events can be decreased by maintaining maternal euthyroidism during pregnancy. Levothyroxine is the treatment of choice for maternal hypothyroidism to decrease the risk of infertility and adverse events.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Endogenous thyroid hormones are minimally found in breast milk. Liothyronine was not found to cause adverse events to the infant during breast-feeding.
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
Boxed warnings:
• Weight reduction (unlabeled use): See “Other warnings/precautions” below.
Disease-related concerns:
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency; symptoms may be exaggerated or aggravated.
• Cardiovascular disease: Use with caution and reduce dosage in patients with angina pectoris or other cardiovascular disease; chronic hypothyroidism predisposes patients to coronary artery disease.
• Diabetes: Use with caution in patients with diabetes mellitus and insipidus; symptoms may be exaggerated or aggravated.
• Myxedema: Use with caution in patients with myxedema; symptoms may be exaggerated or aggravated.
Special populations:
• Elderly: Use with caution in elderly patients; they may be more likely to have compromised cardiovascular function.
Other warnings/precautions:
• Monitoring: Thyroid replacement requires periodic assessment of thyroid status.
• Weight reduction (unlabeled use): [U.S. Boxed Warning]: Thyroid supplements are ineffective and potentially toxic for weight reduction.
High doses may produce serious or even life-threatening toxic effects particularly when used with some anorectic drugs.
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
Metabolism/Transport Effects
None known.
Drug Interactions
Bile Acid Sequestrants: May decrease the absorption of Thyroid Products. Risk C: Monitor therapy
Calcium Polystyrene Sulfonate: May decrease the serum concentration of Thyroid Products. Management: To minimize risk of interaction, separate dosing of oral calcium polystyrene sulfonate and thyroid products (eg, levothyroxine) or administer calcium polystyrene sulfonate rectally. Monitor for signs/symptoms of hypothyroidism with concomitant use (oral). Risk D: Consider therapy modification
Calcium Salts: May diminish the therapeutic effect of Thyroid Products. Management: Separate the doses of the thyroid product and the oral calcium supplement by at least 4 hours. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
Estrogen Derivatives: May diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least two hours before or after lanthanum. Risk D: Consider therapy modification
Phenytoin: May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites. Risk C: Monitor therapy
Rifampin: May decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
Sodium Iodide I131: Thyroid Products may diminish the therapeutic effect of Sodium Iodide I131. Risk X: Avoid combination
Sodium Polystyrene Sulfonate: May decrease the serum concentration of Thyroid Products. Management: To minimize risk of interaction, separate dosing of oral sodium polystyrene sulfonate and thyroid products (e.g., levothyroxine) or administer sodium polystyrene sulfonate rectally. Monitor for signs/symptoms of hypothyroidism with concomitant use (oral). Risk D: Consider therapy modification
Theophylline Derivatives: Thyroid Products may increase the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Thyroid Products may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Storage
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: ~3 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: Oral
When switching to tablets, discontinue the injectable, initiate oral therapy at a low dosage, and increase gradually according to response.
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. 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
Test Interactions
Many drugs may have effects on thyroid function tests (see Additional Information or Pharmacotherapy Pearls). Pregnancy, infectious hepatitis, and acute intermittent porphyria may increase TBG concentrations; nephrosis, severe hypoproteinemia, severe liver disease, and acromegaly may decrease TBG concentrations.
Patient Education
Thyroid replacement therapy is generally for life. Take in the morning before breakfast. Do not take antacids or iron preparations within 8 hours of thyroid medication. Report chest pain, rapid heart rate, palpitations, excessive sweating or heat intolerance, excessive sweating, increased nervousness, agitation, or lethargy.
Geriatric Considerations
Elderly do not have a change in serum thyroxine associated with aging; however, plasma T3 concentrations are decreased 25% to 40% in the elderly. There is not a compensatory rise in thyrotropin suggesting that lower T3 is not reacted upon as a deficiency by the pituitary. This indicates a slightly lower than normal dosage of thyroid hormone replacement is usually sufficient in elderly patients than in younger adult patients. TSH must be monitored since insufficient thyroid replacement (elevated TSH) is a risk for coronary artery disease and excessive replacement (low TSH) may cause signs of hyperthyroidism and excessive bone loss.
Additional Information
Equivalent doses: The following statement on relative potency of thyroid products is included in a joint statement by American Thyroid Association (ATA), American Association of Clinical Endocrinologists (AACE) and The Endocrine Society (TES): For purposes of conversion, levothyroxine sodium (T4) 100 mcg is usually considered equivalent to desiccated thyroid 60 mg, thyroglobulin 60 mg, or liothyronine sodium (T3) 25 mcg. However, these are rough guidelines only and do not obviate the careful re-evaluation of a patient when switching thyroid hormone preparations, including a change from one brand of levothyroxine to another. Joint position statement is available at http://www.thyroid.org/professionals/advocacy/04_12_08_thyroxine.html.
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
Clinical Pearls/Comments: Equivalent doses: The following statement on relative potency of thyroid products is included in a joint statement by American Thyroid Association (ATA), American Association of Clinical Endocrinologists (AACE) and The Endocrine Society (TES): For purposes of conversion, levothyroxine sodium (T4) 100 mcg is usually considered equivalent to desiccated thyroid 60 mg, thyroglobulin 60 mg, or liothyronine sodium (T3) 25 mcg. However, these are rough guidelines only and do not obviate the careful re-evaluation of a patient when switching thyroid hormone preparations, including a change from one brand of levothyroxine to another. Joint position statement is available at http://www.thyroid.org/professionals/advocacy/04_12_08_thyroxine.html.
Evidence-Based Information: Cadaveric organ donation: Hemodynamically unstable donors: Hormonal resuscitation: Intravenous liothyronine (4 mcg bolus followed by 3 mcg/hour) given concomitantly with a continuous infusion of insulin (1 unit/hour minimum; titrated to BG 120-180 mg/dL), 15 mg/kg of methylprednisolone, and vasopressin (1 unit bolus followed by 0.5-4 units/hour; titrate to SVR 800-1200 dyne·s/cm5) has been successfully used in hemodynamically unstable brain-dead donors to increase the quantity and quality of organs available for transplantation (Rosendale, 2003; Rosengard, 2002). Of note, stability of further diluted injectable levothyroxine (after reconstitution) and liothyronine solutions has not been adequately studied.
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
Nursing: Physical Assessment/Monitoring
Monitor for hyper-/hypothyroidism regularly during therapy.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution: 10 mcg/mL (1 mL)
Triostat®: 10 mcg/mL (1 mL) [contains ethanol 6.8%]
Tablet, oral: 5 mcg, 25 mcg, 50 mcg
Cytomel®: 5 mcg
Cytomel®: 25 mcg, 50 mcg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Cytomel)
5 mcg (100): $97.99
25 mcg (100): $125.98
50 mcg (100): $192.98
Tablets (Liothyronine Sodium)
5 mcg (100): $75.99
25 mcg (100): $95.99
50 mcg (100): $153.98
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.
Rosendale JD, Kauffman HM, McBride MA, et al, “Aggressive Pharmacologic Donor Management Results in More Transplanted Organs,” Transplantation, 2003, 75(4):482-7.
Rosengard BR, Feng S, Alfrey EJ, et al, “Report of the Crystal City Meeting to Maximize the Use of Organs Recovered From the Cadaver Donor,” Am J Transplant, 2002, 2(8):701-11.
Salim A, Martin M, Brown C, et al, “Using Thyroid Hormone in Brain-Dead Donors to Maximize the Number of Organs Available for Transplantation,” Clin Transplant, 2007, 21(3):405-9.
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
Lexi-Comp.com
Last full review/revision November 2011
Content last modified November 2011
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