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Liothyronine

Pronunciation

Pronunciation

(lye oh THYE roe neen)

Index Terms

  • Liothyronine Sodium
  • Sodium L-Triiodothyronine
  • T3 Sodium (error-prone abbreviation)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Triostat: 10 mcg/mL (1 mL) [contains alcohol, usp]

Generic: 10 mcg/mL (1 mL)

Tablet, Oral:

Cytomel: 5 mcg

Cytomel: 25 mcg, 50 mcg [scored]

Generic: 5 mcg, 25 mcg, 50 mcg

Brand Names: U.S.

  • Cytomel
  • Triostat

Pharmacologic Category

  • Thyroid Product

Pharmacology

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

Absorption

Oral: Well absorbed (95% in 4 hours)

Excretion

Urine

Onset of Action

~3 hours

Half-Life Elimination

0.75 days (Brent 2011)

Use: Labeled Indications

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

IV: Treatment of myxedema coma/precoma

Use: Unlabeled

Management of hemodynamically unstable potential organ donors increasing the quantity of organs available for transplantation

Contraindications

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

Dosing: Adult

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

Patients with cardiovascular disease: Refer to geriatric dosing.

Suppression test: (T3): Oral: 75 to 100 mcg/day for 7 days; use lowest dose for elderly

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

Myxedema coma: IV: 25 to 50 mcg

Patients with known or suspected cardiovascular disease: 10 to 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 prescriber should bear in mind that there is a delay of several days in the onset of levothyroxine activity and that IV therapy should be discontinued gradually.

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

Antidepressant augmentation (off-label use): Oral: Initial: 25 mcg/day; may be increased to 50 mcg/day after ~1 week based on response and tolerability (APA 2010). Dose ranges of 20 to 62.5 mcg/day have been studied in clinical trials (Altshuler 2001; Aronson, 1996; Nierenberg 2006). Note: The duration of treatment has not been well studied (APA 2010; Cooper-Kazaz 2008). If the patient has a history of multiple episodes or significant treatment resistance, long-term maintenance treatment is reasonable if there are no symptoms of hyperthyroidism and no known cardiac disease (Rosenthal 2011).

Cadaveric organ recovery (hormonal resuscitation) (off-label use): IV: Initial: 4 mcg bolus followed by a continuous infusion of 3 mcg/hour administered to the brain-dead donor who is hemodynamically unstable requiring significant vasopressor support; give concomitantly with vasopressin, methylprednisolone, and continuous regular insulin infusion (maintain blood glucose 120 to 180 mg/dL) (Rosendale 2003a; Rosendale 2003b; Rosengard 2002; Zaroff 2002).

Dosing: Geriatric

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

Dosing: Pediatric

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

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling.

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling.

Administration

IV: For IV use only; do not administer IM or SubQ

Intermittent IV administration: Administer at a rate of 10 mcg/minute.

Continuous IV infusion: Cadaveric organ recovery (hormonal resuscitation) (off-label use): After IV bolus administration, may administer as a continuous infusion (Rosengard 2002; Zaroff 2002).

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).

Drug Interactions

Bile Acid Sequestrants: May decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least 4 h prior to colesevelam, and at least 1 h before or 4-6 h after cholestyramine. Specific recommendations for colestipol are not available. Monitor for decreased concentrations/effects of the thyroid product. Consider therapy modification

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). 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. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Thyroid Products. Monitor therapy

Ciprofloxacin (Systemic): May decrease the serum concentration of Thyroid Products. Monitor therapy

Estrogen Derivatives: May diminish the therapeutic effect of Thyroid Products. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites. Monitor therapy

Lanthanum: May decrease the serum concentration of Thyroid Products. Management: Administer oral thyroid products at least two hours before or after lanthanum. Consider therapy modification

Phenytoin: May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites. Monitor therapy

Piracetam: May enhance the adverse/toxic effect of Thyroid Products. Specifically, symptoms including confusion, irritability, and sleep disorder have been described during concomitant use. Monitor therapy

RifAMPin: May decrease the serum concentration of Thyroid Products. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Monitor therapy

Sodium Iodide I131: Thyroid Products may diminish the therapeutic effect of Sodium Iodide I131. 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). Consider therapy modification

Theophylline Derivatives: Thyroid Products may increase the metabolism of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

Tricyclic Antidepressants: Thyroid Products may enhance the arrhythmogenic effect of Tricyclic Antidepressants. Thyroid Products may enhance the stimulatory effect of Tricyclic Antidepressants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Thyroid Products may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

T4-binding globulin (TBG): Factors that alter binding in serum (ATA/AACE [Garber 2012]):

Note: T4 is ~99.97% protein bound. Factors that alter protein binding will affect serum total T4 levels; however, measurement of serum free T4 (the metabolically active moiety) has largely replaced serum total T4 for thyroid status assessment.

Conditions/states that increase TBG binding: Pregnancy, hepatitis, porphyria, neonatal state

Medications that increase TBG binding: Estrogens, 5-fluorouracil, heroin, methadone, mitotane, perphenazine, selective estrogen receptor modulators (eg, tamoxifen, raloxifene)

Conditions/states that decrease TBG binding: Hepatic failure, nephrosis, severe illness

Medications that decrease TBG binding: Androgens, anabolic steroids, glucocorticoids, L-asparaginase, nicotinic acid

Thyroxine (T4) and Triiodothyronine (T3): Serum binding inhibitors (ATA/AACE [Garber 2012]):

Medications that inhibit T4 and T3 binding: Carbamazepine, furosemide, free fatty acids, heparin, NSAIDS (variable, transient), phenytoin, salicylates

Thyroid gland hormone: Interference with production and secretion (ATA/AACE [Garber 2012]):

Medications affecting iodine uptake: Amiodarone, iodinated contrast agents, iodine, ethionamide

Medications affecting hormone production: Amiodarone, ethionamide, iodinated contrast agents, iodine, sulfonylureas, sulfonamides, thionamides (carbimazole, methimazole, propylthiouracil)

Medications affecting secretion: Amiodarone, iodinated contrast agents, iodine, lithium

Medications inducing thyroiditis: Alemtuzumab, amiodarone, antiangiogenic agents (lenalidomide, thalidomide), denileukin diftitoxin, interferon alpha, interleukins, lithium, tyrosine kinase inhibitors (sunitinib, sorafenib)

Medications potentially causing the development of Graves’: Alemtuzumab, interferon alpha, highly active antiretroviral therapy

Medications potentially ameliorating thyroiditis (if autoimmune) or Graves’: Glucocorticoids

Hypothalamic-pituitary axis and TSH: Interference with secretion (ATA/AACE [Garber 2012]):

Medications decreasing TSH secretion: Bexarotene, dopamine, dopaminergic agonists (bromocriptine, cabergoline), glucocorticoids, interleukin-6, metformin, opiates, somatostatin analogues (octreotide, lanreotide), thyroid hormone analogues

Medications increasing TSH secretion: Amphetamine, interleukin 2, metoclopramide, ritonavir, St John's wort

Medications potentially causing hypophysitis: Ipilimumab

Adverse Reactions

1% to 10%: Cardiovascular: Cardiac arrhythmia (6%), tachycardia (3%), hypotension (2%), myocardial infarction (2%)

<1% (Limited to important or life-threatening): Allergic skin reaction, angina pectoris, cardiac failure, fever, hypertension, phlebitis, twitching

ALERT: U.S. Boxed Warning

Weight reduction:

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines, such as those used for their anorectic effects.

Warnings/Precautions

Disease-related concerns:

• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency; symptoms may be exaggerated or aggravated. Treatment with glucocorticoids should precede thyroid replacement therapy in patients with adrenal insufficiency (ATA/AACE [Garber 2012]).

• 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. Increase dose slowly and monitor for signs/symptoms of angina (ATA/AACE [Garber 2012]).

Other warnings/precautions:

• Monitoring: Thyroid replacement requires periodic assessment of thyroid status.

• Weight reduction (off-label use): [US 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.

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.

Alternate recommendations: Adults: Monitor TSH 4 to 8 weeks after treatment initiation or dose changes, 6 months after adequate replacement dose determined, followed by every 12 months thereafter (or more frequently depending on clinical situation) (ATA/AACE [Garber 2012]).

Antidepressant augmentation (off-label use): Adults: Free T3, free T4, and TSH (baseline, recheck at 3 months, and then every 6 months to 1 year at minimum). TSH level should be at least at the lower limit of the normal range [~0.4 milliunits/ml] or below in the absence of hyperthyroid symptoms; free T3 can be maintained at the upper limit of the normal range based on the severity of depressive symptoms and response to T3. In postmenopausal women, bone density should be monitored with densitometry every 2 years (Rosenthal 2011).

Pregnancy Risk Factor

A

Pregnancy Considerations

Endogenous thyroid hormones minimally cross the placenta; the fetal thyroid becomes active around the end of the first trimester. Liothyronine has not been found to increase the risk of teratogenic or adverse effects following maternal use during pregnancy.

Uncontrolled maternal hypothyroidism may result in adverse neonatal and maternal outcomes. To prevent adverse events, normal maternal thyroid function should be maintained prior to conception and throughout pregnancy. Levothyroxine is considered the treatment of choice for the control of hypothyroidism during pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience hair loss. Have patient report immediately to prescriber signs of adrenal gland problems (severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), angina, swelling of arms or legs, tachycardia, abnormal heartbeat, headache, shortness of breath, excessive weight gain, irritability, anxiety, temperature sensitivity, sweating a lot, or menstrual changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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