Thyroid hormones, including liothyronine, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. 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.
Hypothyroidism: Oral: Initial: 25 mcg once daily; may increase by up to 25 mcg/day every 1 to 2 weeks; usual maintenance dose: 25 to 75 mcg once daily
Patients with cardiovascular disease: Initial: 5 mcg once daily; may increase by 5 mcg/day every 2 weeks.
Conversion to liothyronine from thyroid (desiccated) or levothyroxine: Discontinue the other medication, initiate a low dose of liothyronine, and increase gradually according to response. Liothyronine has a rapid onset of action; residual effects of other thyroid preparation may persist for the first several weeks into therapy.
Myxedema coma: IV:
Adjunctive therapy in combination with levothyroxine: Initial: 5 to 20 mcg loading dose; maintenance: 2.5 to 10 mcg every 8 hours; continue therapy as clinically indicated. Lower dosages should be considered for patients who are small, elderly, or have coronary artery disease or arrhythmia. Avoid high doses due to risks associated with high serum triiodothyronine levels (ATA [Jonklaas 2014]).
Note: Normally, at least 4 hours should be allowed between IV 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.
Conversion to liothyronine tablets from injectable liothyronine: Discontinue the injectable, initiate oral therapy at a low dosage, and increase gradually according to response.
Suppression test (T3): Oral: 75 to 100 mcg once daily for 7 days. Radioactive iodide uptake is determined before and after administration.
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; SCCM/ACCP/AOPO [Kotloff 2015]; Zaroff 2002).
Prevention of memory deficit with ECT (off-label use): Oral: 50 mcg once daily administered from the day before beginning of ECT and every morning until the last session (Mohagheghi 2015). Additional data may be necessary to further define the role of liothyronine in this setting.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. Liothyronine undergoes substantial renal excretion.
There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Liothyronine: Pediatric drug information")
Congenital hypothyroidism: Note: Guidelines do not recommend routine use of liothyronine over levothyroxine monotherapy in the management of hypothyroidism (AAP 2006; ATA [Jonklaas 2014]). Infants, Children, and Adolescents: Oral: Initial: 5 mcg/day; increase by 5 mcg every 3 to 4 days
Usual maintenance dose:
Infants: 20 mcg/day
Children 1 to 3 years: 50 mcg/day
Children >3 years and Adolescents: 25 to 75 mcg/day
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution. Liothyronine undergoes substantial renal excretion.
There are no dosage adjustments provided in the manufacturer’s labeling.
Hypothyroidism: Oral: 5 mcg once daily; increase by 5 mcg/day every 2 weeks.
Myxedema coma: IV: Refer to adult dosing; use with caution and initiate at the low end of the dosing range.
Suppression test (T3): Oral: Refer to adult dosing; use with caution and initiate at the low end of dosing range.
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
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Cytomel: 5 mcg, 25 mcg
Generic: 5 mcg, 25 mcg
IV: For IV use only; do not administer IM or SubQ
Intermittent IV administration: Administer at a rate of 10 mcg/minute (Gahart 2014).
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).
Oral: Administer at the same time each day.
Thyroid disorders: Oral: Replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism; adjunct to surgery and radioiodine therapy in the management of well-differentiated thyroid cancer; a diagnostic agent in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy.
Limitations of use: Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients; not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.
Myxedema coma: IV: Treatment of myxedema coma.
Note: May be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.
Antidepressant augmentation; Cadaveric organ recovery (hormonal resuscitation); Prevention of memory deficit with electroconvulsive therapy (ECT)
Liothyronine may be confused with levothyroxine
T3 is an error-prone abbreviation (mistaken as acetaminophen and codeine [ie, Tylenol® #3])
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%: Cardiovascular: Cardiac arrhythmia (6%), tachycardia (3%), hypotension (≤2%), myocardial infarction (≤2%)
<1%, postmarketing, and/or case reports: Allergic skin reaction, angina pectoris, cardiac failure, fever, hypertension, phlebitis, twitching
Injection: Hypersensitivity to liothyronine sodium or any component of the formulation; uncorrected adrenal insufficiency; untreated thyrotoxicosis; concurrent use with artificial rewarming of patient
Oral: Uncorrected adrenal insufficiency
Canadian labeling: Additional contraindications (not in the US labeling): Acute myocardial infarction
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. Use is contraindicated in patients with uncorrected adrenal insufficiency.
• Cardiovascular disease: Use reduced initial dosage and conservative dose titration in patients with cardiovascular disease. Overtreatment may increase risk of adverse cardiovascular events including angina and arrhythmia; patients with developing or worsening cardiac symptoms should have their dose reduced or therapy withheld for 7 days and then resumed at a reduced dose. Chronic untreated hypothyroidism predisposes patients to cardiovascular disease (ATA [Jonklaas 2014]; Razvi 2018).
• Diabetes: Use with caution in patients with diabetes mellitus (may worsen glycemic control).
• Myxedema: Use with caution in patients with myxedema because symptoms may be exaggerated or aggravated. Initiate therapy at a low dose and increase gradually. Myxedema coma should be treated with injectable thyroid hormone replacement products administered IV.
• Osteoporosis: Long-term therapy can decrease bone mineral density. Postmenopausal women and women using suppressive doses should receive the lowest dose necessary for clinical response.
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.
Other warnings/precautions:
• Weight reduction (off-label use): [US Boxed Warning]: Thyroid hormones, including liothyronine, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. 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.
May cause transient alopecia in children during first few months of therapy.
None known.
Amezinium: Thyroid Products may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Amiodarone: May diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Apalutamide: May diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Calcium Polystyrene Sulfonate: May decrease the serum concentration of Thyroid Products. Management: Consider administering thyroid products at least 4 hours prior to calcium polystyrene sulfonate. Monitor for signs and symptoms of hypothyroidism with concomitant use. 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. Monitor for decreased therapeutic effects of thyroid products if an oral calcium supplement is initiated/dose increased. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
Cardiac Glycosides: Thyroid Products may decrease the serum concentration of Cardiac Glycosides. Specifically, returning to a euthyroid state from a hypothyroid state may decrease the serum concentration of cardiac glycosides. Risk C: Monitor therapy
Ciprofloxacin (Systemic): 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
Furosemide: May decrease the protein binding of Thyroid Products. This may lead to a transient increase in free thyroid hormone concentrations and to a later decrease in total thyroid hormone concentrations. Risk C: Monitor therapy
Growth Hormone Analogs: May diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Thyroid Products. Management: Separate the administration of thyroid products and lanthanum by at least 4 hours. Risk D: Consider therapy modification
PHENobarbital: May decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites. Risk C: 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. Risk C: Monitor therapy
Primidone: May decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
RifAMPin: May decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
Ritonavir: May diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy
Sodium Iodide I131: Thyroid Products may diminish the therapeutic effect of Sodium Iodide I131. Management: Discontinue thyroid products before sodium iodide I-131 administration, and avoid concurrent use. Stop triiodothyronine (T3) 2 weeks before, and stop thyroxine (T4) 4 weeks before, sodium iodide I-131 administration. Risk X: Avoid combination
Sodium Polystyrene Sulfonate: May decrease the serum concentration of Thyroid Products. Management: Consider administering thyroid products at least 4 hours prior to sodium polystyrene sulfonate. Monitor for signs and symptoms of hypothyroidism with concomitant use. Risk D: Consider therapy modification
Theophylline Derivatives: Thyroid Products may increase the metabolism of Theophylline Derivatives. Risk C: Monitor therapy
Tricyclic Antidepressants: Thyroid Products may enhance the arrhythmogenic effect of Tricyclic Antidepressants. Thyroid Products may enhance the stimulatory effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Thyroid Products may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Overt hypothyroidism increases the risk of irregular menses and infertility; thyroid replacement is recommended to normalize thyroid function in infertile patients with overt hypothyroidism who desire to become pregnant. Thyroid replacement may also be used in infertile patients with subclinical hypothyroidism using assisted reproductive techniques to become pregnant; however, liothyronine is not the preferred thyroid replacement agent (ATA [Alexander 2017]).
Liothyronine has not been found to increase the risk of teratogenic or adverse effects following maternal use during pregnancy; however, normal levels of maternal thyroid hormones are required for fetal development. Untreated maternal hypothyroidism can be associated with adverse effects in both the mother and fetus, including spontaneous abortion, stillbirth, premature birth, low birth weight, impaired neurocognitive development in the offspring, abruptio placentae, gestational hypertension, and preeclampsia (ACOG 2020; ATA [Alexander 2017]).
Thyroid replacement therapy minimizes the risk of adverse pregnancy outcomes in patients with overt hypothyroidism and treatment is recommended for all patients with overt hypothyroidism during pregnancy (ACOG 2020; ATA [Alexander 2017]); however, maternal supplementation with liothyronine does not provide the fetus with sufficient concentrations of T4 required for the developing fetal brain. Therefore, liothyronine is not the preferred treatment of maternal hypothyroidism and should not be used in pregnant patients (ACOG 2020; ATA [Alexander 2017]; ES [De Groot 2012]).
Thyroid replacement therapy minimizes the risk of adverse pregnancy outcomes in females with overt hypothyroidism and treatment is recommended during pregnancy (ACOG 2020; ATA [Alexander 2017]). Thyroid replacement therapy is also recommended in some cases of subclinical hypothyroidism during pregnancy and overt hypothyroidism in females with postpartum thyroiditis (ACOG 2020; ATA [Alexander 2017]; ES [De Groot 2012]). However, maternal supplementation with liothyronine does not provide the fetus with sufficient concentrations of T4 required for the developing fetal brain. Therefore, liothyronine is not the preferred treatment of maternal hypothyroidism and should not be used in pregnant females (ACOG 2020; ATA [Alexander 2017]; ES [De Groot 2012]).
Due to alterations of endogenous maternal thyroid hormones, hypothyroid patients treated with a thyroid replacement product prior to pregnancy require a dose increase as soon as pregnancy is confirmed (ATA [Alexander 2017]; ES [De Groot 2012]). Close monitoring of pregnant patients is recommended (ATA [Alexander 2017]).
Liothyronine is present in breast milk.
Adequate thyroid hormone concentrations are required to maintain normal lactation. Patients with overt hypothyroidism or subclinical hypothyroidism experiencing poor lactation and who wish to breastfeed should be treated (ATA [Alexander 2017]).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. When thyroid replacement therapy is needed in patients who are breastfeeding, liothyronine is not the preferred thyroid replacement agent (ATA [Alexander 2017]).
Thyroid-stimulating hormone (TSH) 4 to 6 weeks after treatment initiation or dose changes, 4 to 6 months after adequate replacement dose determined, followed by every 12 months thereafter (or more frequently depending on clinical situation) (ATA [Jonklaas 2014]); heart rate, blood pressure, new/worsened cardiac symptoms (eg, chest pain, palpitations, edema); clinical signs of hypo- and hyperthyroidism; bone mineral density (particularly with long-term use in postmenopausal women).
Note: TSH is the most reliable guide for evaluating adequacy of thyroid replacement dosage in primary thyroid dysfunction; however, measurement of TSH is not adequate to guide treatment in patients with central hypothyroidism (ATA/AACE [Garber 2012]; ES [Fleseriu 2016]).
Myxedema coma: Monitor thyroid function tests (FT4 or T4, T3) every 1 to 2 days; serial assessment of TSH trends may also be considered to determine trend towards improvement. Monitor clinical response (eg, mental status, temperature, respiratory function, cardiovascular status, electrolytes [eg, serum sodium]) to ensure adequate parenteral thyroid hormone replacement; monitor also for safety with parenteral therapy (eg, tachycardia, arrhythmia, myocardial infarction) (ATA [Jonklaas 2014]).
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.
T4 (thyroxine) serum concentrations: Adults: ~4 to 12 mcg/dL (SI: 51 to 154 nmol/L). Note: Normal range in pregnancy: ~5.5 to 16 mcg/dL (SI: ~71 to 206 nmol/L)
T4 free (free thyroxine; free T4) serum concentrations: Adults: 0.7 to 1.8 ng/dL (SI: 9 to 23 pmol/L).
T3 total (triiodothyronine; total T3) serum concentrations: Adults: 80 to 230 ng/dL (SI: 1.2 to 3.5 nmol/L).
Thyroid-stimulating hormone (TSH) serum concentrations: Adults: Varies by laboratory and assay used; refer to laboratory provided reference range. If an upper and lower limit of normal for a third generation TSH assay is not available, a reference range of 0.45 to 4.12 milliunits/L should be considered (ATA/AACE [Garber 2012]). A higher target range of 4 to 6 milliunits/L has been suggested in patients >70 years (ATA [Jonklaas 2014]).
Subclinical hypothyroidism (elevated TSH; free T4 within normal range):
Severe (TSH ≥10 milliunits/L): These patients are at increased risk for heart failure and cardiovascular mortality and should be considered for treatment with levothyroxine (ATA/AACE [Garber 2012]; ETA [Pearce 2013]).
Mild to moderate (TSH 4 to 10 milliunits/L): Decision for when to treat should be tailored to individual patient based on age, symptoms, and cardiovascular risk (ATA/AACE [Garber 2012]; ETA [Pearce 2013]).
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
Onset of action: Oral: Within a few hours
Peak response: Oral: 2 to 3 days
Absorption: Oral: Well absorbed (95% in 4 hours)
Half-life elimination: 0.75 days (Brent 2011)
Excretion: Urine (primary); Feces
Solution (Liothyronine Sodium Intravenous)
10 mcg/mL (per mL): $481.25
Solution (Triostat Intravenous)
10 mcg/mL (per mL): $481.50
Tablets (Cytomel Oral)
5 mcg (per each): $2.40
25 mcg (per each): $3.16
50 mcg (per each): $4.83
Tablets (Liothyronine Sodium Oral)
5 mcg (per each): $0.79 - $2.20
25 mcg (per each): $1.04 - $2.89
50 mcg (per each): $1.59 - $4.41
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