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.
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 (Ref). Dose ranges of 20 to 62.5 mcg/day have been studied in clinical trials (Ref). Note: The duration of treatment has not been well studied (Ref). 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 (Ref).
Deceased organ donor management (hormonal replacement therapy) (off-label use): Note: Use in hemodynamically unstable patients and/or in potential cardiac donors with a left ventricular ejection fraction <45%. May be used alone or as part of combination hormone therapy (Ref).
IV: 4 mcg bolus, followed by a continuous infusion of 3 mcg/hour (Ref).
Diagnostic aid, T3 suppression test: Oral: 75 to 100 mcg once daily for 7 days. Radioactive iodide uptake is determined before and after administration.
Hypothyroidism, primary (adjunctive agent):
Note: May be considered as an adjunct to levothyroxine in patients with persistent symptoms despite normal TSH levels who underwent thyroidectomy or radioiodine ablation, or whose serum T3 levels are at or below the lower end of the reference range (Ref). Avoid use in patients who are at risk for arrhythmia, are older (eg, >60 years of age), or are pregnant (Ref). Use is not recommended in patients with secondary hypothyroidism (eg, due to hypopituitarism) due to limited data (Ref). Patient should be under the care of a clinician experienced with the use of levothyroxine and liothyronine combination therapy for this condition.
Oral: Initial: ~5% to 6% of the current daily levothyroxine dose (rounded to the nearest 5 mcg/day increment), typically administered in 2 divided daily doses; usual dose range: 5 to 12.5 mcg/day in 2 divided doses. When liothyronine is initiated, reduce the daily levothyroxine dose to 80% to 85% of the original dose. The final levothyroxine to liothyronine dose ratio should be approximately 13:1 to 16:1 (Ref); example dosing is as follows:
Current levothyroxine dose |
New combination regimen with levothyroxine and liothyronineb | |
---|---|---|
New levothyroxine dose |
New liothyronine dose | |
a Adapted with permission from: Ross DS. Treatment of primary hypothyroidism in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed March 2, 2022. Copyright © 2022 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved. | ||
b For use as separate levothyroxine and liothyronine products according to the above conversions. Commercially available combination products are not recommended because they contain a 4:1 ratio mixture of levothyroxine and liothyronine that delivers a supraphysiologic liothyronine dose relative to levothyroxine (ETA [Wiersinga 2012]; Ross 2022). | ||
75 to 100 mcg/day |
50 to 75 mcg/day |
2.5 mcg twice daily |
112 to 137 mcg/day |
88 to 112 mcg/day |
2.5 mcg 3 times daily or 5 mcg every morning and 2.5 mcg every evening |
150 to 175 mcg/day |
112 to 137 mcg/day |
5 mcg twice daily |
200 to 250 mcg/day |
150 to 200 mcg/day |
7.5 mcg every morning and 5 mcg every evening |
Dosage adjustment: Adjust the levothyroxine and/or liothyronine dose every 6 weeks if needed based on TSH levels while maintaining an approximate 13:1 to 16:1 dose ratio of levothyroxine to liothyronine (Ref). An example dosage adjustment strategy is as follows:
TSH above target: If TSH is <10 milliunits/L, increase the levothyroxine dose only; if TSH is ≥10 milliunits/L, also increase the liothyronine dose (eg, by 2.5 mcg/day) (Ref).
TSH below target: If TSH is detectable, generally reduce the liothyronine dose (eg, by 2.5 mcg/day); if TSH is fully suppressed, reduce both levothyroxine and liothyronine doses (Ref).
Duration of therapy: Combination therapy with liothyronine and levothyroxine may be continued indefinitely in patients whose hypothyroid symptoms improve; if hypothyroid symptoms persist after 3 months of euthyroidism with combination therapy, consider switching back to levothyroxine monotherapy (Ref).
Myxedema coma (adjunct to levothyroxine): IV: Initial loading dose of 5 to 20 mcg as a slow bolus, followed by 2.5 to 10 mcg every 8 hours until the patient improves (eg, regains consciousness) and can transition to oral levothyroxine; consider doses on the lower end of the dosing range for smaller or older patients and those with a history of or who are at risk for coronary artery disease or arrhythmia; concomitant glucocorticoid therapy (eg, stress doses of hydrocortisone) is required until the possibility of coexisting adrenal insufficiency is excluded (Ref).
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.
Cardiac symptoms : In patients receiving oral therapy who have developing or worsening cardiac symptoms (eg, angina, arrhythmia), reduce dose or withhold therapy for 7 days, then resume at a reduced dose.
Diagnostic aid , T3 suppression test: Oral: Refer to adult dosing; use with caution and initiate at the low end of dosing range.
Hypothyroidism: Avoid use in older adults (eg, >60 years of age); levothyroxine monotherapy is preferred (Ref).
Myxedema coma: IV: Refer to adult dosing; use with caution and initiate at the low end of the dosing range.
(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 (Ref). 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported for liothyronine sodium injection, unless otherwise noted.
1% to 10%:
Cardiovascular: Acute myocardial infarction (≤2%), angina pectoris (≤1%), cardiac arrhythmia (6%), heart failure (≤1%), hypertension (≤1%), hypotension (≤2%), phlebitis (≤1%), tachycardia (3%)
Nervous system: Twitching (≤1%)
Miscellaneous: Fever (≤1%)
Postmarketing: Dermatologic: Allergic skin reaction (tablets)
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.
• 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; avoid use in patients who are at risk for arrhythmias. 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. Myxedema coma should be treated with injectable thyroid hormone replacement products administered IV.
• Osteoporosis: Thyroid hormone overreplacement may result in increased bone resorption and decreased bone mineral density, especially in postmenopausal patients; use the lowest effective dose to achieve therapy goals.
Special populations:
• Older adults: Use with caution in older adults (eg, >60 years of age); they may be more likely to have compromised cardiovascular function. Increase dose slowly and monitor for signs/symptoms of angina.
May cause transient alopecia in children during first few months of therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Triostat: 10 mcg/mL (1 mL [DSC]) [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
Solution (Liothyronine Sodium Intravenous)
10 mcg/mL (per mL): $528.75
Tablets (Cytomel Oral)
5 mcg (per each): $0.46
25 mcg (per each): $0.64
50 mcg (per each): $1.07
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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 intermittent IV doses at a rate of ≤10 mcg/minute (Ref).
Continuous IV infusion: Cadaveric organ recovery (hormonal resuscitation) (off-label use): After IV bolus administration, may administer as a continuous infusion (Ref).
Oral: Administer at the same time each day.
Note: May be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.
Thyroid disorders: Oral: Replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism; 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.
Antidepressant augmentation; Deceased organ donor management (hormonal replacement therapy)
Liothyronine may be confused with levothyroxine
T3 is an error-prone abbreviation (mistaken as acetaminophen and codeine [ie, Tylenol® #3])
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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
Antacids: May decrease the absorption 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 hours prior to or one hour after bile acid sequestrants, or monitor for decreased serum concentrations and clinical effects of oral thyroid products during coadministration. 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
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
Nirmatrelvir and Ritonavir: May diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
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
Soybean: May diminish the therapeutic effect of Thyroid Products. Risk C: Monitor therapy
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 during pregnancy (ACOG 2020; ATA [Alexander 2017]).
Due to alterations of endogenous maternal thyroid hormones, patients with hypothyroidism who are treated with a thyroid replacement product prior to pregnancy require a dose increase as soon as pregnancy is confirmed (ATA [Alexander 2017]). 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]).
Heart rate, BP, 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 patients).
Primary hypothyroidism: In patients who experience symptomatic improvement following initiation of therapy or dosage adjustment, measure TSH response at 6 weeks and adjust therapy as needed (ATA [Jonklaas 2014]). In those who continue to experience symptoms, consider measuring free T4 (FT4) and TSH at 3 weeks and adjusting the regimen if FT4 is below normal; however, in patients receiving combination therapy with a lower T4 to T3 ratio (eg, 4:1) than is recommended, FT4 levels may be low despite normal TSH levels (Ross 2022a). In patients receiving combination therapy with levothyroxine, the full effect of the dose may not be apparent at 3 weeks as levothyroxine does not achieve steady state until ~6 weeks following initiation or dosage adjustment. Continue to measure serum TSH (and FT4 if steady state has not yet been achieved) every 3 to 6 weeks and adjust the regimen until the TSH concentration is within the goal range (ATA [Jonklaas 2014]; Ross 2022a).
Note: Measurement of TSH is not adequate to guide treatment in patients with secondary hypothyroidism (eg, due to hypopituitarism) (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
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