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(LYE oh triks)
Hypothyroidism: Replacement or supplemental therapy in hypothyroidism
Note: Clinical practice guidelines currently do not recommend routine use of levothyroxine/liothyronine combinations over levothyroxine monotherapy in the management of hypothyroidism (ATA [Jonklaas 2014]).
Hypersensitivity to liotrix or any component of the formulation; uncorrected adrenal insufficiency; untreated thyrotoxicosis
Drugs with thyroid hormone activity, alone or 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.
Initial: Levothyroxine 25 mcg/liothyronine 6.25 mcg once daily; a lower initial dose (levothyroxine 12.5 mcg/liothyronine 3.1 mcg) is recommended in patients with long-standing myxedema, especially if cardiovascular impairment coexists (if angina occurs, reduce dose). Dose may be increased in increments of levothyroxine 12.5 mcg/liothyronine 3.1 mcg every 2 to 3 weeks.
Usual maintenance dose: Levothyroxine 50 to 100 mcg/liothyronine 12.5 to 25 mcg once daily; inadequate response despite adequate dosage replacement may indicate nonadherence, poor absorption, excessive elimination, or inactivity of the preparation.
Hypothyroidism: Oral: Initial: Levothyroxine 12.5 to 25 mcg/liothyronine 3.1 to 6.25 mcg once daily; may increase by levothyroxine 12.5 mcg/liothyronine 3.1 mcg every 2 to 3 weeks
Note: Doses should be adjusted based on clinical response and laboratory parameters; guidelines do not recommend routine use of levothyroxine/liothyronine combinations over levothyroxine monotherapy in the management of hypothyroidism (AAP 2006; ATA [Jonklaas 2014]).
Congenital hypothyroidism: Note: Infants should have therapy initiated at full doses. Oral: Usual daily dosage range:
Infants ≤6 months: Liothyronine (T3): 3.1 to 6.25 mcg/levothyroxine (T4): 12.5 to 25 mcg once daily
Infants >6 to 12 months: Liothyronine (T3): 6.25 to 9.35 mcg/levothyroxine (T4): 25 to 37.5 mcg once daily
Children 1 to 5 years: Liothyronine (T3): 9.35 to 12.5 mcg/levothyroxine (T4): 37.5 to 50 mcg once daily
Children 6 to 12 years: Liothyronine (T3): 12.5 to 18.75 mcg/levothyroxine (T4): 50 to 75 mcg once daily
Adolescents: Typical doses > Liothyronine (T3): 18.75 mcg; levothyroxine (T4): 75 mcg once daily
Take once a day on an empty stomach 30-60 minutes before meals.
Store at 2°C to 8°C (36°F to 46°F). Protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Thyrolar: 1/4 [levothyroxine sodium 12.5 mcg and liothyronine sodium 3.1 mcg]
Thyrolar: 1/2 [levothyroxine sodium 25 mcg and liothyronine sodium 6.25 mcg]
Thyrolar: 1 [levothyroxine sodium 50 mcg and liothyronine sodium 12.5 mcg]
Thyrolar: 2 [levothyroxine sodium 100 mcg and liothyronine sodium 25 mcg]
Thyrolar: 3 [levothyroxine sodium 150 mcg and liothyronine sodium 37.5 mcg]
Amezinium: Thyroid Products may enhance the stimulatory effect of Amezinium. Monitor therapy
Amiodarone: May diminish the therapeutic effect of Thyroid Products. Monitor therapy
Apalutamide: May diminish the therapeutic effect of Thyroid Products. 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. 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
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. 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
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. Monitor therapy
Growth Hormone Analogs: May diminish the therapeutic effect of Thyroid Products. 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. 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
Ritonavir: May diminish the therapeutic effect 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. 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. 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
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]); T4, heart rate, blood pressure, new/worsened cardiac symptoms (eg, chest pain, palpitations, edema), clinical signs of hypo- and hyperthyroidism; TSH is the most reliable guide for evaluating adequacy of thyroid replacement dosage in primary thyroid dysfunction. 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. Free T4 (not TSH) should be monitored to guide treatment in patients with central hypothyroidism (ATA/AACE [Garber 2012]).
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, 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
Frequency not defined.
Cardiovascular: Cardiac arrhythmia, chest pain, increased blood pressure, palpitations, tachycardia
Central nervous system: Anxiety, ataxia, headache, insomnia, nervousness
Dermatologic: Alopecia, diaphoresis, pruritus, urticaria
Endocrine & metabolic: Menstrual disease, weight loss
Gastrointestinal: Abdominal cramps, constipation, diarrhea, increased appetite, nausea, vomiting
Neuromuscular & skeletal: Myalgia, tremor, tremor of hands
<1%, postmarketing, and/or case reports: Allergic skin reaction
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency; symptoms may be exaggerated or aggravated; contraindicated in patients with uncorrected adrenal insufficiency. Treatment with glucocorticoids should precede thyroid replacement therapy in patients with adrenal insufficiency (ATA/AACE [Garber 2012]).
• 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 and insipidus; symptoms may be exaggerated or aggravated.
• Myxedema: Use with caution in patients with myxedema; symptoms may be exaggerated or aggravated; initial dosage reduction is recommended in patients with long-standing myxedema.
• Elderly: Use with caution in the elderly as these patients are more likely to have compromised cardiovascular function; lower initial dosage is recommended. Suppressed TSH levels may increase risk of atrial fibrillation and mortality secondary to cardiovascular disease (Gharib 2010; Parle 2001). Increase dose slowly and monitor for signs/symptoms of angina (ATA/AACE [Garber 2012]).
• Weight reduction (unapproved use): [US Boxed Warning]: In euthyroid patients, 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.
Liotrix has not been found to increase the risk of adverse effects following maternal use during pregnancy.
Maternal hypothyroidism, however, can be associated with adverse effects in 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 148 2015; ATA [Alexander 2017]).
Thyroid replacement therapy minimizes the risk of adverse pregnancy outcomes in females with overt hypothyroidism and treatment is recommended during pregnancy (ACOG 148 2015; 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 148 2015; ATA [Alexander 2017]; ES [De Groot 2012]). However, maternal supplementation with liotrix does not provide the fetus with sufficient concentrations of T4 required for the developing fetal brain. Therefore, liotrix is not the preferred treatment of maternal hypothyroidism and should not be used in pregnant females (ACOG 148 2015; 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]).
The primary active compound is T3 (triiodothyronine), which may be converted from T4 (thyroxine) and then circulates throughout the body to influence growth and maturation of various tissues. Liotrix is uniform mixture of synthetic T4 and T3 in 4:1 ratio; 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
Thyroxine (T4): 40% to 80%; T3: 95%
Hepatic to triiodothyronine (active); ~80% T4 deiodinated in kidney and periphery; glucuronidation/conjugation also occurs; undergoes enterohepatic recirculation
Urine (major route of elimination); partially feces
Liothyronine (T3): ~3 hours
Serum: T4: 2-4 hours; T3: 2-3 days
T4: Euthyroid: 6-7 days; Hyperthyroid: 3-4 days; Hypothyroid: 9-10 days
T3: 2.5 days
T4: >99% bound to plasma proteins including thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin
What is this drug used for?
• It is used to add thyroid hormone to the body.
• It is used to treat or prevent an enlarged thyroid gland.
• It is used to manage thyroid cancer.
• It may be given to you for other reasons. Talk with the doctor.
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Hair loss (children)
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Chest pain
• Fast heartbeat
• Abnormal heartbeat
• Shortness of breath
• Trouble sleeping
• Temperature sensitivity
• Sweating a lot
• Leg cramps
• Muscle weakness
• Abdominal cramps
• Lack of appetite
• Increased hunger
• Excessive weight gain or loss
• Swelling of arms or legs
• Lump on neck
• Menstrual changes
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.