(LYE oh triks)
- Levothyroxine and Liothyronine
- Liothyronine and Levothyroxine
- T3/T4 Liotrix
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]
Brand Names: U.S.
- Thyroid Product
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
Onset of Action
Liothyronine (T3): ~3 hours
Time to Peak
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
Special Populations Note
T4 absorption and urinary excretion are decreased with age.
Use: Labeled Indications
Replacement or supplemental therapy in hypothyroidism (uniform mixture of T4:T3 in 4:1 ratio by weight)
Thyroid-stimulating hormone (TSH) suppressant therapy used in the management of thyroid cancer (levothyroxine is generally recommended for this indication); prevention or treatment of euthyroid goiters (eg, thyroid nodules, subacute or chronic lymphocytic thyroiditis [Hashimoto’s], multinodular goiters)
Diagnostic agent in suppression tests to diagnose suspected mild hyperthyroidism or to demonstrate thyroid gland autonomy
Hypersensitivity to liotrix or any component of the formulation; uncorrected adrenal insufficiency; untreated thyrotoxicosis
Hypothyroidism: Oral: Initial: Levothyroxine 25 mcg/liothyronine 6.25 mcg once daily; may increase by levothyroxine 12.5 mcg/liothyronine 3.1 mcg every 2-3 weeks. 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 (usual maintenance dose: levothyroxine 50-100 mcg/liothyronine 12.5-25 mcg)
Initial: Levothyroxine 12.5-25 mcg/liothyronine 3.1-6.25 mcg once daily; may increase by levothyroxine 12.5 mcg/liothyronine 3.1 mcg every 2-3 weeks
Congenital hypothyroidism: Oral: Note: In newly diagnosed infants, begin therapy with full dose.
Children 0-6 months: Levothyroxine 12.5-25 mcg/liothyronine 3.1-6.25 mcg once daily
Children 6-12 months: Levothyroxine 25-37.5 mcg/liothyronine 6.25-9.35 mcg once daily
Children 1-5 years: Levothyroxine 37.5-50 mcg/liothyronine 9.35-12.5 mcg once daily
Children 6-12 years: Levothyroxine 50-75 mcg/liothyronine 12.5-18.75 mcg once daily
Children >12 years: Levothyroxine 75 mcg/liothyronine 18.75 mcg once daily
Also see individual agents.
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.
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
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
Mediations increasing TSH secretion: Amphetamine, interleukin 2, metoclopramide, ritonavir, St John's wort
Medications potentially causing hypophysitis: Ipilimumab
Frequency not defined.
Cardiovascular: Blood pressure increased, cardiac arrhythmia, chest pain, palpitation, tachycardia
Central nervous system: Anxiety, ataxia, fever, headache, insomnia, nervousness
Dermatologic: Alopecia, hyperhydrosis, pruritus, urticaria
Endocrine & metabolic: Changes in menstrual cycle, increased appetite, weight loss
Gastrointestinal: Abdominal cramps, constipation, diarrhea, nausea, vomiting
Neuromuscular & skeletal: Hand tremor, myalgia, tremor
Miscellaneous: Allergic skin reactions (rare), diaphoresis
• 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 with caution and initiate therapy at a lower dose 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; 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]).
• Infertility (unapproved use): Use is not justified for the treatment of male or female infertility in euthyroid patients.
• 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.
T4, TSH, heart rate, blood pressure, 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]).
Pregnancy Risk Factor
Endogenous thyroid hormones minimally cross the placenta; the fetal thyroid becomes active around the end of the first trimester. Liotrix has not been found to increase the risk of 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.
• 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 angina, tachycardia, arrhythmia, headache, shortness of breath, irritability, anxiety, tremors, insomnia, temperature sensitivity, sweating a lot, lack of appetite, more hungry, excessive weight gain or loss, diarrhea, vomiting, or menstrual irregularities (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 healthcare 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.