Liothyronine Sodium Capsules

Liothyronine (L-triiodothyronine or L-T3) is a synthetic sodium salt of the endogenous thyroid hormone triiodothyronine (T3). The oral tablet is indicated for use as replacement or supplemental therapy in the treatment of hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis; as a pituitary thyroid-stimulating hormone (TSH) suppressant in the treatment or prevention of various types of euthyroid goiters; and as a diagnostic agent in T3 suppression tests. Liothyronine injection is indicated for intravenous use in the treatment of myxedema coma/precoma. Either form of liothyronine may be used for patients who are allergic to desiccated thyroid or thyroid extract derived from pork or beef. Supraphysiologic thyroid hormone concentrations may occur following orally administered liothyronine, but not after intravenous administration. Liothyronine is potentially more cardiotoxic than levothyroxine. However, due to the faster onset of action and the need to peripherally convert levothyroxine (T4) to the biologically active T3, liothyronine has been recommended for treatment of myxedema coma. There are no comparative studies available. Levothyroxine is generally considered the most appropriate of the thyroid replacement agents for long-term treatment of hypothyroidism. However, a small randomized clinical trial demonstrated improvement in mood and neuropsychological function of hypothyroid patients with partial substitution of liothyronine for levothyroxine.^[1] Liothyronine received approval for use by the FDA in 1954.

Thyroid hormones increase the body’s metabolic rate, enhancing oxygen consumption by most tissues of the body. They exert a profound effect on virtually every organ system in the body, being especially important in the development of the central nervous system. Liothyronine exhibits the actions of the biologically active form of the endogenous thyroid hormone, triiodothyronine. T3 is four times more active than T4, but lower serum levels are maintained. In vitro studies indicate that T3 increases aerobic mitochondrial function, which increases the rate of synthesis and utilization of high-energy myocardial phosphates. Through stimulation of myosin ATPase tissue lactic acid is reduced. It is now well-established that 80% of circulating T3 results from peripheral conversion of T4, with the remainder secreted from the thyroid gland. Approximately 45% of T4 is converted to inactive reverse T3 (rT3) and 35% to 40% to biologically active T3. Iodothyronine 5′-deiodinase, the membrane bound enzyme responsible for extrathyroidal conversion, has the greatest activity in the liver and kidney. Enzymatic conversion also occurs through a PTU-insensitive 5′-deiodinase found primarily in the pituitary and central nervous system. Conversion may be inhibited during times of stress or illness, diverting T4 to the inactive reverse T3 (rT3). It seems that the binding of T3 to a nuclear thyroid hormone receptor initiates the majority of the effects produced in the tissues by thyroid hormones. Most synthetic and natural thyroid hormone analogs will bind to this protein, but T3 has a ten times greater receptor affinity than does T4.

The release of T3 and T4 from the thyroid gland into the systemic circulation is regulated by TSH (thyrotropin), which is secreted by the anterior pituitary gland. Thyrotropin release is controlled by the secretion of thyroid-releasing hormone (TRH) from the hypothalamus and by a feedback mechanism dependent on the concentrations of circulating thyroid hormones. Because of this feedback mechanism, the administration of pharmacological doses of exogenous thyroid hormones, including liothyronine, to patients with normal thyroid function suppresses endogenous thyroid hormone secretion.

Correction of hypothyroidism through administration of liothyronine or other thyroid hormones will increase cardiac consumption, resulting in increased cardiac output, ventricular contractility and heart rate with a decrease in total systemic vascular resistance. An increase in the rate and depth of respiration, vasodilation, motility of the gastrointestinal tract and an improved return to consciousness are also produced. Thyroid hormones increase the metabolic rate, which corrects hypothermia, by enhancing protein and carbohydrate metabolism, increasing gluconeogenesis, facilitating the mobilization of glycogen stores, and increasing protein synthesis. The number and activity of mitochondria in almost all cells of the body is increased. In primary hypothyroidism, thyroid stimulating hormone (TSH) levels should correct when normal levels of thyroid hormone are established.

General cautions include hypersensitivity to active or extraneous constituents of liothyronine injection or tablets. Inactive tablet ingredients can include calcium sulfate, gelatin, starch, stearic acid, sucrose, and talc. Liothyronine injection and tablets may be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.

Liothyronine is contraindicated for use in patients with untreated thyrotoxicosis of any etiology. Use caution when administering liothyronine to patients with autonomous thyroid tissue to prevent precipitation of thyrotoxicosis.

Liothyronine is contraindicated for use in patients with diagnosed but untreated adrenal insufficiency. Adrenal insufficiency should be corrected prior to or during concomitant administration of thyroid agents. Administration of thyroid hormones to patients with uncontrolled adrenal insufficiency can cause adrenal crisis due to an increase in the body’s demand for adrenal hormones. Symptoms of adrenal insufficiency can be unmasked or exacerbated by the administration of thyroid agents. Supplemental adrenocortical steroids may be necessary to meet the body’s increased demand for adrenal hormones.

Secondary causes of hypothyroidism (e.g., morphologic hypogonadism and nephroses) should be ruled out prior to beginning treatment with liothyronine. Patients with hypothyroidism secondary to hypopituitarism are likely to have suppressed adrenal function as well, which should be corrected prior to initiating thyroid replacement therapy. Symptoms of hypopituitarism can be unmasked or exacerbated by the administration of thyroid hormones.

Liothyronine should be used cautiously in patients with an acute myocardial infarction that is not associated with hypothyroidism; small amounts of liothyronine may be used only if the MI is complicated or caused by hypothyroidism. Thyroid agents are cardiostimulatory and should be used with great caution in patients with angina pectoris or other preexisting cardiac disease, including uncontrolled hypertension, cardiac arrhythmias, coronary artery disease, or a previous myocardial infarction. Many authorities recommend lower initial dosages and slower titration of thyroid hormones in patients with heart disease (see Dosage). If adverse cardiac symptoms develop or worsen, reduce or withhold liothyronine and cautiously restart at a lower dose. Overtreatment with thyroid hormones may cause cardiac stimulation and lead to increased heart rate, cardiac wall thickening and increased cardiac contractility, which may precipitate angina or cardiac arrhythmias. Concomitant administration of liothyronine with sympathomimetic agents in patients with coronary artery disease may precipitate coronary insufficiency and associated symptoms. Patients with coronary artery disease who are receiving thyroid hormones may be at a higher risk for developing arrhythmias, particularly during surgery.

Caution should be used in geriatric patients since they may be more sensitive to the cardiac effects of thyroid replacement with liothyronine, and are more likely to have concomitant diseases or drug therapy. Lower initial dosages and slower titration are recommended. Individualize dosage.

Liothyronine is known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with renal impairment or renal failure. Care should be taken in dosage selection for these patients; lower initial dosages and slower titration may be needed.

Symptoms of other endocrine disorders, such as diabetes mellitus, can be unmasked or exacerbated by the administration of thyroid agents. Liothyronine therapy can alter the dosage requirements of antidiabetic agents. Blood glucose should be monitored closely during concomitant therapy, particularly during initiation or discontinuation of therapy. Withdrawal of thyroid agents can cause hypoglycemia in susceptible patients.

The use of liothyronine for obesity treatment is not recommended. Normal daily doses are ineffective for weight loss in euthyroid individuals. Larger doses may produce serious manifestations of toxicity, especially if used with anorexic agents such as the sympathomimetic amines.

Myxedematous patients show increased sensitivity to thyroid agents. Initiate therapy with low doses of liothyronine and increase gradually. Simultaneous administration of glucocorticoids is required for treatment of myxedema coma. Some patients with myxedema have inappropriate secretion of ADH and are susceptible to water intoxication. Hyponatremia is frequently present in myxedema coma, but usually resolves without specific therapy as the metabolic status of the patient improves with thyroid treatment; however, use great care in administration of intravenous fluids in combination with liothyronine injection to prevent cardiac decompensation. Although patients in myxedema coma often suffer from hypothermia, artificial rewarming is not recommended with concomitant use of intravenous liothyronine. Peripheral vasodilation produced by external heat further decreases circulation to vital internal organs and may increase shock if present. Administration of liothyronine may restore normal body temperature within 24 to 48 hours if heat loss is prevented by keeping the patient covered with blankets in a warm room.

Some experts question the use of liothyronine for the treatment of cretinism in children and infants; liothyronine (T3) may not significantly cross the blood-brain barrier and may be of limited efficacy. Safety and efficacy of IV liothyronine therapy in children, infants, or neonates have not been established.

Liothyronine is classified in FDA pregnancy risk category A. Thyroid hormones undergo minimal placental transfer and human experience does not indicate adverse fetal effects; do not discontinue needed replacement during pregnancy.^[2] Also, hypothyroidism that is diagnosed during pregnancy should be promptly treated. Measure TSH during each trimester to gauge adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose, monitor thyroid function tests 6—8 weeks postpartum to assess for needed adjustments.

Thyroid hormones, like liothyronine, are generally compatible with breast-feeding; minimal amounts of thyroid hormones are excreted in breast milk.^[3] Thyroid hormones do not have a known tumorigenic potential and are not associated with serious adverse reactions in nursing infants. However, use caution when administering liothyronine to a nursing woman;^[2] changes in thyroid status in the post-partum period may require careful monitoring and maternal dosage adjustment. It should be noted that in general, adequate thyroid status is needed to maintain normal lactation, and there is no reason maternal replacement should be halted due to lactation alone. Levothyroxine is often the preferential drug to treat hypothyroidism and is considered compatible with breast feeding.^[3]

Liothyronine use is only justified for treatment of female or male infertility if such infertility is accompanied by hypothyroidism.

Long-term use of thyroid hormones, like liothyronine, has been associated with decreased bone mineral density, particularly in postmenopausal females on greater than replacement doses or in any women receiving suppressive doses. Patients should be given the minimum dose necessary for desired clinical and biochemical response to limit risks for osteoporosis.

This list may not include all possible contraindications.

Possible interactions include: amiodarone; antacids; anti-thyroid medicines;calcium supplements; carbamazepine; cholestyramine; colestipol; digoxin; female hormones, including contraceptive or birth control pills; iron supplements; ketamine; liquid nutrition products like Ensure; medicines for colds and breathing difficulties; medicines for diabetes; medicines for mental depression; medicines or herbals used to decrease weight or appetite; phenobarbital or other barbiturate medications; phenytoin; prednisone or other corticosteroids; rifabutin; rifampin; soy isoflavones;sucralfate; theophylline; warfarin.

NOTE: Many drugs affect thyroid hormone pharmacokinetics, metabolism or in vivo pharmacodynamics; such drugs may alter the therapeutic response to thyroid hormone replacement. The following medication list is not complete, consult specialized resources for drug-thyroidal axis interactions that may occur.

Antithyroid agents should not be administered with the thyroid hormones due to their opposing effects.^[4] However, iodide and drugs that contain pharmacological amounts of iodine including radiopaque contrast agents that contain iodine (e.g., iohexol, ioversol, iopamidol, and iodixanol) may cause either hypothyroidism or hyperthyroidism in previously euthyroid patients. Patients receiving liothyronine and drugs that contain iodine should be monitored for changes in thyroid function.

Certain foods, beverages, and enteral feedings can inhibit the absorption of thyroid hormones.^[5][6] To minimize the risk of an interaction, thyroid hormones should be administered on an empty stomach with a glass of water at least 30—60 minutes prior to food or enteral feedings. Foods that may decrease thyroid hormone absorption include soybean flour and soy-based infant formulas or enteral feedings, as well as high fiber diets, cottonseed meal, and walnuts. In addition to decreasing the oral absorption of thyroid hormones, limited data indicate that soy containing foods and supplements may also influence thyroid physiology. Concentrated soy isoflavones (e.g., genistein and daidzein) may interfere with thyroid peroxidase catalyzed iodination of thyroglobulin, resulting in a decreased production of thyroid hormones and an increased secretion of TSH endogenously.^[7] More studies are required to assess the exact mechanism of this interaction. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones.^[5] Limited data show that coffee has the potential to impair T4 intestinal absorption. In one report, T4 intestinal absorption was evaluated after the administration of 200 mcg L-thyroxine (L-T4) swallowed with coffee/espresso, water, or water followed 60 minutes later by coffee/espresso. Researchers found that administration with coffee/espresso significantly lowered average serum T4 (p<0.001) and peak serum T4 concentrations (p<0.05) when compared to L-T4 taken with water alone. Coffee/espresso taken 60 minutes after L-T4 ingestion had no significant effect on T4 intestinal absorption. It is prudent to remind patients that thyroid hormones should be separated from food and beverages (other than water), including coffee, by at least 30—60 minutes.^[6] Oral aluminum hydroxide, magnesium salts, calcium salts, calcium carbonate, and antacids, containing any of these electrolyte salts have been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with oral calcium supplements and aluminum hydroxide. This interaction may also occur with liothyronine. To be prudent and to minimize this interaction, administer liothyronine at least 4 hours before or after antacids or other drugs containing aluminum, magnesium, or calcium.^[5][8][9] Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, it may be prudent to administer oral liothyronine at least 4 hours before or after the ingestion of simethicone.^[5] Polysaccharide-iron complex and other oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.^[10] To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.^[5] Cholestyramine can bind T3 and T4 in the gastrointestinal tract, impairing absorption of both hormones.^[4] Colestipol may have similar effects on absorption. Other cholesterol-lowering agents might also interfere with thyroid absorption.^[11] At least 4—6 hours should be allowed between the administration of thyroid hormones and either cholestyramine or colestipol. Administration of thyroid hormones with sucralfate^[12] may result in a decreased bioavailability of liothyronine. The exact mechanism of this interaction is not known, but the agents should be separated in administration. Cation exchange resins like sodium polystyrene sulfonate (i.e., Kayexalate), can bind thyroid hormones in the GI tract and inhibit thyroid hormone absorption.^[5] Administer liothyronine at least 4 hours apart from cation exchange resins. The pharmacodynamics of the effects of thyroid agents in the diabetic patient are poorly understood. Close monitoring of blood glucose is necessary for individuals who use insulin or oral hypoglycemics whenever there is a change in thyroid treatment therapy. It may be necessary to adjust the dose of antidiabetic agents if liothyronine is added or discontinued.^[4] Ketamine should be administered cautiously to patients receiving thyroid hormone therapy.^[4] Concomitant use can cause marked hypertension and tachycardia. The administration of estrogen can increase circulating concentrations of serum thyroxine-binding globulin (TBg). Increased amounts of TBg reduce the clinical response to thyroid agents. Patients on thyroid replacement therapy may require larger doses of liothyronine if estrogens or estrogen-containing oral contraceptives are added to the drug regimen.^[4] Changes in TBg concentration should be taken into consideration when reviewing T4 and T3 laboratory values. Unbound (free) T3 should be measured, rather than total T3 (TT3). Due to the increased adrenergic effect of catecholamines caused by thyroid hormones, use of vasopressors may increase the risk of precipitating coronary insufficiency. Use caution when administering vasopressors with liothyronine.^[4] Concomitant use of sympathomimetics and thyroid hormones can enhance the effects of either drug on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Combined use of these agents may further increase this risk.^[4] Drugs that possess hepatic enzyme-inducing properties can increase the catabolism of levothyroxine and, thus, should be used cautiously with liothyronine.^[5] These include barbiturates, carbamazepine,^[13] hydantoins (i.e., fosphenytoin, phenytoin, or ethotoin)^[14] and rifamycins (e.g., rifabutin or rifampin).^[15] Clinicians should be alert for a decreased response to thyroid hormones if any of these agents are used during thyroid hormone therapy. The effects of indandione- or coumarin-derivative anticoagulants can be altered when thyroid agents are administered concomitantly. It has been shown that by accelerating the metabolic degradation of vitamin K-dependent clotting factors, hyperthyroidism augments the response to warfarin.^[16] It is possible that exogenously administered thyroid hormone also can augment the response to warfarin or dicumarol. INRs should be monitored carefully in patients receiving warfarin and liothyronine concomitantly and the dose of the anticoagulant should be adjusted as needed.^[4] The metabolism of corticosteroids and corticotropin (ACTH) are increased in patients with hyperthyroidism and decreased in patients with hypothyroidism. Therefore, caution should be taken when initiating, changing or discontinuing thyroid agents. Additionally, a decrease in thyroid binding globulin (TBg) concentrations have been observed following corticosteroid therapy and should be taken into consideration in the interpretation of T 4 and T 3 values, which guide thyroid treatment.^[4] Amiodarone has a complex effect on the metabolism of thyroid hormones and can alter thyroid function tests in many patients. Since approximately 37% of amiodarone (by weight) is iodine, maintenance doses of 200—600 mg of amiodarone/day result in ingestion of 75—225 mg/day of organic iodide, resulting in much higher total iodine stores in the body. In addition, amiodarone decreases T4 5'-deiodinase activity, which decreases the peripheral conversion of T4 to T3, leading to decreased serum T3. Serum T4 levels are usually normal but may be slightly increased. TSH concentrations usually increase during amiodarone therapy, but after 3 months of continuous administration, TSH concentrations often return to normal. However, amiodarone can cause hypothyroidism or hyperthyroidism, including life-threatening thyrotoxicosis. Therefore, patients receiving liothyronine and amiodarone should be monitored for changes in thyroid function; because of the slow elimination of amiodarone and its metabolites, abnormal thyroid function tests may persists for weeks or months after amiodarone drug discontinuation.^[5][17] Decreased digoxin clearance occurs with hypothyroidism; when corrected with thyroid hormone, clearance returns to normal. Hypothyroid patients may have an increased risk for digitalis toxicity.^[4] When thyroid hormone therapy is added, however, an increase in the digoxin dose may be necessary. Thyroid hormones may increase receptor sensitivity and enhance the effects of tricyclic antidepressants^[4] and related drugs (e.g., amoxapine,^[18] maprotiline.^[19]) Older literature describes a variety of responses when tricyclic antidepressants are used concomitantly with thyroid hormones. Thyroid hormones may accelerate the onset of action of tricyclic antidepressants; however, several case reports have described cardiovascular toxicity as a result of this drug combination; other reports describe no interaction. Although this drug combination appears to be safe, clinicians should be aware of the remote possibility of exaggerated cardiovascular side effects such as arrhythmias and CNS stimulation.^[4] Correction of hypothyroidism to the euthyroid state may precipitate certain drug interactions. For example, hypothyroidism causes decreased clearance of theophylline, which returns to normal in the euthyroid state. Theophylline dosage adjustments may be needed with thyroid hormone replacement.^[5] Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility,^[5] the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone are given to the patient. In addition, because liothyronine (T3) has more pronounced cardiovascular side effects when compared to levothyroxine (T4), the effects on beta-blockers may be more common in patients treated with liothyronine.^[4] Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption.^[8] Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric oral powder for solution).^[20] Thyroid hormones should be administered at least 2 hours before the administration of these ddI formulations to avoid an interaction. The delayed-release didanosine capsules (e.g., Videx® EC) do not contain a buffering agent and would not be expected to interact with thyroid hormones. Closely monitor the thyroid status of any patient taking thyroid hormones concurrently with indinavir. Hyperthyroidism was reported in a patient when indinavir was added to a stable levothyroxine dosing regimen. Indinavir inhibits UDP-glucuronosyl transferase, which may have decreased the metabolism of the thyroid hormone and may explain the increased thyroxine levels observed.^[21] Theoretically, similar interactions may occur between indinavir and other thyroid hormones, given that both T4 and T3 are metabolized to some degree via hepatic UDP-glucuronosyl transferase. The concomitant use of systemic tretinoin, ATRA and thyroid hormones should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension).^[22] Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.^[23][24] In order to increase thyroid uptake and optimize exposure of thyroid tissue to the radionucleotide sodium iodide I-131, patients must discontinue all medications and supplements that may interfere with iodide uptake into thyroid tissue prior to therapy with sodium iodide I-131. Although various protocols are used, a procedure guideline published by the Society of Nuclear Medicine in February 2002 recommends that all T4 thyroid hormones, such as levothyroxine, be discontinued 4—6 weeks and that all T3 thyroid hormones, such as liothyronine, be discontinued 2 weeks prior to sodium iodide I-131 therapy.^[25] The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy.^[26] To minimize potential for interactions, consider administering oral drugs with a narrow therapeutic index, such as liothyronine, at least 4 hours before colesevelam. There have been rare reports of elevated thyroid stimulating hormone (TSH) concentrations in patients who have received colesevelam coadministered with thyroid hormone replacement therapy.^[26] Excessive use of thyroid hormones with growth hormone (somatropin, rh-GH) may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to somatropin. Patients receiving concomitant therapy should be monitored closely to ensure appropriate therapeutic response to somatropin.^[5] Lithium therapy can result in goiter in up to 50% of patients, and subclinical or overt hypothyroidism in up to 20% of patients. Lithium decreases thyroid hormone synthesis and secretion leading to hypothyroidism after long-term use. Prevalence of hypothyroidism appears to be highest in women and in those patients over the age of 50, with a family history of hypothyroidism.^[27] Patients receiving thyroid hormones should be monitored for changes in thyroid function when lithium is either initiated or discontinued.^[5] Sevelamer could potentially decrease the oral absorption of other medications; the alteration can be clinically significant for drugs with a narrow therapeutic window such as the thyroid hormones.^[28] In one study of normal volunteers, the subjects (n=7) ingested orally levothyroxine sodium, either taken separately or co-administered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly (p <0.05) decreased the area under the serum thyroxine concentration curve. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.^[29] Administering levothyroxine 4 hours before or after sevelamer may minimize the potential for an interaction.^[28] Chromium could potentially decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n=7) ingested orally levothyroxine sodium, either taken separately or co-administered with chromium picolinate. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Chromium picolinate significantly (p <0.05) decreased the area under the serum thyroxine concentration curve. The authors concluded that patients should be advised to separate the time of ingestion of chromium from their thyroid hormone preparation.^[29] Administering levothyroxine 1 hours before or 3 hours after chromium picolinate ingestion, for example, should minimize the potential for an interaction. This list may not include all possible interactions.

Some possible side effects include: changes in appetite; changes in menstrual periods; diarrhea; hair loss; headache; trouble sleeping; weight loss. This list may not describe all possible side effects. Call your doctor for medical advice about side effects.

Monitor for signs and symptoms of hypothyroidism that could require an upward adjustment of the liothyronine dosage. Signs or symptoms of underdosage or hypothyroidism include constipation, cold intolerance, dry skin (xerosis) or hair, fatigue, impaired intellectual performance or other mental status changes (e.g., depression), deepening of voice, lethargy, weight gain, tongue enlargement, and, eventually, myxedema coma.

Adverse reactions to liothyronine are rare. Adverse reactions usually indicate inappropriate dosage of the hormone.^[2]

No well-documented evidence from the literature of true allergic or idiosyncratic reactions to thyroid hormone exist. Rare instances of allergic skin reactions such as urticaria (hives) or rash (unspecified) have been reported with the use of liothyronine tablets. Liothyronine injection or tablets can be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.^[2][30]

Transient partial alopecia may occur in children in the first few months of treatment, but normal hair growth usually recovers.^[2] Alopecia may be due to hyperthyroidism from therapeutic overdosage or to hypothyroidism from therapeutic underdosage.^[31]

Many of the signs and symptoms of thyroid hormone imbalance are subtle and insidious. Manifestations of liothyronine excessive dosage or hyperthyroidism include anorexia, diaphoresis, diarrhea, dyspnea, elevated hepatic enzymes, emotional lability, fatigue, fever, flushing, headache, heat intolerance, hyperthyroidism, appetite stimulation, infertility, irritability, insomnia, menstrual irregularity (e.g., amenorrhea), muscle weakness, muscle cramps, nausea, vomiting, nervousness or anxiety, tremor, and weight loss. The clinician should be alert to constellations of symptoms that gradually worsen over time.^[31] Thyrotoxicosis may result from massive overdosage producing symptoms that resemble thyroid storm.^[30] Reduce the liothyronine dose or temporarily discontinue liothyronine if signs and symptoms of overdosage appear. If appropriate, liothyronine may be reinstituted at a lower dosage.^[2]

Because the onset of liothyronine is faster than that of other thyroid preparations, some side effects may appear more rapidly, particularly with IV liothyronine use in myxedema. The most commonly reported adverse events associated with the use of liothyronine intravenous injection were cardiac arrhythmia (6% of patients) and sinus tachycardia (3% of patients); arrhythmia exacerbation may occur. Cardiopulmonary arrest (cardiac arrest), hypotension, and myocardial infarction occurred in approximately 2% of patients. Angina, congestive heart failure, twitching, and hypertension were reported in approximately 1% or fewer of patients.^[30] Also, too much thyroid hormone such as liothyronine may have adverse cardiovascular effects such as an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias. Symptoms may include palpitations, sinus tachycardia, arrhythmias, hypertension, heart failure, angina, myocardial infarction, and cardiac arrest.^[31] Peripheral edema may also occur. Patients with subclinical hyperthyroidism, either from excessive thyroid hormone replacement or other, may also be at an increased risk for atrial fibrillation. One study compared elderly patients (mean age 65 years) with subclinical hyperthyroidism to euthyroid subjects for 2 years; atrial fibrillation was initially recorded in 8 patients and 3 additional patients developed atrial fibrillation during follow-up; the data correspond to a total incidence of atrial fibrillation of 28% in subclinical hyperthyroidism patients compared to 10% in euthyroid subjects.^[32] Low initial doses of liothyronine are advised for patients where compromised integrity of the cardiovascular system, particularly the coronary arteries, is suspected or known such as patients with angina pectoris or the elderly. Also, reduce the dose in such patients if a euthyroid state can only be reached at the expense of an aggravation of the cardiovascular disease. Closely monitor infants for cardiac overload, arrhythmias, and aspiration from avid suckling during the first 2 weeks of thyroid hormone replacement.^[2][31]

In infants, excessive doses of thyroid hormone preparations such as liothyronine may produce craniosynostosis.^[2] Also, undertreatment may result in slowed reduced adult height, and overtreatment may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature (growth inhibition). Slipped capital femoral epiphysis has been reported in children receiving levothyroxine.^[31]

Pseudotumor cerebri has been reported in patients receiving thyroid hormone replacement therapy such as liothyronine.^[31] Symptoms such as headache, papilledema, and elevated opening pressures on lumbar puncture may occur within weeks of starting thyroid hormone replacement therapy and must be differentiated from brain metastases, if applicable.^[33][34]

Administration of too much liothyronine may lead to osteopenia and osteoporosis. Suppressed serum thyrotropin (TSH) concentrations by use of another thyroid hormone levothyroxine was associated with bone loss and the potential increased risk for osteopenia and the premature development of osteoporosis. Because estrogen plays a protective role against bone loss, this increased risk is thought to be relevant in postmenopausal women receiving prolonged thyroid therapy. In a meta-analysis that pooled study data on the effects of slight over treatment with levothyroxine on pre- and postmenopausal women, a significant reduction in bone mass was observed in the postmenopausal study groups. Pooled study data contained skeletal measurements of the distal forearm, femoral neck, and lumbar spines of postmenopausal women. For all postmenopausal women, a theoretical bone consisting of 11.3% distal forearm, 42% femoral neck, and 46.7% lumbar spine was constructed (n = 317 measurements). Data showed that a postmenopausal woman at an average age of 61.2 years and treated with levothyroxine for 9.93 years (leading to suppressed serum TSH) would have an excess loss of bone mass of 9.02%; corresponding to an excess annual loss of 0.91% after 9.93 years of levothyroxine treatment as compared to healthy postmenopausal women.^[35][36]

Phlebitis was reported in approximately 1% or fewer of liothyronine injection recipients.^[30]

This list may not include all possible adverse reactions or side effects. Call your health care provider immediately if you are experiencing any signs of an allergic reaction: skin rash, itching or hives, swelling of the face, lips, or tongue, blue tint to skin, chest tightness, pain, difficulty breathing, wheezing, dizziness, red, a swollen painful area/areas on the leg.

Liothyronine is classified in FDA pregnancy risk category A. Thyroid hormones undergo minimal placental transfer and human experience does not indicate adverse fetal effects; do not discontinue needed replacement during pregnancy.^[2] Also, hypothyroidism that is diagnosed during pregnancy should be promptly treated. Measure TSH during each trimester to gauge adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose, monitor thyroid function tests 6—8 weeks postpartum to assess for needed adjustments.

Thyroid hormones, like liothyronine, are generally compatible with breast-feeding; minimal amounts of thyroid hormones are excreted in breast milk.^[3] Thyroid hormones do not have a known tumorigenic potential and are not associated with serious adverse reactions in nursing infants. However, use caution when administering liothyronine to a nursing woman;^[2] changes in thyroid status in the post-partum period may require careful monitoring and maternal dosage adjustment. It should be noted that in general, adequate thyroid status is needed to maintain normal lactation, and there is no reason maternal replacement should be halted due to lactation alone. Levothyroxine is often the preferential drug to treat hypothyroidism and is considered compatible with breast feeding.^[3]

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

1. Bunevicius R, Kazanavicius G. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.9;340:424-9.
2. Cytomel (liothyronine sodium) package insert. Bristol, TN: King Pharmaceuticals, Inc.; 2004 March.
3. American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.
4. Cytomel® (liothyronine) package insert. St. Louis, MO: Jones Pharma Incorporated; 2001 Nov.
5. Levothroid (levothyroxine sodium tablet) package insert. Shenandoah, IA: Lloyd Pharmaceutical; 2011 June.
6. Benvenga S, Bartolone L, Pappalardo MA, et al. Altered intestinal absorption of L-thyroxine caused by coffee. Thyroid 2008;18:293-301.
7. Divi RL, Chang HC, Doerge Dr. Anti-thyroid isoflavones from soybean; isolation, characterization, and mechanisms of action. Biochem Pharmacol Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.7;54:1087—96.
8. Sperber AD, Liel Y. Evidence for interference with the intestinal absorption of levothyroxine sodium by aluminum hydroxide. Arch Int Med Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.2;152:183.
9. Singh N, Weisler SL, Hershman JM. The acute effect of calcium carbonate on the intestinal absorption of levothyroxine. Thyroid 2001;11:967—71.
10. Campbell N. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Int Med Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.2;117:1010.
11. Demke DM. Drug interaction between thyroxine and lovastatin. N Engl J Med Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.1;321:1341.
12. Havrankova J, Lahaie R. Levothyroxine binding by sucralfate. Ann Intern Med Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.2;117:445.
13. Tegretol® (carbamazepine) package insert. East Hanover, NJ. Novartis Pharmaceuticals; 2003 Sept.
14. Dilantin® Kapseals® (extended phenyotin sodium capsules, USP) package insert. Morris Plains, NJ: Parke Davis; Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.9 Aug.
15. Finch CK, Chrisman CR, Baciewicz AM, et al. Rifampin and rifabutin drug interactions: an update. Arch Intern Med 2002;162:985—92.
16. Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993;13:508—9.
17. Cordarone® (amiodarone) package insert. Philadelphia, PA: Wyeth Laboratories; 2007 Mar.
18. Amoxapine package insert. Corona, CA: Watson Laboratories, Inc.; 2007 Aug.
19. Ludiomil (maprotiline hydrochloride) package insert. Summit, NJ: Ciba-Geigy Corporation; 1996 Nov.
20. Videx® (didanosine chewable/dispersible buffered tablets and pediatric powder for oral solution) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2006 Jan.
21. Lanzafame M, Trevenzoli M, Faggian F, et al. Interaction between levothyroxine and indinavir in a patient with HIV infection. Infection 2002;30:54—5.
22. Vesanoid® (tretinoin) capsules package insert. Nutley, NJ: Roche Laboratories Inc.; 2004 Oct.
23. Griffin JP. A review of the literature on benign intracranial hypertension associated with medication. Adverse Drug React Toxicol Rev 1992;11:41—57. Review.
24. Lee AG. Pseudotumor cerebri after treatment with tetracycline and isotretinoin for acne. Cutis 1995;55:165—8. Review.
25. Meier DA, Brill DR, Becker DV, et al. Society of Nuclear Medicine procedure guideline for therapy of thyroid disease with iodide-131 (sodium iodide). January 26, 2006.
26. Welchol® (colesevelam) tablets package insert. Parsipanny, NJ: Daiiki Sankyo; 2006 Sept
27. Freeman MP, Freeman SA. Lithium: clinical considerations in internal medicine. Am J Med 2006;119:478—81.
28. Renagel® (sevelamer) package insert. Cambridge, MA: Genzyme Corporation; 2004 Feb.
29. Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid 2007;17:763—5.
30. Triostat (liothyronine injection) package insert. Rochester, MI: JHP Pharmaceuticals, LLC; 2009 Feb.
31. Synthroid (levothyroxine) tablets. North Chicago, IL: Abbott Pharmaceuticals; 2012 Sep.
32. Tenerz A, Forberg R, Jansson R. Is a more active attitude warranted in patients with subclinical thyrotoxicosis? J Int Med 1990;228:229-233.
33. Van Dop C, Conte FA, Koch TK, et al. Pseudotumor cerebri associated with initiation of levothyroxine therapy for juvenile hypothyroidism. N Engl J Med 1983;308: 1076-80.
34. Panza N, DeRosa M, Lombardi G, et al. Pseudotumor cerebri and thyroid-replacement therapy in patients affected by differentiated thyroid carcinoma. J Endocrinol Invest 1985;8:357-358.
35. Samuels MH. Subclinical thyroid disease in the elderly. Thyroid 1998;8:803-13.
36. Faber J, Galloe AM. Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis. Eur J Endocrinol 1994;130:350-6.