Liothyronine Sodium (liothyronine sodium)

The oral liothyronine dosage regimen for hypothyroidism or pituitary TSH suppression is dependent upon a variety of factors including patient age, body weight, cardiovascular status, concomitant medical conditions and medications, concurrently administered food, and nature of the treated condition. Dosage of oral liothyronine should be individualized and dosage adjustments undertaken based on periodic assessment of clinical response and laboratory parameters.

If an adequate oral liothyronine replacement dose is administered but clinical and laboratory evidence of hypothyroidism persist, the clinician should evaluate the patient for inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

Liothyronine sodium is administered orally or by IV injection. Liothyronine injection should not be administered intramuscularly or subcutaneously.

Liothyronine tablets should be stored between 15-30degreesC. Liothyronine for injection should be stored under refrigeration (2-8degreesC).

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Agents That Affect Iodide/Radioactive Iodide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(2) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(3)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1)

Agents That Affect Iodide/Sodium Iodide I 131

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1,2)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1,2)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1,2) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(3) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(4)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1,2)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Thyroid Preparations/Carbimazole; Methimazole

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Methimazole can affect the therapeutic response to thyroid hormone therapy. It decreases thyroid hormone secretion. Thyroid hormone therapy can antagonize the pharmacologic effects of methimazole by supplying an exogenous source of thyroid hormone. Carbimazole is a prodrug of methimazole.(1)

CLINICAL EFFECTS: Concurrent use of carbimazole or methimazole and thyroid hormones may result in opposing effects.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of carbimazole or methimazole and thyroid hormones should be avoided.

DISCUSSION: The 2016 American Thyroid Association guidelines recommended avoiding the concurrent use of methimazole and thyroid preparations for "block and replace" therapy to make a patient euthyroid. Meta-analyses have shown that a higher prevalence of adverse events occurs with block-and-replace regimens than dose titration.(2) The 2018 European Thyroid Association guidelines state that methimazole (30 mg) may be given combined with levothyroxine supplement ion for block-and-replace therapy to avoid drug-induced hypothyroidism but methimazole dose titration is the preferred therapy.(3)

Thyroid Preparations/Estrogens

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Estrogens increase thyroxine-binding globulin (TBG) levels by increasing its biosynthesis and decreasing its clearance.(1) Hypothyroid patients who start estrogens may be unable to compensate for this increase and may have decreased serum free T4 (FT4) concentrations and increased TSH.(1,2)

CLINICAL EFFECTS: The coadministration of thyroid preparations and estrogens may result in decreased levels and clinical effects of thyroid hormones.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and who start or stop estrogens should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased.(1-4)

DISCUSSION: In a prospective observational study, 25 post-menopausal women with hypothyroidism on stable levothyroxine therapy for at least 9 months started on estrogen replacement therapy. After 12 weeks, mean serum FT4 levels decreased significantly from 1.7 +/- 0.4 ng/dL to 1.4 +/-0.3 mg/dL and TSH increased significantly from 0.9 +/-1.1 to 3.2 +/- 3.1 milli-units/L.(1)

Thyroid Preparations/Sertraline

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism by which sertraline lowers serum thyroid hormone concentrations is uncertain. One reported case in which sertraline caused a low serum total thyroxine concentration is believed to be caused by sertraline increasing the clearance of the thyroxine.(1)

CLINICAL EFFECTS: The coadministration of thyroid preparations and sertraline may result in decreased levels and clinical effects of thyroid hormones.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients taking thyroid preparations and sertraline should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased.

DISCUSSION: In a case report of 9 levothyroxine treated patients with hypothyroidism, who were treated with sertraline, all were found to have elevated serum thyrotropin concentrations. Elevated thyrotropin levels are indicative of a decrease in the efficacy of levothyroxine. The dose of levothyroxine was increased for all patients. Required dosage adjustments ranged from 11% to 50%.(1) In a study, patients with major depression and hypothyroidism on adequate levothyroxine therapy were treated with either fluoxetine or sertraline. The results of this study showed no change in thyroid levels among hypothyroid patients on levothyroxine therapy who were treated with either fluoxetine or sertraline.(2)

Thyroid/Selected Anticoagulants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unknown. However, thyroid hormones may influence concentrations of vitamin K-dependent clotting factors.

CLINICAL EFFECTS: Concurrent use of vitamin K antagonists and thyroid hormones may increase the risk for bleeding. Hypothyroidism may increase the oral anticoagulant requirements. Administration of thyroid hormones or hyperthyroidism may decrease oral anticoagulant requirements.

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Monitor prothrombin activity and adjust the anticoagulant dosage accordingly during initiation of warfarin therapy in patients receiving thyroid replacement therapy, during the initiation or titration of thyroid replacement therapy in patients receiving warfarin, or if any changes in thyroid function occur. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: Any change in thyroid status in patients stabilized on warfarin may necessitate a change in warfarin dosage requirements. Initiation of thyroid replacement therapy in patients stabilized on warfarin may result in increases in the effects of warfarin. A decrease in the dose of warfarin usually becomes necessary within one to four weeks after starting therapy with thyroid compounds. Warfarin therapy should be initiated in low doses in patients who are hyperthyroid. In a 16 year population based nested matched case control study, 10,532 hospitalizations for hemorrhage were evaluated and matched to 40,595 controls. The primary analysis showed no increase in risk of hemorrhage in older patients on warfarin initiated on levothyroxine in previous 30 days (OR 1.11, 95% CI 0.67-1.86). When patients were matched up to 90 days prior to the hemorrhage event, there was no significant association with levothyroxine 31-60 days prior to index date (OR 0.75 95% CI 0.26-2.25) or 61-90 days prior to index date (OR 0.67 95% CI 0.15-3.01). A retrospective, self-controlled study of 102 patients on chronic warfarin therapy were included if the patient had INR results 90 days before and after starting levothyroxine. The mean warfarin dose/INR ratio in the pre-period and post-period had no significant change (p=0.825). In patients who achieved euthyroid during post-period, warfarin dose/INR ratio was numerically lower in the post-period but not statistically significant (13.42 versus 12.7, respectively; p=0.338). In patients initiated on levothyroxine doses greater than 50 mcg, pre-period and post-period warfarin dose/INR ratio also had no significant difference (p>0.2).

*Uncorrected adrenal insufficiency.

*Untreated thyrotoxicosis.

*Hypersensitivity to any of the active or extraneous ingredients of the formulation.

*Concomitant use of IV liothyronine and artificial patient rewarming.

• Thyrotoxicosis crisis

• Primary adrenocortical insufficiency
• Thyrotoxicosis

• Coronary artery disease
• Diabetes mellitus
• Hypertension

The most common adverse reactions of oral liothyronine therapy are primarily hyperthyroidism-related due to therapeutic overdosage and include arrhythmias, myocardial infarction, dyspnea, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash. Hypersensitivity reactions (e.g., urticaria, pruritus, skin rash, angioedema, GI symptoms, fever, arthralgia, serum sickness, wheezing) to inactive ingredients in oral thyroid hormone products have been reported.

The most common adverse reactions of IV liothyronine therapy include arrhythmia (6%) and tachycardia (3%). Approximately 2% of patients experience cardiopulmonary arrest, hypotension, and myocardial infarction. Angina, congestive heart failure, fever, hypertension, phlebitis, and twitching have been reported in approximately <=1% of patients.

Less Frequent

• Osteopenia

Rare or Very Rare

• Abnormal hepatic function tests
• Acute myocardial infarction
• Angina
• Angioedema
• Cardiac arrest
• Cardiac arrhythmia
• Dyspnea
• Heart failure
• Idiopathic intracranial hypertension
• Mood changes
• Seizure disorder
• Skin rash
• Slipped capital epiphyses
• Tachycardia
• Urticaria

More Frequent

• Female infertility

Less Frequent

• Hypertension
• Weight loss

Rare or Very Rare

• Abdominal pain with cramps
• Alopecia
• Chest pain
• Diarrhea
• Fatigue
• Fever
• Flushing
• Headache disorder
• Heat intolerance
• Hyperhidrosis
• Increased appetite
• Increased pulse rate
• Insomnia
• Irregular menstrual periods
• Irritability
• Menstrual disorder
• Muscle spasm
• Muscle weakness
• Nervousness
• Palpitations
• Symptoms of anxiety
• Tremor
• Vomiting

No enhanced messaging available.

In pediatric patients with congenital hypothyroidism, oral thyroid hormone therapy should be initiated immediately upon diagnosis in order to prevent adverse effects on intellectual development, growth, and maturation; therapy is generally lifelong in these patients. During the first 2 weeks of thyroid agent therapy, infants should be closely monitored for cardiac overload, arrhythmias, and aspiration resulting from avid suckling.

Pediatric patients with congenital or acquired hypothyroidism should be monitored closely to avoid undertreatment or overtreatment. Undertreatment may result in negative effects on intellectual development and growth while overtreatment may result in craniosynostosis in infants and accelerate the aging of bones, resulting in premature epiphyseal closure and compromised adult stature.

In pediatric patients with acquired hypothyroidism administered oral thyroid hormone therapy, a period of catch-up growth may occur, which may be adequate in some cases to achieve normal adult height. In children with severe or long-standing hypothyroidism, catch-up growth may not be adequate to achieve normal adult height.

If a diagnosis of permanent hypothyroidism has not been established in a pediatric patient, oral thyroid hormone therapy should be discontinued for a trial period, but only after the patient is >=3 years of age. Clinicians should obtain various laboratory tests (e.g., serum TSH, T4, T3) at the end of the trial period and use results to guide diagnosis and treatment.

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving oral thyroid agent therapy.

The efficacy and safety of IV liothyronine have not been established in pediatric patients.

The required oral liothyronine dosage may increase during pregnancy in patients with pre-existing hypothyroidism. For patients with serum TSH above the normal trimester-specific range, clinicians should increase the liothyronine dosage and measure TSH every 4 weeks until a stable dose is achieved and serum TSH is within the normal trimester-specific range.

The oral liothyronine dosage should be reduced to pre-pregnancy levels immediately after delivery. Serum TSH levels should be measured 4 to 8 weeks postpartum to ensure an appropriate liothyronine dosage.

In pregnant women, data from postmarketing studies have not reported increased rates of fetal malformations, miscarriages, or other adverse maternal or fetal outcomes with liothyronine therapy. No animal studies evaluating use of liothyronine during pregnancy have been conducted.

Untreated hypothyroidism during pregnancy is associated with risks to the mother and fetus; liothyronine therapy should not be discontinued during pregnancy. If hypothyroidism is diagnosed during pregnancy, clinicians should promptly treat the condition. Thyroid stimulating hormone (TSH) levels may increase during pregnancy and should be monitored, with liothyronine dosage adjusted as appropriate. The liothyronine dose should be returned to the pre-pregnancy dose immediately after delivery since postpartum TSH levels are similar to preconception values.

Liothyronine is present in human milk. There is insufficient information available to determine the effects of the drug on the breastfeeding infant or milk production. The developmental and health benefits of breastfeeding should be considered along with the clinical need for liothyronine and any potential adverse effects on the breastfed infant or from the underlying maternal condition.

Geriatric patients should be initiated on less than the full replacement dose of oral liothyronine due to the increased prevalence of cardiovascular disease in this patient population.

Hypothyroidism: in elderly patients, start with 5 mcg once daily and increase by 5 mcg increments at the recommended intervals.

Liothyronine oral therapy should be initiated at less than the full replacement dose in geriatric patients due to the increased prevalence of cardiovascular disease in this patient population. The most common arrhythmia observed among geriatric patients with thyroid hormone overtreatment is atrial fibrillation.

Clinical studies of IV liothyronine therapy did not include a sufficient number of patients >=65 years of age to determine whether they respond differently from younger patients; however, other clinical experience has not reported differences in response between geriatric and younger patients. In geriatric patients, the dose of IV liothyronine should be initiated at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this patient population.

Since IV liothyronine is excreted by the kidneys, clinicians should monitor renal function in geriatric patients.