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  • CLASSES

    Antidepressant Augmentation Agents
    Thyroid Agents

    BOXED WARNING

    Obesity treatment

    Liothyronine should not be used for obesity treatment or weight loss. In euthyroid patients, thyroid hormone doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious manifestations of toxicity and hyperthyroidism, especially if used with anorexic agents such as the sympathomimetic amines.[46855] [54444]

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral synthetic form of the thyroid hormone triiodothyronine (T3); faster onset of action (no need to peripherally convert T4 to T3) vs. levothyroxine
    Used for myxedema coma in combination with levothyroxine; monitor for cardiostimulatory effects
    Levothyroxine (T4) alone is preferred for routine therapy of hypothyroidism; however, partial replacement with T3 is used in selected patients after T4 dose stabilization

    COMMON BRAND NAMES

    Cytomel, Triostat

    HOW SUPPLIED

    Cytomel/Liothyronine/Liothyronine Sodium Oral Tab: 5mcg, 25mcg, 50mcg
    Liothyronine/Liothyronine Sodium/Triostat Intravenous Inj Sol: 1mL, 10mcg

    DOSAGE & INDICATIONS

    For the treatment of hypothyroidism of any etiology, except during the recovery phase of subacute thyroiditis; used as a replacement in primary (thyroidal), secondary (pituitary), tertiary (hypothalamic), congenital (cretinism), or acquired hypothyroidism.
    For the treatment of hypothyroidism.
    Oral dosage
    Adults

    Initially, 25 mcg PO once daily. Increase dosage by 25 mcg/day or less every 1 to 2 weeks as required. Maintenance dose is usually 25 to 75 mcg PO once daily. Use lower initial doses and slower titration in debilitated patients or those with known cardiovascular disease: Initially, 5 mcg PO once daily; with a suggested titration schedule of 5 mcg/day every 1 to 2 weeks as required.[46855] Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism. There is insufficient evidence to suggest that liothyronine-only therapy is a safe or advantageous treatment for hypothyroidism in the general population, including in hypothyroid patients with obesity and dyslipidemia.[60310]

    Geriatric Adults

    Initially, 5 mcg PO once daily with a suggested titration schedule of 5 mcg/day every 1 or 2 weeks as required. Usual maintenance dose is 25 to 75 mcg PO once daily.[46855] Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism. There is insufficient evidence to suggest that liothyronine-only therapy is a safe or advantageous treatment for hypothyroidism in the general population, including in hypothyroid patients with obesity and dyslipidemia.[60310]

    Children and Adolescents

    Initially, 5 mcg PO once daily with a suggested titration schedule of 5 mcg/day every 3 to 4 days until the desired response is achieved. Usual maintenance dose is 25 to 75 mcg PO once daily. In patients at risk of hyperactivity, start at one-fourth of the recommended full replacement dose, and increase on a weekly basis by this same increment until the desired response is attained.[46855] Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism. There is insufficient evidence to suggest that liothyronine-only therapy is a safe or advantageous treatment of hypothyroidism in the general population, including in hypothyroid patients with obesity and dyslipidemia.[60310]

    For congenital hypothyroidism (cretinism).
    Oral dosage
    Neonates and Infants

    Initially, 5 mcg PO once daily. Increase dose in 5 mcg increments every 3 to 4 days as required. Infants a few months old may require maintenance doses of 20 mcg PO once daily. In newborns (0 to 3 months) at risk of cardiac failure, consider a lower starting dose. Increase the dose as needed based on clinical and laboratory response. At 1 year of age, a maintenance dose of 50 mcg PO once daily may be required.[46855] Treatment should be initiated immediately upon diagnosis and continued for life unless re-evaluation at approximately 3 years of age suggests a trial discontinuation of treatment at that time.[46855] The American Academy of Pediatrics and other clinical guidelines prefer levothyroxine over liothyronine for treatment.[22902] [60310]

    Children and Adolescents

    Initially, 5 mcg PO once daily. Increase dose in 5 mcg increments every 3 to 4 days as required; at 1 year of age, a maintenance dose of 50 mcg PO once daily may be required. Children older than 3 years of age may require the usual adult maintenance dose (i.e., 25 to 75 mcg/day PO).[46855] Initiate treatment immediately upon diagnosis and continue for life unless transient hypothyroidism is suspected, then therapy may be interrupted for 2 to 8 weeks after the age of 3 years for assessment. Cessation of therapy may be justified in patients who have maintained a normal TSH during those 2 to 8 weeks. In patients at risk of hyperactivity, start at one-fourth the recommended full replacement dose, and increase on a weekly basis by this same increment until the desired replacement dose is attained.[46855] The American Academy of Pediatrics and other clinical guidelines prefer levothyroxine over liothyronine for treatment.[22902] [60310]

    Adults

    The usual adult maintenance dose is 25 to 75 mcg/day PO. If treatment is continued into adult age, then treatment is continued for life.

    For the treatment of myxedema coma.
    Intravenous dosage
    Adults

    Initially, 25 mcg to 50 mcg IV is recommended. Use a lower initial dose of 10 mcg to 20 mcg IV in adults with known or suspected cardiovascular disease. Administer subsequent doses based on continuous monitoring of the patient's clinical condition and response to therapy. Normally at least 4 hours and no more than 12 hours should elapse between doses to assess therapeutic response and avoid fluctuations in hormone levels. Use caution when adjusting dose due to the potential for precipitating cardiovascular events in susceptible patients. Administration of at least 65 mcg/day IV, when used as monotherapy, has been associated with lower mortality. MAX: There is limited experience with a total daily dose of more than 100 mcg/day IV.[54444] IMPORTANT:Simultaneous administration of glucocorticoids is required at or before the start of treatment to prevent acute adrenocortical insufficiency and shock. CONVERSION TO ORAL TREATMENT: Resume oral therapy when the patient is clinically stable and able to take oral medications. When switching to oral therapy with levothyroxine after the patient is stabilized, discontinue liothyronine IV gradually as there is a delay in the onset of levothyroxine activity.[54444] GUIDELINES: Per guidelines, levothyroxine IV remains the therapy of choice. Conversion of T4 to T3 may be decreased in some patients with myxedema coma, and clinicians may consider liothyronine IV in addition to levothyroxine IV for selected patients. High doses should be avoided due to an association of high serum T3 with mortality in these patients. Guidelines recommend a liothyronine 5 to 20 mcg IV loading dose, followed by 2.5 to 10 mcg IV every 8 hours, with lower doses chosen for smaller, older patients and those with a history of coronary artery disease or arrhythmia. Therapy can continue until the patient is clearly recovering (e.g., until the patient regains consciousness and clinical parameters have improved).

    For diagnostic use in thyroid suppression testing (T3 suppression test) to differentiate a suspected mild hyperthyroidism diagnosis or thyroid gland autonomy.
    Oral dosage
    Adults

    75 mcg to 100 mcg PO once daily for 7 days. Radioactive iodine uptake is determined before and after the 7-day administration of liothyronine. If thyroid function is under normal control, the radioiodine uptake will drop significantly after treatment. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.

    As an adjunct to surgery and radioiodine (RAI) therapy in the management of well-differentiated thyroid cancer.
    Oral dosage
    Adults

    The dose should target TSH levels within the desired therapeutic range. This may require higher doses of thyroid hormone than those typically used for other indications, depending on the target level for TSH suppression. LIMITATION OF USE: Liothyronine is not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients as there are no clinical benefits and overtreatment with may induce hyperthyroidism. GUIDELINES: Per guidelines, levothyroxine is the preferred agent, but liothyronine may be used for short-term replacement of levothyroxine when necessary; thyroid hormone must be withdrawn for several weeks prior to RAI remnant ablation/treatment or diagnostic scanning.

    For use as triiodothyronine replacement therapy for organ preservation† of heart transplantation donors prior to procurement.
    Intravenous dosage
    Heart donors

    Initial dose of 2 mcg IV repeated hourly as needed according to response to treatment and condition of donor until excision of heart. Max: 0.6 mcg/kg IV administered an average of 139 minutes prior to organ procurement.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Liothyronine has a narrow therapeutic index; dosage must be individualized.

    Adults

    There is limited clinical experience with more than 100 mcg/day PO or IV.

    Geriatric

    There is limited clinical experience with more than 100 mcg/day PO or IV.

    Adolescents

    Adolescents in whom growth and puberty are complete: There is limited clinical experience with more than 100 mcg/day PO or IV.

    Children

    Oral dosage must be individualized to age, weight, growth, and clinical status; if more than 3 years of age, adult dosages may be required (adult usual Max: 100 mcg/day PO). There is limited experience with IV use; safety and efficacy of IV use in pediatric patients have not been established.

    Infants

    Individualize dosage.

    Neonates

    Individualize dosage.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No specific dosage adjustments are needed for patients with hepatic impairment; dosing is individualized to achieve therapeutic goals.

    Renal Impairment

    Liothyronine is known to be substantially excreted by the kidney, and the risk of toxic reactions may be increased in patients with renal impairment. Care should be used during initial dose selection. Dosing is individualized to achieve therapeutic goals.

    ADMINISTRATION

    Oral Administration

    Administer orally on an empty stomach with a glass of water at least 30 to 60 minutes before breakfast. Administer apart from medications known to decrease oral absorption.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Liothyronine sodium injection is for intravenous administration only. Do not give intramuscularly or subcutaneously.
    No dilution is necessary; give by direct intravenous injection.
    Careful cardiac monitoring (e.g., heart rate, blood pressure) is recommended during intravenous use.

    STORAGE

    Cytomel:
    - Store at room temperature (between 59 to 86 degrees F)
    Triostat:
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Liothyronine is contraindicated in any patient with a known hypersensitivity to liothyronine or any of its excipients; however, there is no well-documented evidence in the literature of true allergic or idiosyncratic reactions to thyroid hormone. Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. Liothyronine injection and tablets are synthetically derived and may be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.

    Thyrotoxicosis

    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.

    Adrenal insufficiency

    Liothyronine is contraindicated for use in patients with diagnosed but untreated adrenal insufficiency. Initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy may precipitate an acute adrenal crisis in patients with adrenal insufficiency due to an increase in the body's demand for adrenal hormones. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with liothyronine.

    Hypopituitarism

    Serum TSH is not a reliable measure of liothyronine dose adequacy in patients with secondary (hypopituitarism) hypothyroidism or tertiary (hypothalamic) hypothyroidism and should not be used to monitor therapy. An inappropriate TSH may be seen if hypothyroidism is caused by TSH deficiency (e.g. secondary hypothyroidism in patients with panhypopituitarism), and the TSH will not normalize with thyroid treatment. Use the serum T3 level to monitor for adequacy of therapy in this patient population.

    Acute myocardial infarction, angina, cardiac arrhythmias, cardiac disease, coronary artery disease, heart failure, hypertension, myocardial infarction, surgery

    Many authorities recommend lower initial dosages and slower titration of thyroid hormones in patients with cardiac disease and coronary artery disease (CAD). Thyroid hormones such as liothyronine should be used with great caution in patients where the integrity of the cardiovascular system is suspect. All liothyronine dosage formulations are cardiostimulatory and should be used with great caution in patients with angina pectoris, uncontrolled hypertension, cardiac arrhythmias, CAD, a previous history of myocardial infarction, or current acute myocardial infarction. If adverse cardiac symptoms develop or worsen during treatment, reduce or withhold liothyronine and cautiously restart at a lower dose. Over-treatment with liothyronine 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 vasopressors or sympathomimetic agents may precipitate coronary insufficiency and associated symptoms, particularly in myxedematous patients or those with CAD. Fluid therapy should be administered with great care to prevent cardiac decompensation. In patients with compromised cardiac function, use thyroid hormones in conjunction with careful cardiac monitoring. A lower starting dose is recommended in adult and pediatric patients at risk for heart failure or sensitive to thyroid stimulation. Careful monitoring is also recommended during surgery, as some anesthetic agents may induce changes in heart rate or blood pressure when administered with thyroid hormones.[54444] [46855] [60310]

    Diabetes mellitus

    Liothyronine therapy can worsen glycemic control in patients with diabetes mellitus, and result in increased antidiabetic agent or insulin requirements. The effects seen are poorly understood and depend upon a variety of factors such as dose and type of thyroid preparations and endocrine status of the patient. Blood glucose should be monitored closely during concomitant therapy, particularly during initiation, dose adjustments, or discontinuation of therapy.

    Obesity treatment

    Liothyronine should not be used for obesity treatment or weight loss. In euthyroid patients, thyroid hormone doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious manifestations of toxicity and hyperthyroidism, especially if used with anorexic agents such as the sympathomimetic amines.[46855] [54444]

    Hyponatremia, hypothermia, myxedema, water intoxication

    Patients with myxedema coma require immediate and intensive treatment. Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism and may result in unpredictable absorption of oral thyroid hormone from the gastrointestinal tract. Initial thyroid hormone replacement for myxedema coma should be given intravenously. The use of oral thyroid hormone drug products is not recommended.[46855] [60310] Although patients with myxedema coma often suffer from hypothermia, artificial rewarming is contraindicated with concomitant use of intravenous liothyronine. Peripheral vasodilation produced by artificial 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. Patients with myxedema coma show increased sensitivity to thyroid agents; initiate therapy with low doses of intravenous liothyronine and increase gradually. Simultaneous administration of glucocorticoids is required for these patients. Patients with pituitary myxedema should receive such adrenocortical hormone replacement therapy at or before the start of treatment to prevent acute adrenocortical insufficiency and shock. Hyponatremia is frequently present in myxedema coma, but usually resolves without specific therapy as the metabolic status of the patient improves with thyroid treatment. Use great care with fluid therapy to prevent cardiac decompensation; some patients with myxedema have inappropriate secretion of ADH and are susceptible to water intoxication. In some patients, respiratory depression has been a significant factor in the development or persistence of the comatose state. Decreased oxygen saturation and elevated CO2 levels respond quickly to artificial respiration.[54444]

    Renal failure, renal impairment

    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 during initial dosage selection for these patients; lower initial dosages and slower titration may be needed, particularly in the elderly.

    Osteopenia

    Long-term use of thyroid hormones, like liothyronine, has been associated with increased bone resorption and decreased bone mineral density (osteopenia), particularly in postmenopausal females on greater than replacement doses or in any women receiving suppressive doses. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase, and suppressed serum parathyroid hormone levels. Patients should be given the minimum dose necessary for desired clinical and biochemical response to limit risks for osteopenia.

    Intramuscular administration, subcutaneous administration

    Intramuscular administration or subcutaneous administration of liothyronine injection is not recommended. Administration of liothyronine injection is by the intravenous route only.

    Geriatric

    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. Atrial fibrillation is the most common of the arrhythmias observed with thyroid hormone overtreatment in the elderly. Lower initial dosages and slower titration are recommended; individualize the dosage. According to the Beers Criteria, there may be concerns regarding adverse cardiac effects with liothyronine use; when possible, use the thyroid replacement medication of choice, levothyroxine, which is considered safer for chronic therapy in the geriatric patient. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); assessment of thyroid function (e.g., TSH, serum T4 or T3) should occur before initiating thyroid medication and periodically thereafter, including assessment of thyroid function tests if new signs and symptoms of hypothyroidism or hyperthyroidism develop. Initiate thyroid supplementation at low doses and increase gradually to avoid precipitating cardiac failure or adrenal crisis. Because there are many clinically significant medication interactions, re-evaluation of medication doses should occur as clinically indicated.

    Pregnancy

    The clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones such as liothyronine are administered during pregnancy. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy. Thyroid hormones undergo minimal placental transfer. Hypothyroidism that is diagnosed during pregnancy should be promptly treated.[46855] [54444] During pregnancy, T4 is thought to be crucial for fetal brain development, and guidelines recommend that levothyroxine be the preferred drug vs. liothyronine for treatment in the pregnant patient. Measure TSH and free-T4 as soon as pregnancy is confirmed and, at a minimum, during each trimester to gauge the adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. For patients with serum TSH above the normal trimester-specific range, increase the dose of thyroid hormone and measure TSH every 4 weeks until a stable dose is reached and serum TSH is within the normal trimester-specific range. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose; monitor thyroid function tests 4 to 8 weeks postpartum to assess for needed adjustments.[46855] [54444]

    Breast-feeding

    In general, thyroid hormones are compatible with breast-feeding. Changes in thyroid status in the post-partum period may require careful monitoring and maternal dosage adjustment. 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. Limited published studies report that liothyronine is present in human milk. There is insufficient information to determine the effects of liothyronine on the breastfed infant and no available information on the effects of liothyronine on milk production. However, thyroid hormones do not have a known tumorigenic potential and are not associated with reports of serious adverse reactions in nursing infants.[46855] [54444] Levothyroxine (T4) is often the preferential drug to treat hypothyroidism in most patients and is considered compatible with breast-feeding.[27500] [60310] The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breastfed infant from liothyronine or the underlying maternal condition.[46855] [54444]

    Infertility

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

    Epiphyseal closure, hyperthyroidism

    Guidelines recommend levothyroxine (T4) as the generally the preferred treatment for hypothyroidism in all pediatric and adult patients. [60310] However, there are case reports of patients whose TSH values could only be normalized with a combination of both T4 and T3 (liothyronine). Therefore, treatment must be individualized. Closely monitor all patients to avoid undertreatment or overtreatment, which may produce hyperthyroidism or iatrogenic thyrotoxicosis.[60310] The management of hypothyroidism in pediatric patients is similar to adults, but there are unique differences based on the requirement of normal thyroid function for neurocognitive development as well as growth and development. There are increased weight-based requirements for thyroid hormone replacement in children and adolescents compared to adults. As the child advances through the pediatric age into adulthood thyroid hormone replacement doses decrease, with a transition to the average adult dose once endocrine maturation is complete.[60310] Careful monitoring for growth, weight, epiphyseal closure or maturation, and clinical status are important in all pediatric patients. In patients with congenital hypothyroidism, closely monitor infants during the first 2 weeks of thyroid hormone therapy for cardiac overload, arrhythmias, and aspiration from avid suckling.[46855] Undertreatment may have deleterious effects on intellectual development and linear growth. Overtreatment is associated with craniosynostosis in infants, may adversely affect the tempo of brain maturation, and may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature. In children with acquired hypothyroidism, undertreatment may result in poor school performance due to impaired concentration and slowed mentation and in reduced adult height. Treated children may manifest a period of catch-up growth, which may be adequate in some cases to normalize adult height. In children with severe or prolonged hypothyroidism, catch-up growth may not be adequate to normalize adult height.[46855] Safety and efficacy of intravenous (IV) liothyronine therapy in children, infants, or neonates have not been established; there is limited experience with parenteral use in this population.[54444]

    ADVERSE REACTIONS

    Severe

    arrhythmia exacerbation / Early / 1.0-10.0
    cardiac arrest / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    craniosynostosis / Delayed / Incidence not known
    epiphyseal closure / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    serum sickness / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    sinus tachycardia / Rapid / 1.0-10.0
    phlebitis / Rapid / 0-1.0
    elevated hepatic enzymes / Delayed / Incidence not known
    hyperthyroidism / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    thyrotoxicosis / Delayed / Incidence not known
    heat intolerance / Early / Incidence not known
    dyspnea / Early / Incidence not known
    angina / Early / Incidence not known
    hypertension / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    growth inhibition / Delayed / Incidence not known
    pseudotumor cerebri / Delayed / Incidence not known
    osteoporosis / Delayed / Incidence not known
    osteopenia / Delayed / Incidence not known
    wheezing / Rapid / Incidence not known

    Mild

    alopecia / Delayed / Incidence not known
    amenorrhea / Delayed / Incidence not known
    emotional lability / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    fever / Early / Incidence not known
    nausea / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    weakness / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    abdominal pain / Early / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    irritability / Delayed / Incidence not known
    fatigue / Early / Incidence not known
    headache / Early / Incidence not known
    vomiting / Early / Incidence not known
    flushing / Rapid / Incidence not known
    hyperactivity / Early / Incidence not known
    insomnia / Early / Incidence not known
    tremor / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    rash / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known

    DRUG INTERACTIONS

    Acarbose: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Acetaminophen; Butalbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Acetaminophen; Butalbital; Caffeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Acetohexamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Albiglutide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Alogliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Alogliptin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Alogliptin; Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Alpha-glucosidase Inhibitors: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Aluminum Hydroxide: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Amiodarone: (Moderate) 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 levothyroxine 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.
    Amobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Amoxapine: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of amoxapine. 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.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Asparaginase Erwinia chrysanthemi: (Moderate) Some hypothyroid patients receiving asparaginase may require reduced doses of thyroid hormone. Other patients may remain euthyroid during combined treatment. MonitorTSH levels and monitor for symptoms of hyperthyroidism; a free-T4 concentration may be useful to assess euthyroidism. Asparaginase may decrease the serum TBG (thyroxine-binding globulin) concentration. Decreased amounts of TBG may result in an increased clinical response to thyroid hormones.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Aspirin, ASA; Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Azelastine; Fluticasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Barbiturates: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Beclomethasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Beta-agonists: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Beta-blockers: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, 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 is given to the patient.
    Betamethasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Budesonide: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Budesonide; Formoterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Butabarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Calcium Acetate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium Carbonate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium Carbonate; Risedronate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium Carbonate; Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium Chloride: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium Gluconate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Calcium; Vitamin D: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Canagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Canagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Carbamazepine: (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
    Chlorpropamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Cholestyramine: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of cholestyramine. Cholestyramine and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Chromium: (Moderate) Advise patients to separate chromium supplement ingestion from taking their oral thyroid hormone. For example, taking oral thyroid hormones 1 hours before or 3 hours after chromium picolinate ingestion should minimize an interaction. Chromium could potentially decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested 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 decreased the serum thyroxine concentrations. (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Ciclesonide: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Cocaine: (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
    Colesevelam: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Colestipol: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colestipol. Colestipol and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Corticosteroids: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Corticotropin, ACTH: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Cortisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Dapagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued
    Dapagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued
    Dapagliflozin; Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued
    Deflazacort: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Dexamethasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Dexlansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Didanosine, ddI: (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
    Digoxin: (Minor) Thyroid disease is known to alter the response to digoxin. Digoxin toxicity is more likely to occur in patients with hypothyroidism, while the response to digoxin is diminished in patients with hyperthyroidism. These reactions should be kept in mind when therapy with thyroid hormones is begun or interrupted. When hypothyroid patients are administered thyroid hormone, the dose requirement of digoxin may be increased.
    Dulaglutide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Empagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Empagliflozin; Linagliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
    Empagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Enteral Feedings: (Severe) Certain foods, beverages, and enteral feedings can inhibit the absorption of thyroid hormones. To minimize the risk of an interaction, thyroid hormones should be administered on an empty stomach with a glass of water at least 30 to 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. 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. 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 to 60 minutes.
    Ertugliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Ertugliflozin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Esomeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Esomeprazole; Naproxen: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Estrogens: (Minor) The administration of estrogens can increase circulating concentrations of thyroxine-binding globulin. Increased amounts of thyroxine-binding globulin may result in a reduced clinical response to thyroid hormones. Some hypothyroid patients on estrogen may require larger doses of thyroid hormones.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Exenatide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Fludrocortisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Flunisolide: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluoxymesterone: (Moderate) Coadministration may result in increased thyroid hormone concentrations. Monitor thyroid function during concomitant use in patients taking thyroid hormones. In some patients, the thyroid hormone dosage may need to be reduced. Androgens, such as fluoxymesterone may decrease levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction in patients without thyroid disease. However, a lowered need for thyroid hormone has been noticed in hypothyroid patients in one publication.
    Fluticasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluticasone; Salmeterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluticasone; Vilanterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Food: (Severe) Certain foods, beverages, and enteral feedings can inhibit the absorption of thyroid hormones. To minimize the risk of an interaction, thyroid hormones should be administered on an empty stomach with a glass of water at least 30 to 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. 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. 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 to 60 minutes.
    Formoterol; Mometasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Furosemide: (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
    Glimepiride: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Glimepiride; Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Glimepiride; Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Glipizide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Glipizide; Metformin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Glyburide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Glyburide; Metformin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium 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 calcium supplements.
    Hydantoins: (Minor) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of thyroid hormones, leading to reduced efficacy of the thyroid hormone.
    Hydrocortisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Imatinib: (Moderate) Monitor thyroid stimulating hormone (TSH) concentrations carefully when tyrosine kinase inhibitors like imatinib are used in patients taking thyroid hormones. Cases of clinical hypothyroidism have occurred in patients taking imatinib.
    Indinavir: (Moderate) 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. Patients receiving levothyroxine should be carefully monitored when indinavir is started; if hyperthyroidism is detected, reducing the levothyroxine dose should reestablish a euthyroid state. 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.
    Insulin Degludec; Liraglutide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Insulin Glargine; Lixisenatide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Insulins: (Minor) Monitor patients receiving insulin closely for changes in diabetic control whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced.
    Iodine; Potassium Iodide, KI: (Moderate) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Iodoquinol: (Moderate) Iodoquinol should be used with caution in patients treated with thyroid hormones. Iodine-containing compounds like iodoquinol may result in overt thyroid disease. Increased uptake of iodine by the thyroid may lead to changes in thyroid status, especially in patients with pre-existing thyroid disease. Iodoquinol has been shown to interfere with thyroid function tests for up to 6 months.
    Iohexol: (Moderate) 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 thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Iopamidol: (Moderate) 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 thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Iopromide: (Moderate) 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 thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Ioversol: (Moderate) 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 thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Iron Salts: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Administer oral thyroid hormones at least 4 hours before oral iron sucrose, sucroferric oxyhydroxide. 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.
    Iron: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Isoniazid, INH; Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Isosulfan Blue: (Moderate) 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 thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Ketamine: (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
    Lansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Lansoprazole; Naproxen: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Lanthanum Carbonate: (Moderate) Administer oral thyroid hormones at least 2 hours before or after the administration of lanthanum carbonate. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Thyroid stimulating hormone (TSH) concentrations should be carefully monitored. The bioavailability of levothyroxine was decreased by approximately 40% when administered with lanthanum carbonate.
    L-Asparaginase Escherichia coli: (Moderate) Some hypothyroid patients receiving asparaginase may require reduced doses of thyroid hormone. Other patients may remain euthyroid during combined treatment. MonitorTSH levels and monitor for symptoms of hyperthyroidism; a free-T4 concentration may be useful to assess euthyroidism. Asparaginase may decrease the serum TBG (thyroxine-binding globulin) concentration. Decreased amounts of TBG may result in an increased clinical response to thyroid hormones.
    Linagliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
    Linagliptin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
    Liraglutide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Lithium: (Moderate) 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. Patients receiving thyroid hormones should be monitored for changes in thyroid function when lithium is either initiated or discontinued.
    Lixisenatide: (Minor) When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Magnesium: (Moderate) Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium. Magnesium 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 levothyroxine with products containing oral cations, such as antacids or dietary supplements.
    Maprotiline: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of maprotiline.
    Meglitinides: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Mephobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Repaglinide: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Methimazole: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Methohexital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Methylprednisolone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Miglitol: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Mometasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Non-Ionic Contrast Media: (Moderate) 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 thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Omeprazole; Sodium Bicarbonate: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Orlistat: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of orlistat. Concurrent use may reduce the efficacy of thyroid hormones by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Monitor TSH while orlistat is used concurrently. Hypothyroidism has been reported in patients treated concomitantly with orlistat and levothyroxine postmarketing.
    Pantoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Pentobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Phenobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Polycarbophil: (Moderate) Administer thyroid hormones at least 2 hours before or after the ingestion of calcium polycarbophil. Thyroid hormones are best taken on an empty stomach, and, administration should be separated from medications that might interfere with absorption. Monitor the patient's thyroid function and clinical status if the patient is on calcium polycarbophil treatment. Dietary fiber may bind and decrease the absorption of thyroid hormones from the gastrointestinal tract. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). Calcium salts can chelate oral thyroid hormones within the GI tract when administered simultaneously, also leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from calcium supplements and thyroid hormone interactions. In a study of 8 volunteers, the absorption of levothyroxine decreased from 89% when administered alone to only 86% when administered concomitantly with 1,000 mg of calcium polycarbophil.
    Polysaccharide-Iron Complex: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Potassium Iodide, KI: (Moderate) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Pramlintide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Prednisolone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Prednisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Primidone: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Propylthiouracil, PTU: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Proton pump inhibitors: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Rabeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Raloxifene: (Moderate) Patients prescribed raloxifene while taking thyroid hormones should be advised to take the drugs at separate times (e.g., 12 hours apart) until more data are available. Raloxifene may delay and reduce the oral absorption of levothyroxine (T4). In a case report, a patient with chronic but treated hypothyroidism was taking a stable dose of levothyroxine. The patient required increasing doses of levothyroxine when raloxifene was coadministered; the TSH level remained elevated and serum T4 remained decreased despite an increase in oral levothyroxine dosage. An absorption interaction was suspected and the patient rechallenged on two occasions; a decrease in serum T4 was observed whenever raloxifene and levothyroxine were administered concurrently. The patient's levothyroxine dosage requirements returned to baseline and the TSH value normalized when levothyroxine and raloxifene were administered 12 hours apart rather than simultaneously. The mechanism for the observed interaction is unknown. In theory, raloxifene might cause oral malabsorption of any thyroid hormone containing T4 (e.g., desiccated thyroid, levothyroxine, liotrix) if administered at the same time.
    Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Secobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Semaglutide: (Moderate) Consider increased clinical or laboratory monitoring for thyroid hormones if administered with oral semaglutide as the oral absorption of thyroid hormones may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Levothyroxine exposure was increased by 33% when administered with semaglutide in a drug interaction study. Be sure to administer oral semaglutide as directed, separately from other oral medications. This absorption interaction does not occur with subcutaneous semaglutide or IV levothyroxine. In addition, close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis.
    Sevelamer: (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by several hours. Sevelamer appears to 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 coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
    Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption.
    Simvastatin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Sodium Iodide: (Major) In order to increase thyroid uptake and optimize exposure of thyroid tissue to the radionucleotide, patients must discontinue all medications and supplements that may interfere with iodide uptake into thyroid tissue prior to therapy with sodium iodide I-131, including thyroid hormones. Although various protocols are used, the following withdrawal timing recommendations were set forth in a procedure guideline published by the Society of Nuclear Medicine in February 2002. It is recommended to hold alll T4 thyroid hormones (e.g., levothyroxine) 4 to 6 weeks prior, and to hold all T3 thyroid hormones (e.g., liothyronine) 2 weeks prior, to sodium iodide I-131 therapy.
    Sodium Polystyrene Sulfonate: (Moderate) Administer thyroid hormones at least 4 hours apart from cation exchange resins, like sodium polystyrene sulfonate. Cation exchange resins can bind thyroxine or levothyroxine in the GI tract and inhibit oral absorption, potentially leading to hypothyroidism..
    Somatropin, rh-GH: (Minor) 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.
    Soy Isoflavones: (Moderate) 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. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones. More studies are required to assess the exact mechanism of this interaction.
    Sucralfate: (Moderate) Administer levothyroxine at least 4 hours apart from a dose of sucralfate. Patients treated concomitantly with these drugs should be monitored for changes in thyroid function. Consider an alternative to sucralfate, if appropriate. Concurrent use of sucralfate may reduce the efficacy of levothyroxine and other thyroid hormones by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism.
    Sulfonylureas: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Sympathomimetics: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Teduglutide: (Moderate) Monitor thyroid status and for symptoms of increased thyroid effect. Based upon the pharmacodynamic effect of teduglutide, there is a potential for increased absorption of concomitant oral medications, which should be considered if these drugs require titration or have a narrow therapeutic index, such as orally administered thyroid hormones.
    Theophylline, Aminophylline: (Minor) 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. Aminophylline is converted to theophylline in the body. Aminophylline dosage adjustments may be needed with thyroid hormone replacement. (Minor) 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.
    Thiazolidinediones: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Thiopental: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Tolazamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Tolbutamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Tretinoin, ATRA: (Moderate) 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). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
    Triamcinolone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Tricyclic antidepressants: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of tricyclic antidepressants. Although this drug combination appears to be safe, be aware of the possibility of exaggerated cardiovascular side effects such as arrhythmias and CNS stimulation.
    Warfarin: (Moderate) The concurrent use of thyroid hormones and warfarin potentiates anticoagulation effects of warfarin. The mechanism of this interaction may be the increased catabolism of vitamin K clotting factors as the hypothyroid state is corrected. As a result, the hypoprothrombinemic response to warfarin occurs earlier and to a greater degree. Dextrothyroxine has been shown to potentiate the effects of warfarin. Dextrothyroxine may increase the affinity of warfarin for its receptor sites in addition to increasing the catabolism of vitamin K dependent clotting factors. A reduction in the dosage of warfarin is recommended with concomitant therapy.

    PREGNANCY AND LACTATION

    Pregnancy

    The clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones such as liothyronine are administered during pregnancy. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy. Thyroid hormones undergo minimal placental transfer. Hypothyroidism that is diagnosed during pregnancy should be promptly treated.[46855] [54444] During pregnancy, T4 is thought to be crucial for fetal brain development, and guidelines recommend that levothyroxine be the preferred drug vs. liothyronine for treatment in the pregnant patient. Measure TSH and free-T4 as soon as pregnancy is confirmed and, at a minimum, during each trimester to gauge the adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. For patients with serum TSH above the normal trimester-specific range, increase the dose of thyroid hormone and measure TSH every 4 weeks until a stable dose is reached and serum TSH is within the normal trimester-specific range. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose; monitor thyroid function tests 4 to 8 weeks postpartum to assess for needed adjustments.[46855] [54444]

    In general, thyroid hormones are compatible with breast-feeding. Changes in thyroid status in the post-partum period may require careful monitoring and maternal dosage adjustment. 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. Limited published studies report that liothyronine is present in human milk. There is insufficient information to determine the effects of liothyronine on the breastfed infant and no available information on the effects of liothyronine on milk production. However, thyroid hormones do not have a known tumorigenic potential and are not associated with reports of serious adverse reactions in nursing infants.[46855] [54444] Levothyroxine (T4) is often the preferential drug to treat hypothyroidism in most patients and is considered compatible with breast-feeding.[27500] [60310] The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for the drug and any potential adverse effects on the breastfed infant from liothyronine or the underlying maternal condition.[46855] [54444]

    MECHANISM OF ACTION

    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 4 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 the extrathyroidal conversion of T4 to T3, 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 10 times greater receptor affinity than does T4.[46855] [54444]
     
    The release of T3 and T4 from the thyroid gland into the systemic circulation is regulated by TSH (thyrotropin, also known as thyroid stimulating hormone), 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.[46855] [54444]
     
    Correction of hypothyroidism through the 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 are increased. In primary hypothyroidism, TSH levels should correct when normal levels of thyroid hormone are established.[46855] [54444]

    PHARMACOKINETICS

    Liothyronine may be administered intravenously or orally. Liothyronine is more readily available for use by the body tissues than levothyroxine as it is not as firmly bound to serum proteins, permitting more rapid cell penetration. The higher affinity of levothyroxine (T4) for both thyroid-binding globulin (TBG) and thyroid-binding prealbumin as compared to triiodothyronine (T3) partially explains the higher serum levels and longer half-life of the former hormone. Both protein-bound hormones exist in reverse equilibrium with minute amounts of free hormone. The free hormone portions account for the metabolic activity. The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3, and T3 is further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation. Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. The biological half-life is 2.5 days.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

    Oral Route

    Within 4 hours after oral administration, 95% of an oral dose is absorbed from the gastrointestinal tract. Onset of activity is seen within a few hours. Maximum pharmacological activity occurs within 2 to 3 days, providing early clinical response.

    Intravenous Route

    A single intravenous dose of liothyronine sodium produces a detectable metabolic response within 2 to 4 hours and a maximum therapeutic response within 2 days.