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  • CLASSES

    Thyroid Preparations

    BOXED WARNING

    Obesity treatment

    Thyroid agents should not be used for obesity treatment or for the purpose of weight loss. Normal doses of levothyroxine are not effective in reducing weight in euthyroid patients. Larger doses may produce serious or even life-threatening toxicity, particularly when given in association with sympathetic amines that are used for their anorectic effects.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral synthetic levo-isomer of thyroxine; standardization of hormonal content is advantageous for consistent dosing
    Used for treatment of hypothyroidism of most etiologies, including congenital hypothyroidism (cretinism) and myxedema in adults and pediatric patients
    Used intravenously as a preferred treatment for myxedema coma
    Replacement of thyroid hormone using levothyroxine (T4) is alone sufficient in most individuals with hypothyroidism, and is the preferred replacement therapy for routine use in patients of all ages

    COMMON BRAND NAMES

    Estre, Levo-T, Levothroid, Levoxyl, Synthroid, Thyro-Tabs, Tirosint, Unithroid

    HOW SUPPLIED

    Estre/Levo-T/Levothroid/Levothyroxine Sodium/Levoxyl/Synthroid/Thyro-Tabs/Unithroid Oral Tab: 25mcg, 50mcg, 75mcg, 88mcg, 100mcg, 112mcg, 125mcg, 137mcg, 150mcg, 175mcg, 200mcg, 300mcg
    Levothyroxine Sodium/Synthroid Intravenous Inj Pwd F/Sol: 100mcg, 200mcg, 500mcg
    Tirosint Oral Cap: 13mcg, 25mcg, 50mcg, 75mcg, 88mcg, 100mcg, 112mcg, 125mcg, 137mcg, 150mcg

    DOSAGE & INDICATIONS

    For the treatment of primary hypothyroidism with or without goiter due to diminished or absent thyroid function caused by functional deficiency, primary atrophy, partial or complete absence of the thyroid gland, or from the effects of surgery, radiation, or an antithyroid agent, and for the treatment of secondary (pituitary) or tertiary (hypothalamic) hypothyroidism.
    Oral dosage (capsule and tablet)
    Adults

    If otherwise healthy, initiate at full replacement dosage of roughly 1.6 mcg/kg/day PO. For geriatric patients or if patient has underlying cardiac disease, begin at 12.5 to 25 mcg PO once daily with gradual (12.5 to 25 mcg) increments at 6 to 8 week intervals as needed. Greater than 200 mcg/day is rarely required. Inadequate response to 300 mcg/day or higher may indicate poor compliance, malabsorption, or drug interactions. In patients with severe longstanding hypothyroidism, the recommended initial dose is 12.5 to 25 mcg/day with increases of 12.5 to 25 mcg/day every 2 to 4 weeks.In patients with subclinical hypothyroidism, if treated, a lower levothyroxine sodium dose (e.g., 1 mcg/kg/day) may be adequate. Patients who are not treated should be monitored yearly for changes in clinical status and thyroid laboratory parameters. Per treatment guidelines, levothyroxine is the preferred treatment for hypothyroidism.

    Adolescents in whom growth and puberty are complete

    1.6 mcg/kg/day PO once daily. In patients with severe hypothyroidism, the recommended initial dose is 12.5 to 25 mcg/day with increases of 12.5 to 25 mcg/day every 2 to 4 weeks. Hyperactivity can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose to attain clinical goals.

    Adolescents in whom growth and puberty are incomplete

    2 to 3 mcg/kg/day PO once daily. Hyperactivity can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose until the desired effect is reached. In chronic or severe hypothyroidism, initiate with 25 mcg/day, and increase by 25 mcg every 2 to 4 weeks to attain clinical goals.

    Children 6 to 12 years

    4 to 5 mcg/kg/day PO once daily. Hyperactivity in older children can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose until the recommended dose is reached. In chronic or severe hypothyroidism, initiate with 25 mcg/day, and increase by 25 mcg every 2 to 4 weeks until the desired effect is obtained.

    Children 1 to 5 years

    5 to 6 mcg/kg/day PO once daily. Hyperactivity can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose until the recommended dose is reached. However, in chronic or severe hypothyroidism, initiate with 25 mcg/day, and increase by 25 mcg every 2 to 4 weeks until the desired effect is obtained.

    Infants 6 to 12 months

    6 to 8 mcg/kg/day PO once daily.

    Infants 3 to 5 months

    8 to 10 mcg/kg/day PO once daily.

    Neonates and Infants 1 to 2 months

    10 to 15 mcg/kg/day PO once daily. The dose may be increased every 4 to 6 weeks as needed. Consider lower initial doses (e.g., 25 mcg/day) in neonates/infants with risks for cardiac failure. In neonates/infants with very low (less than 5 mcg/dL) or undetectable serum T4, the initial starting dose is 50 mcg/day PO once daily.

    Oral dosage (solution)
    Adults

    If otherwise healthy, initiate at full replacement dosage of roughly 1.6 mcg/kg/day PO. For geriatric patients or if patient has underlying cardiac disease, begin at 12.5 to 25 mcg PO once daily with gradual (12.5 to 25 mcg) increments at 6 to 8 week intervals as needed. Greater than 200 mcg/day is rarely required. Inadequate response to 300 mcg/day or higher may indicate poor compliance, malabsorption, or drug interactions. In patients with severe longstanding hypothyroidism, the recommended initial dose is 12.5 to 25 mcg/day with increases of 12.5 to 25 mcg/day every 2 to 4 weeks.

    Adolescents in whom growth and puberty are complete

    1.6 mcg/kg/day PO once daily. In patients with severe hypothyroidism, the recommended initial dose is 12.5 to 25 mcg/day with increases of 12.5 to 25 mcg/day every 2 to 4 weeks. Hyperactivity can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose until the desired effect is reached.

    Adolescents in whom growth and puberty are incomplete

    2 to 3 mcg/kg/day PO once daily. Hyperactivity can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose until the desired effect is reached.

    Children 6 to 12 years

    4 to 5 mcg/kg/day PO once daily. Hyperactivity in older children can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose until the recommended dose is reached.

    Children 1 to 5 years

    5 to 6 mcg/kg/day PO once daily. Hyperactivity in older children can be minimized if initiated at a dose that is 25% of the recommended replacement dose. The dose can be increased weekly by an amount equal to 25% of the full recommended replacement dose until the recommended dose is reached.

    Infants 6 to 12 months

    6 to 8 mcg/kg/day PO once daily.

    Infants 3 to 5 months

    8 to 10 mcg/kg/day PO once daily.

    Neonates and Infants younger than 3 months

    10 to 15 mcg/kg/day PO once daily in the morning 30 to 60 minutes before a meal. The dose may be increased every 4 to 6 weeks as needed. Consider lower initial doses in neonates/infants with risks for cardiac failure.

    Intravenous† dosage or Intramuscular† dosage
    Adults

    Initially, 50% of the previously established oral dosage, given IV or IM once daily in patients unable to take oral doses. Some patients may need titration after this initial dosage selection to maintain euthyroid status. If the patient has previously taken their oral medication as directed on an empty stomach, the PO bioavailability of levothyroxine approaches 80% and thus some clinicians use up to 80% of the previously established oral dosage when applying conversions. Based on medical practice, the relative bioavailability between oral and IV administration is estimated to be 48% to 74% and differences in absorption characteristics of patients and how they take their oral medication necessitate the use of TSH measurements a few weeks after initiating therapy to ensure proper dose adjustments. Conversely, if a patient is stabilized on IV or IM dosage, when it is time to convert back to oral dosage, many clinicians use an initial 20% to 25% increase in the IV or IM dosage based on the pharmacokinetic parameters observed in medical practice to convert to an initial oral dosage, with subsequent dosage titration based on clinical and laboratory status to individualize dose and achieve euthyroidism.

    Infants, Children, and Adolescents

    Initially, 50% of the previously established oral dosage, given IV or IM once daily in patients unable to take oral doses. Some patients may need titration after this initial dosage selection to maintain euthyroid status. Based on medical practice, the relative bioavailability between oral and IV administration is estimated to be 48% to 74% and differences in absorption characteristics of patients and how they take their oral medication necessitate the use of TSH measurements a few weeks after initiating therapy to ensure proper dose adjustments.

    Neonates

    Initially, 5 to 8 mcg/kg/day IV in patients initiating levothyroxine who are unable to take oral doses. In patients already taking an oral dose of levothyroxine who require parenteral administration, give 50% to 75% of the oral dose IV once daily. Use TSH measurements to ensure proper dose adjustments.

    For the treatment of myxedema coma.
    Intravenous dosage
    Adults

    300 to 500 mcg IV initially, with an additional 100 to 300 mcg administered on the second day if needed. Continuous daily administration of 75 to 100 mcg IV should be given until the patient is stabilized, and oral administration is feasible. Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism; oral therapy is not recommended since unpredictable absorption from the GI tract may occur. Guidelines state that levothyroxine IV is the preferred therapy: give a loading dose of 200 to 400 mcg IV of levothyroxine, with lower doses given for smaller, older patients and those with a history of coronary disease or arrhythmia. A daily replacement dose of 1.6 mcg/kg body weight, reduced to 75% as long as being administered IV, can be given thereafter. Institute oral therapy after the patient improves clinically.

    For thyroid stimulating hormone (TSH) suppression in thyroid nodules, euthyroid goiters, and well-differentiated thyroid cancer.
    Oral dosage (capsule and tablet)
    Adults

    Suppression of TSH requires higher doses than those used for replacement therapy. Doses are usually greater than 2 mcg/kg/day PO. Individualize dose to the disease treated and desired clinical response. Monitor patient closely with TSH concentrations and clinical status. In general, TSH concentrations are usually suppressed to less than 0.1 mU/L for thyroid cancer; in patients with high-risk tumors, the target concentration for TSH suppression may be less than 0.01 mU/L. For benign thyroid nodules and nontoxic multinodular goiter, the TSH is generally suppressed to a higher target (e.g., 0.1 to either 0.5 or 1 mU/L) than that used for the treatment of thyroid cancer. Levothyroxine is contraindicated if the serum TSH is already suppressed due to the risk of precipitating overt thyrotoxicosis.

    MAXIMUM DOSAGE

    Narrow therapeutic index; dosage must be individualized.

    Adults

    Doses above 200 mcg/day PO rarely needed.

    Elderly

    Doses above 200 mcg/day PO rarely needed.

    Adolescents

    In whom growth and puberty are complete: Doses above 200 mcg/day PO rarely needed.

    Children

    Individualize dosage.

    Infants

    Individualize dosage.

    Neonates

    Individualize dosage.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    Administer on an empty stomach with a full glass of water at least 30 to 60 minutes before breakfast. Administer apart from medications known to decrease absorption and apart from enteral feedings. Bioavailability is best when administered in the fasting state.

    Oral Solid Formulations

    Capsules:
    Do not administer capsules to patients that cannot swallow the intact capsule. The capsules should not be crushed or cut. In addition, the capsules can not be dissolved in water.
     
    Tablets:
    Levothyroxine tablets may rapidly disintegrate; reports exist of choking, gagging, dysphagia, and tablets being stuck in the throat. Instruct patients to take tablets with a full glass of water, which reduces the risk for this problem in most patients.
    Tablets may be crushed and suspended in a small amount (5 to 10 mL) of water, breast milk, or non-soy based infant formula, and administered by spoon or dropper for those unable to swallow whole tablets. Administer immediately after preparation; do not store. Alternatively, an extemporaneous suspension can be prepared.
    Tablets may be crushed and sprinkled over a small amount (5 to 10 mL) of food (e.g., cool apple sauce). Administer immediately after preparation.
    Do not mix crushed tablets with enteral feedings or soybean-based infant formulas; these reduce bioavailability.

    Oral Liquid Formulations

    Levothyroxine oral solution may be administered in water or directly into the mouth.
    To administer in water, squeeze the contents of 1 single unit-dose ampule into a glass or cup containing water and stir. Do NOT dilute with any liquid other than water.
    The preparation should be administered immediately and consumed in its entirety to ensure all of the dose is received. Rinse the glass or cup with additional water and drink the contents to ensure the entire dose is taken.
    To administer directly (without water), either squeeze it into the mouth or onto a spoon and immediately consume.
    Storage: Store unopened ampules in the original container (pouch) at 77 degrees F (25 degrees C); excursions are permitted to 59 to 86 degrees F (15 to 30 degrees C). Discard any unused ampules 15 days after opening the pouch.

    Extemporaneous Compounding-Oral

    Extemporaneous preparation of a 25 mcg/mL levothyroxine oral suspension:
    NOTE: Levothyroxine is not available as an FDA-approved oral suspension.
    With a mortar and pestle, grind twenty-five 0.1 mg levothyroxine tablets into a fine powder.
    In a separate container, measure 40 mL glycerol.
    Add a small amount of the glycerol to the fine powder and mix into a uniform paste. Add geometric amounts of the glycerol until the suspension is pourable.
    Transfer suspension to a calibrated 100 mL amber bottle. In approximately 10 mL portions, rinse the mortar with the remaining glycerol and transfer washings into the amber bottle trying to leave no levothyroxine in the mortar.
    Add water to the amber bottle to bring the total volume to 100 mL.
    Label the bottle appropriately, including 'Shake well before each use' and 'Refrigerate'. The suspension is stable for 8 days when stored at 4 degrees Celsius.

    Injectable Administration

    May be administered by intramuscular injection or intravenously.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
     
    Reconstitution:
    Reconstitute by aseptically adding 5 mL of preservative-free 0.9% Sodium Chloride Injection, USP to a vial of lyophilized levothyroxine sodium for injection. Do not use other solutions to reconstitute. The resultant solution will have a final concentration of approximately 20 mcg/mL and 100 mcg/mL for the 100 mcg and 500 mcg vials, respectively. Shake well to dissolve completely.
    Reconstituted injection is preservative free and is stable for 4 hours; unused portions should be discarded.

    Intravenous Administration

    After reconstitution as directed, do not add levothyroxine sodium for injection to other IV fluids or medications.
    Inject IV via Y-site or a 3-way stopcock at a rate not to exceed 100 mcg per minute.
    In younger patients, inject over 2 to 3 minutes.

    Intramuscular Administration

    Inject deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.

    STORAGE

    Generic:
    - Protect from light
    - Reconstituted product should be used immediately. Discard unused portion
    - Store between 68 to 77 degrees F
    - Store in a dry place
    Estre :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Levo-T:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Levothroid:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Levoxyl:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Synthroid:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Thyro-Tabs:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Tirosint:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Unithroid:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Levothyroxine capsules (Tirosint) are contraindicated for use in anyone unable to swallow a capsule, generally including young children < 6 years of age. Do not cut or crush the capsules.

    Adrenal insufficiency

    Administration of levothyroxine to patients with uncorrected adrenal insufficiency can cause adrenal crisis and thus administration is contraindicated. Thyroid hormone increases metabolic clearance of glucocorticoids. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with levothyroxine.

    Hypopituitarism

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

    Acute myocardial infarction, angina, cardiac arrhythmias, cardiac disease, coronary artery disease, hypertension, myocardial infarction

    All levothyroxine dosage formulations are cardiostimulatory and should be used with great caution in patients with angina pectoris or other preexisting cardiac disease, including uncontrolled hypertension, cardiac arrhythmias, coronary artery disease, or an acute myocardial infarction or a previous myocardial infarction; do not use levothyroxine therapy in patients with heart disease and nontoxic diffuse goiter or nodular thyroid disease if the serum TSH concentration is suppressed. Many authorities recommend lower initial dosages and slower titration of thyroid hormones in patients with heart disease. If adverse cardiac symptoms develop or worsen, reduce or withhold levothyroxine and cautiously restart at a lower dose. Over-treatment with thyroid hormones may cause cardiac stimulation and lead to increased heart rate, cardiac wall thickening and increased cardiac contractility, which may precipitate angina or cardiac arrhythmias. Concomitant administration of levothyroxine with sympathomimetic agents in patients with coronary artery disease may precipitate coronary insufficiency and associated symptoms. Patients with coronary artery disease who are receiving thyroid hormones may be at a higher risk for developing arrhythmias, particularly during surgery. Monitor patients receiving concomitant levothyroxine and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiac symptoms develop or worsen, reduce the SYNTHROID dose or withhold for 1 week and restart at a lower dose.

    Diabetes mellitus

    Symptoms of diabetes mellitus can be unmasked or exacerbated by the administration of thyroid agents. The use of levothyroxine may require alteration in the dosage of antidiabetic regimens. Blood glucose should be monitored closely during concomitant therapy. In addition, withdrawal of thyroid hormones may cause hypoglycemia in susceptible patients.

    Obesity treatment

    Thyroid agents should not be used for obesity treatment or for the purpose of weight loss. Normal doses of levothyroxine are not effective in reducing weight in euthyroid patients. Larger doses may produce serious or even life-threatening toxicity, particularly when given in association with sympathetic amines that are used for their anorectic effects.

    Infertility

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

    Osteoporosis

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

    Pregnancy

    Thyroid hormones undergo minimal placental transfer and human experience does not indicate increased rates of major birth defects or miscarriages; do not discontinue needed replacement during pregnancy. Also, hypothyroidism diagnosed during pregnancy should be promptly treated. Measure TSH during each trimester to gauge adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose, monitor a serum TSH 6 to 8 weeks postpartum to assess for needed adjustments.

    Breast-feeding

    Thyroid hormones, like levothyroxine, are generally compatible with breast-feeding; minimal amounts of thyroid hormones are excreted in breast milk. Levothyroxine is compatible with breast-feeding due to a lack of reported adverse effects in nursing infants. It should be noted that in general, adequate thyroid replacement doses are needed to maintain normal lactation; levothyroxine is often the drug of choice to treat hypothyroidism during pregnancy and lactation. Comparisons of the levels of TSH and other thyroid function tests between breast-fed and bottle-fed infants have been published. Breast milk does not provide sufficient levothyroxine (T4) or liothyronine (T3) to prevent the effects of congenital hypothyroidism; therefore serum levels of TSH in breast-fed hypothyroid infants are markedly elevated. Euthyroid babies who were breast-fed did not have differences in TSH levels when compared to euthyroid babies receiving formula feedings. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Dysphagia

    Use caution when administering the Levoxyl brand of levothyroxine tablets to patients with dysphasia or other conditions that compromise the ability to swallow. Choking, gagging, tablets getting stuck in the throat, and dysphagia have been reported, mainly when the intact tablets were not taken with water. Counsel patients to take the tablet with water.

    Geriatric

    Caution should be used in geriatric patients since they may be more sensitive to the cardiac effects of thyroid replacement. In general, lower initial dosages and slower titration are recommended in elderly patients. Overall, thyroid hormone requirements in the elderly are typically 25% lower than in younger adults. Individualization of dosing is recommended. Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with levothyroxine overtreatment in the elderly. According to the Beers Criteria, levothyroxine is the safer alternative versus other thyroid replacement medications and guidelines state levothyroxine is the agent of choice for most patients for hypothyroidism. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, assessment of thyroid function (e.g., TSH, serum T4 or T3) should occur before initiating treatment with a thyroid medication and periodically thereafter, including assessment of thyroid function tests when new signs and symptoms of hypothyroidism or hyperthyroidism develop. Initiation of thyroid supplementation should occur at low doses and be increased 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.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    heart failure / Delayed / Incidence not known

    Moderate

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

    Mild

    emotional lability / Early / Incidence not known
    vomiting / Early / Incidence not known
    flushing / Rapid / Incidence not known
    fatigue / Early / Incidence not known
    weakness / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    nausea / Early / Incidence not known
    insomnia / Early / Incidence not known
    tremor / Early / Incidence not known
    headache / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    fever / Early / Incidence not known
    amenorrhea / Delayed / Incidence not known
    anorexia / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    irritability / Delayed / Incidence not known
    alopecia / Delayed / 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.
    Alendronate: (Moderate) Separating times of administration of alendronate from levothyroxine and other medications will maximize alendronate absorption and clinical benefit. For example, administering the levothyroxine dose at bedtime can avoid this interaction with alendronate. The bioavailability of alendronate was slightly decreased when alendronate and levothyroxine were co-administered to healthy subjects The mean AUC and Cmax of alendronate decreased by 7% and 9%, respectively. Alendronate should always be administered upon arising for the day and at least 30 minutes before the first food, beverage, or other medication of the day. To minimize interactions, levothyroxine is also best taken on an empty stomach with a glass of water.
    Alendronate; Cholecalciferol: (Moderate) Separating times of administration of alendronate from levothyroxine and other medications will maximize alendronate absorption and clinical benefit. For example, administering the levothyroxine dose at bedtime can avoid this interaction with alendronate. The bioavailability of alendronate was slightly decreased when alendronate and levothyroxine were co-administered to healthy subjects The mean AUC and Cmax of alendronate decreased by 7% and 9%, respectively. Alendronate should always be administered upon arising for the day and at least 30 minutes before the first food, beverage, or other medication of the day. To minimize interactions, levothyroxine is also best taken on an empty stomach with a glass of water.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully 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.
    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: (Major) Aluminum hydroxide interferes with the intestinal absorption of thyroid hormones. To minimize this interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum.
    Aluminum Hydroxide; Magnesium Carbonate: (Major) Aluminum hydroxide interferes with the intestinal absorption of thyroid hormones. To minimize this interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum.
    Aluminum Hydroxide; Magnesium Hydroxide: (Major) Aluminum hydroxide interferes with the intestinal absorption of thyroid hormones. To minimize this interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Aluminum hydroxide interferes with the intestinal absorption of thyroid hormones. To minimize this interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum. (Major) Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of simethicone.
    Aluminum Hydroxide; Magnesium Trisilicate: (Major) Aluminum hydroxide interferes with the intestinal absorption of thyroid hormones. To minimize this interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum.
    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 Carbonate: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    Calcium Carbonate; Magnesium Hydroxide: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    Calcium Carbonate; Risedronate: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    Calcium Salts: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    Calcium: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    Calcium; Vitamin D: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of 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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully 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.
    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: (Major) Cholestyramine has been shown to decrease the absorption of thyroid hormones. To minimize this interaction, administer thyroid hormones at least 4 hours before or after cholestyramine.
    Chromium: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements. (Major) Chromium could potentially decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or co-administered with chromium picolinate. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Chromium picolinate significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve. The authors concluded that patients should be advised to separate the time of ingestion of chromium from their thyroid hormone preparation. Administering levothyroxine 1 hours before or 3 hours after chromium picolinate ingestion, for example, should minimize the potential for an interaction.
    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.
    Colesevelam: (Moderate) The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy. To minimize potential for interactions, consider administering oral drugs with a narrow therapeutic index, such as liothyronine, at least 4 hours before colesevelam. There have been rare reports of elevated thyroid stimulating hormone (TSH) concentrations in patients who have received colesevelam coadministered with thyroid hormone replacement therapy.
    Colestipol: (Major) Colestipol has been shown to decrease the absorption of thyroid hormones. To minimize this interaction, administer thyroid hormones at least 4 hours before or after colestipol.
    Collagenase: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    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.
    Cyanocobalamin, Vitamin B12: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    Cyclosporine: (Moderate) Serum trough cyclosporine concentrations appear to be reduced by concurrent oral cyclosporine and levothyroxine use. Claosely monitor cyclosporine concentrations with concomitant levothyroxine therapy. Among 10 patients who took cyclosporine (Neoral) capsules twice daily for at least a year and oral levothyroxine 100 mcg daily for at least 3 months, the trough serum cyclosporine concentration was significantly lower as compared with values from 30 patients who only took cyclosporine. The mechanism of the interaction may be decreased oral cyclosporine absorption. Cyclosporine is a substrate of P-glycoprotein (P-gp), and levothyroxine appears to be an inducer of intestinal P-gp.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully 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
    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: (Major) Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric oral powder for solution). Thyroid hormones should be administered at least 2 hours before the administration of these ddI formulations to avoid an interaction. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and would not be expected to interact with thyroid hormones.
    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.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully 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.
    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.
    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: (Major) Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Major) Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.
    Ferric Citrate: (Moderate) Although drug interaction studies have not been conducted, it may be prudent to separate the timing of administration of thyroid hormones from ferric citrate. According to the manufacturer of ferric citrate, clinicians should consider separating the timing of administration of ferric citrate and drugs where a reduction in the bioavailability of would have a clinically significant effect on its safety or efficacy. Because thyroid hormones have a narrow therapeutic index, consider monitoring clinical response and serum concentrations during concurrent use of ferric citrate.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    Hetastarch; Dextrose; Electrolytes: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of 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.
    Incretin Mimetics: (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 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.
    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.
    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: (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.
    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: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements. (Major) Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Major) According to the manufacturer, oral iron sucrose should not be prescribed with oral levothyroxine. 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: (Major) Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Drugs that possess hepatic enzyme-inducing properties, such as rifampin, can increase the catabolism of levothyroxine and other thyroid hormones. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Isoniazid, INH; Rifampin: (Moderate) Drugs that possess hepatic enzyme-inducing properties, such as rifampin, can increase the catabolism of levothyroxine and other thyroid hormones. 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: (Major) Administer thyroid hormones at least 2 hours before or after the administration of lanthanum carbonate. The bioavailability of levothyroxine was decreased by approximately 40% when administered with lanthanum carbonate. Thyroid stimulating hormone (TSH) concentrations should be carefully monitored during coadministration 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.
    Levocarnitine: (Major) Chromium could potentially decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or co-administered with chromium picolinate. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Chromium picolinate significantly (p < 0.05) decreased the area under the serum thyroxine concentration curve. The authors concluded that patients should be advised to separate the time of ingestion of chromium from their thyroid hormone preparation. Administering levothyroxine 1 hours before or 3 hours after chromium picolinate ingestion, for example, should minimize the potential for an interaction.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully 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, such as linagliptin, if thyroid hormones are added or discontinued.
    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.
    Magnesium: (Major) 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. Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    Metformin; Repaglinide: (Minor) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    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) Addition of thyroid hormones to metformin may result in increased dosage requirements of metformin. Monitor blood sugars carefully when thyroid therapy is added, discontinued or doses changed.
    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: (Major) Antacids have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Administer thyroid hormones at least 4 hours before or after antacids. (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: (Major) Patients treated with orlistat and thyroid hormones should be monitored for changes in thyroid function; orlistat may interfere with the absorption of thyroid hormones from the gastrointestinal tract. A recommendation regarding the separation of thyroid hormones and orlistat administration by at least 4 hours has not been made, but may be prudent.
    Oxcarbazepine: (Minor) Drugs that possess hepatic enzyme-inducing properties, such as oxcarbazepine, may increase the catabolism of levothyroxine and other thyroid hormones. While levothyroxine levels may fall 20 to 40%, many patients are able to remain euthyroid despite co-therapy. Clinicians should simply be alert for a decreased response to thyroid hormones if oxcarbazepine is used during thyroid hormone therapy, and adjust to individual patient response.
    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.
    Pantothenic Acid, Vitamin B5: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    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: (Major) 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. Polycarbophil is a dietary fiber, and dietary fiber may bind and decrease the absorption of thyroid hormones from the gastrointestinal tract. Calcium salts can 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 calcium supplements and thyroid hormone interactions. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). In a study of 8 volunteers, the absorption of levothyroxine decreased from 89% when administered alone to only 86% when administered concomitantly with 1000 mg of calcium polycarbophil.
    Polysaccharide-Iron Complex: (Major) Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.
    Potassium Iodide, KI: (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.
    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.
    Pyridoxine, Vitamin B6: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.
    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: (Major) 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 malabsorption of any thyroid hormone containing T4 (e.g., desiccated thyroid, levothyroxine, liotrix) if administered at the same time. Patients prescribed raloxifene while taking these thyroid hormones should be advised to take the drugs at separate times (e.g., 12 hours apart) until more data are available.
    Rifabutin: (Moderate) Drugs that possess hepatic enzyme-inducing properties, such as rifabutin, can increase the catabolism of levothyroxine and other thyroid hormones. Clinicians should be alert for a decreased response to thyroid hormones if rifabutin is used during thyroid hormone therapy.
    Rifampin: (Moderate) Drugs that possess hepatic enzyme-inducing properties, such as rifampin, can increase the catabolism of levothyroxine and other thyroid hormones. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Rifapentine: (Moderate) Rifapentine induces hepatic isoenzymes CYP3A4 and CYP2C8/9. Drugs metabolized by CYP3A4 and CYP2C8/9, such as thyroid hormones, may require dosage adjustments when administered concurrently with rifapentine.
    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.
    Sevelamer: (Moderate) Sevelamer could potentially decrease the oral absorption of other medications; the alteration can be clinically significant for drugs with a narrow therapeutic window such as the thyroid hormones. 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 (p <0.05) decreased the area under the serum thyroxine concentration curve. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
    Simethicone: (Major) Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of simethicone.
    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 Bicarbonate: (Major) Antacids have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Administer thyroid hormones at least 4 hours before or after antacids.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Major) Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.
    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: (Major) Cation exchange resins like sodium polystyrene sulfonate, can bind thyroxine or levothyroxine in the GI tract and inhibit T4 absorption. Administer thyroid hormones at least 4 hours apart from cation exchange resins.
    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: (Major) Concurrent use of sucralfate may reduce the efficacy of levothyroxine and other thyroid hormones by binding and delaying or preventing absorption, potentially resulting in hypothyroidism. 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.
    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 aminophylline, which returns to normal in the euthyroid state. 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.
    Tirofiban: (Minor) Data from the PRISM study, indicate that patients who received levothyroxine or omeprazole concomitantly with tirofiban had a higher rate of tirofiban clearance than patients who did not receive levothyroxine or omeprazole. The clinical significance of this is unknown.
    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.
    Zinc Salts: (Major) 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. To avoid the interaction, thyroid hormones should be administered at least 4 hours before or after ingestion of oral calcium supplements.

    PREGNANCY AND LACTATION

    Pregnancy

    Thyroid hormones undergo minimal placental transfer and human experience does not indicate increased rates of major birth defects or miscarriages; do not discontinue needed replacement during pregnancy. Also, hypothyroidism diagnosed during pregnancy should be promptly treated. Measure TSH during each trimester to gauge adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose, monitor a serum TSH 6 to 8 weeks postpartum to assess for needed adjustments.

    Thyroid hormones, like levothyroxine, are generally compatible with breast-feeding; minimal amounts of thyroid hormones are excreted in breast milk. Levothyroxine is compatible with breast-feeding due to a lack of reported adverse effects in nursing infants. It should be noted that in general, adequate thyroid replacement doses are needed to maintain normal lactation; levothyroxine is often the drug of choice to treat hypothyroidism during pregnancy and lactation. Comparisons of the levels of TSH and other thyroid function tests between breast-fed and bottle-fed infants have been published. Breast milk does not provide sufficient levothyroxine (T4) or liothyronine (T3) to prevent the effects of congenital hypothyroidism; therefore serum levels of TSH in breast-fed hypothyroid infants are markedly elevated. Euthyroid babies who were breast-fed did not have differences in TSH levels when compared to euthyroid babies receiving formula feedings. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Levothyroxine exhibits all the actions of endogenous thyroid hormone. Liothyronine (T3) is the principal hormone that exhibits these actions whereas levothyroxine (T4) is the major hormone secreted by the thyroid gland and is metabolically deiodinated to T3 in peripheral tissues. Serum concentrations of T4 and TSH are typically used as the primary monitoring parameters for determining thyroid function.In general, thyroid hormones influence the growth and maturation of tissues, increase energy expenditure, and affect the turnover of essentially all substrates. These effects are mediated through control of DNA transcription and, ultimately, protein synthesis. Thyroid hormones play an integral role in both anabolic and catabolic processes and are particularly important to the development of the central nervous system in newborns. They regulate cell differentiation and proliferation, and aid in the myelination of nerves and the development of axonal and dendritic processes in the nervous system. Thyroid hormones, along with somatotropin, are responsible for regulating growth, particularly of bones and teeth. Thyroid hormones also decrease cholesterol concentrations in the liver and the bloodstream, and have a direct cardiostimulatory action. Cardiac consumption is increased by the administration of thyroid hormone, resulting in an increased cardiac output. Administration of exogenous thyroid hormone to patients with hypothyroidism increases the metabolic rate by enhancing protein and carbohydrate metabolism, increasing gluconeogenesis, facilitating the mobilization of glycogen stores, and increasing protein synthesis. In response to reestablishing physiologic levels of thyroid hormone, thyroid-stimulating hormone (TSH) concentrations correct if the primary disorder is at the level of the thyroid.The release of T3 and T4 from the thyroid gland into the systemic circulation is regulated by TSH (thyrotropin), which is secreted by the anterior pituitary gland. Thyrotropin release is controlled by the secretion of thyroid-releasing hormone (TRH) from the hypothalamus and by a feedback mechanism dependent on the concentrations of circulating thyroid hormones. When circulating T3 and T4 levels increase, TRH and TSH decrease. Because of this feedback mechanism, the administration of pharmacologic doses of exogenous thyroid hormone to patients with a normal thyroid suppresses endogenous thyroid hormone secretion.

    PHARMACOKINETICS

    Levothyroxine is administered orally or intravenously. Over 99% of levothyroxine (T4) is bound to proteins, primarily thyroxine-binding globulin (TGB), prealbumin, and albumin. These proteins have a higher affinity for T4 than for liothyronine (T3). Many medications and concurrent clinical conditions may affect T4 protein-binding, resulting in clinically significant changes in thyroid hormone activity since free (unbound) drug is metabolically active. Thyroid hormones do not readily cross the placental barrier, and only minimal amounts are distributed into breast milk.
     
    Levothyroxine (T4) exhibits a slow metabolic clearance. 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, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and rT3 are 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. Approximately 20% of T4 is eliminated in the feces. Urinary excretion of T4 decreases with age. The elimination half-life of levothyroxine is 6 to 7 days in euthyroid patients, 9 to 10 days in hypothyroid patients, and 3 to 4 days in hyperthyroid patients. The elimination half-life of T3 is 2 days or less. Levothyroxine has a slower onset of action and a longer duration than liothyronine. Full therapeutic effects of levothyroxine may not be evident for 1 to 3 weeks following oral administration and persist for the same amount of time following cessation of therapy. As the hypothyroid patient becomes euthyroid, TSH secretion decreases.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: uridine 5'-diphospho-glucuronosyltransferase (UGT), and possibly intestinal P-glycoprotein (P-gp)
    The induction of uridine 5'-diphospho-glucuronosyltransferase (UGT) by other medications increases L-thyroxine hepatic metabolism and leads to a lower T4 serum levels. The literature has reported that levothyroxine might inhibit P-gp, and lower cyclosporine concentrations; however, this action of levothyroxine requires further study.

    Oral Route

    Absorption of orally administered levothyroxine (T4)  from the gastrointestinal tract ranges from 40% to 80%. Based on medical practice, the relative bioavailability of oral levothyroxine is 48 to 74% that of the injectable levothyroxine sodium. The majority of the levothyroxine dose is absorbed from the jejunum and upper ileum. The relative bioavailability of the oral tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 93%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption. Certain foods, like soybean infant formula, enteral feedings, and dietary fiber, decrease T4 absorption.
     
    Consistent tablet potency was an issue with oral levothyroxine products prior to 1984. In 1984, the USP required all manufacturers to use HPLC to monitor levothyroxine tablet content to ensure tablet potency. With the new manufacturing and testing processes, oral levothyroxine product potency issues have not been a significant problem.

    Intravenous Route

    Following intravenous (IV) administration, the synthetic levothyroxine is 100% available and cannot be distinguished from the natural hormone that is secreted endogenously. Levothyroxine injection produces a gradual increase in the circulating concentrations of the hormone with an approximate half-life of 9 to 10 days in hypothyroid patients. Intravenous levothyroxine treatment in severely hypothyroid patients may lead to improvement in cardiovascular, renal, pulmonary, and metabolic parameters within a week. Serum thyroxine and triiodothyronine concentrations may improve or normalize with a similar time frame, with more gradual improvement in serum TSH.