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    Thyroid Preparations

    BOXED WARNING

    Obesity treatment

    Levothyroxine-liothyronine (porcine) thyroid hormone is not indicated for obesity treatment. Normal replacement doses are not effective, and large doses that would be required for reducing weight in euthyroid patients could lead to serious or even life-threatening toxicity. This is particularly dangerous when thyroid hormones are administered along with sympathetic amines that are also often used for weight loss.

    DEA CLASS

    Rx

    DESCRIPTION

    Natural thyroid agent derived from dessicated extract from porcine thyroid glands; tablets provide 38 mcg levothyroxine (T4) and 9 mcg liothyronine (T3) per grain (60 mg) of thyroid
    Used primarily to treat hypothyroidism in adult and pediatric patients
    Due to variations in content, levothyroxine; liothyronine (Porcine) thyroid extracts have been largely replaced by synthetic levothyroxine (T4), the preferred thyroid replacement hormone

    COMMON BRAND NAMES

    Armour Thyroid, Nature Thyroid, Nature-Throid, NP Thyroid, Westhroid, WP Thyroid

    HOW SUPPLIED

    Armour Thyroid/Liothyronine, Levothyroxine/Nature Thyroid/Nature-Throid/NP Thyroid/Westhroid/WP Thyroid Oral Tab: 11.25-47.5mcg, 13.5-57mcg, 15.75-66.5mcg, 18-76mcg, 2.25-9.5mcg, 20.25-85.5mcg, 22.5-95mcg, 27-114mcg, 36-152mcg, 4.5-19mcg, 45-190mcg, 6.75-28.5mcg, 9-38mcg

    DOSAGE & INDICATIONS

    For the treatment of hypothyroidism of any etiology, and for the treatment or prevention of various types of euthyroid (non-toxic) goiter.
    Oral dosage
    Adults

    Initially, 30 mg PO once daily for most patients. A lower dosage of 15 mg PO once daily is recommended for those with long-standing myxedema, especially if cardiovascular impairment is suspected. May increase every 2 to 3 weeks in increments of 15 mg as needed until the appropriate response is obtained. Typical maintenance dose: 60 to 120 mg PO once daily. Dosing guidelines are approximate; individualize based on clinical response and laboratory monitoring. Due to variability in manufacture and product source, desiccated thyroid is not considered a drug of choice; levothyroxine is standard of care for thyroid replacement.

    Adolescents

    Initially, 30 mg PO once daily for most patients. Use lower initial dose for those with long-standing myxedema, especially if cardiovascular impairment is suspected. Typical maintenance doses for adolescents are greater than 90 mg (range: 1.2 mg/kg to 1.8 mg/kg) PO once daily. Titrate every 2 to 3 weeks as needed until the appropriate response is obtained. Dosing guidelines are approximate; individualize based on clinical response and laboratory monitoring. Due to variability in manufacture and product source, desiccated thyroid is not considered a drug of choice; levothyroxine is standard of care for thyroid replacement.

    Children 6 to 12 years

    Initially, initiate at a low dosage, such as 30 mg PO once daily for most patients. Use a lower dosage for those with long-standing myxedema, especially if cardiovascular impairment is suspected. Typical maintenance dose: 60 mg to 90 mg (range: 2.4 mg/kg to 3 mg/kg) PO once daily. Titrate every 2 to 3 weeks as needed. Dosing guidelines are approximate; individualize based on clinical response and laboratory monitoring. Due to variability in manufacture and product source, desiccated thyroid is not considered a drug of choice; levothyroxine is standard of care for thyroid replacement.

    Children 1 to 5 years

    Initially, initiate at a low dosage, such as 30 mg PO once daily for most patients. Use a lower dosage for those with long-standing myxedema, especially if cardiovascular impairment is suspected. Typical maintenance dose: 45 mg to 60 mg (range: 3 mg/kg to 3.6 mg/kg) PO once daily. Titrate every 2 to 3 weeks as needed. Dosing guidelines are approximate; individualize based on clinical response and laboratory monitoring. Due to variability in manufacture and product source, desiccated thyroid is not considered a drug of choice; levothyroxine is standard of care for thyroid replacement.

    Infants 6 months and older

    Initiate at a low dosage and titrate every 2 to 3 weeks as needed until the appropriate response is obtained. In infants with congenital hypothyroidism, therapy with full doses should be instituted as soon as the diagnosis has been made. Typical maintenance doses: 30 mg to 45 mg (range: 3.6 mg/kg to 4.8 mg/kg) PO once daily. Dosing guidelines are approximate; individualize based on clinical response and laboratory monitoring. Due to variability in manufacture and product source, desiccated thyroid is not considered a drug of choice; levothyroxine is standard of care for thyroid replacement.

    Neonates and Infants less than 6 months

    Initiate at a low dosage and titrate every 2 to 3 weeks as needed until the appropriate response is obtained. In infants with congenital hypothyroidism, therapy with full doses should be instituted as soon as the diagnosis has been made. Typical maintenance dose: 15 mg to 30 mg (range: 4.8 mg/kg to 6 mg/kg) PO once daily. Dosing guidelines are approximate; individualize based on clinical response and laboratory monitoring. Due to variability in manufacture and product source, desiccated thyroid is not considered a drug of choice; levothyroxine is standard of care for thyroid replacement.

    MAXIMUM DOSAGE

    Levothyroxine; Liothyronine (Porcine) has a narrow therapeutic index; thyroid dosage must be individualized.

    Adults

    Greater than 120 mg/day PO desiccated thyroid is rarely needed. Failure to respond to doses of 180 mg/day PO suggests lack of compliance or malabsorption.

    Geriatric

    Greater than 120 mg/day PO desiccated thyroid is rarely needed. Failure to respond to doses of 180 mg/day PO suggests lack of compliance or malabsorption.

    Adolescents

    Greater than 120 mg/day PO desiccated thyroid is rarely needed in adolescents in whom growth and puberty are complete. Failure to respond to doses of 180 mg/day PO suggests lack of compliance or malabsorption.

    Children

    Individualize dosage.

    Infants

    Individualize dosage.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Oral Administration

    Administer daily on an empty stomach with a glass of water at least 30 to 60 minutes before breakfast or other food.
    Administer apart from medications and dietary supplements known to decrease levothyroxine-liothyronine (porcine) thyroid hormone absorption.
    Certain formulations (e.g., Armour Thyroid) may have a strong, characteristic odor; this does not indicate that it is spoiled or defective in any way.

    STORAGE

    Armour Thyroid:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Bio-Throid:
    - Store at room temperature (between 59 to 86 degrees F)
    Nature Thyroid:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Nature-Throid:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    NP Thyroid:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    Westhroid :
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)
    WP Thyroid:
    - Protect from light
    - Protect from moisture
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Porcine protein hypersensitivity

    Levothyroxine-liothyronine (porcine) thyroid hormone is a natural product derived from porcine thyroid glands. Although hypersensitivity is not common, desiccated thyroid should not be used in patients with a suspected hypersensitivity to thyroid hormones. In particular, levothyroxine-liothyronine (porcine) thyroid hormone should not be used in patients with a known porcine protein hypersensitivity.

    Thyrotoxicosis

    Levothyroxine-liothyronine (porcine) thyroid hormone is contraindicated in patients with untreated thyrotoxicosis of any etiology. Caution should be used when administering thyroid agents to patients with autonomous thyroid tissue to prevent precipitation of thyrotoxicosis.

    Adrenal insufficiency

    Administration of levothyroxine-liothyronine (porcine) thyroid hormone is contraindicated in patients with uncontrolled adrenal insufficiency because administration can cause adrenal crisis. Adrenal insufficiency should be corrected during concomitant administration of desiccated thyroid since the thyroid hormones increase the body's demand for adrenal hormones. Symptoms of adrenal insufficiency can be unmasked or exacerbated by the administration of thyroid hormones.

    Hypopituitarism

    Other causes of hypothyroidism (e.g., morphologic hypogonadism and nephroses) should be ruled out prior to beginning treatment with levothyroxine-liothyronine (porcine) thyroid hormone. 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, surgery

    Levothyroxine-liothyronine (porcine) thyroid hormone should be used with extreme caution in patients with an acute myocardial infarction (MI) that is not associated with hypothyroidism; small amounts of thyroid hormones may be used only if the MI is complicated or caused by hypothyroidism. Thyroid agents are cardiostimulatory and should be used with great caution in patients with angina pectoris or other preexisting cardiac disease, including uncontrolled hypertension, cardiac arrhythmias, coronary artery disease, or a previous myocardial infarction. Many authorities recommend lower initial dosages and slower titration of thyroid hormones in patients with heart disease. If adverse cardiac symptoms develop or worsen, levothyroxine-liothyronine (porcine) thyroid hormone dosages should be reduced or withheld and cautiously restarted at a lower dose. Excessive 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 thyroid hormones 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.

    Obesity treatment

    Levothyroxine-liothyronine (porcine) thyroid hormone is not indicated for obesity treatment. Normal replacement doses are not effective, and large doses that would be required for reducing weight in euthyroid patients could lead to serious or even life-threatening toxicity. This is particularly dangerous when thyroid hormones are administered along with sympathetic amines that are also often used for weight loss.

    Diabetes mellitus

    Symptoms of diabetes mellitus can be unmasked or exacerbated by the administration of levothyroxine-liothyronine (porcine) thyroid hormone. The use of thyroid hormones 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.

    Osteoporosis

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

    Geriatric

    Caution should be used in geriatric patients since they may be more sensitive to the cardiac effects of levothyroxine-liothyronine (porcine) thyroid hormone replacement. Lower initial dosages and slower titration are recommended. Thyroid hormone requirements are typically 25% lower than in younger adults; individualize dosage. According to the Beers Criteria, levothyroxine-liothyronine (porcine) thyroid hormone is considered a potentially inappropriate medication (PIM) for use in geriatric patients and should be avoided due to concerns about adverse cardiac effects and the availability of the safer alternative and thyroid replacement medication of choice, levothyroxine. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); assessment of thyroid function (e.g., TSH, serum T4 or T3) should occur before initiating thyroid medication and periodically thereafter, including assessment of thyroid function tests when new signs and symptoms of hypothyroidism or hyperthyroidism develop. Initiate thyroid supplementation at low doses and increase gradually to avoid precipitating cardiac failure or adrenal crisis. Because there are many clinically significant medication interactions, re-evaluation of medication doses should occur as clinically indicated.

    Pregnancy

    Levothyroxine-liothyronine (porcine) and other thyroid hormones are considered safe to use during pregnancys. Thyroid hormones undergo minimal placental transfer and human experience does not indicate adverse fetal effects; do not discontinue needed replacement during pregnancy. Hypothyroidism diagnosed during pregnancy should be promptly treated, as untreated hypothyroidism presents a potential for maternal and fetal risk. 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 or other thyroid function tests 6 to 8 weeks postpartum to assess for needed adjustments.

    Breast-feeding

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

    Infertility

    The use of levothyroxine-liothyronine (porcine) thyroid hormone for treatment of female or male infertility is only justified if such infertility is accompanied by hypothyroidism.

    Neonates

    Studies performed to date in children, infants, and neonates have not shown problems that would limit the usefulness of thyroid hormones in these types of patients. Caution is necessary in interpreting results of thyroid function tests in neonates since serum T4 concentrations are transiently elevated and T3 concentrations are transiently low. In addition, the immature pituitary gland is relatively insensitive to the negative feedback effect of thyroid hormones.

    ADVERSE REACTIONS

    Severe

    craniosynostosis / Delayed / Incidence not known
    atrial fibrillation / Early / Incidence not known
    heart failure / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    cardiac arrest / Early / Incidence not known

    Moderate

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

    Mild

    alopecia / Delayed / Incidence not known
    irritability / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    emotional lability / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    weakness / Early / Incidence not known
    nausea / Early / Incidence not known
    headache / Early / Incidence not known
    vomiting / Early / Incidence not known
    fever / Early / Incidence not known
    tremor / Early / Incidence not known
    flushing / Rapid / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    amenorrhea / Delayed / Incidence not known
    insomnia / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    fatigue / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    weight loss / Delayed / Incidence not known
    muscle cramps / 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) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Alogliptin; Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Alpha-glucosidase Inhibitors: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Aluminum Hydroxide: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) To minimize an interaction, administer thyroid hormones at least 4 hours before or after antacids or other drugs containing aluminum hydroxide. Aluminum hydroxide, often found in antacids, interferes with the intestinal absorption of thyroid hormones. Gastric acidity is an essential requirement for adequate absorption of levothyroxine.
    Amiodarone: (Moderate) Amiodarone has a complex effect on the metabolism of thyroid hormones and can alter thyroid function tests in many patients. Since approximately 37% of amiodarone (by weight) is iodine, maintenance doses of 200-600 mg of amiodarone/day result in ingestion of 75-225 mg/day of organic iodide, resulting in much higher total iodine stores in the body. In addition, amiodarone decreases T4 5'-deiodinase activity, which decreases the peripheral conversion of T4 to T3, leading to decreased serum T3. Serum T4 levels are usually normal but may be slightly increased. TSH concentrations usually increase during amiodarone therapy, but after 3 months of continuous administration, TSH concentrations often return to normal. However, amiodarone can cause hypothyroidism or hyperthyroidism, including life-threatening thyrotoxicosis. Therefore, patients receiving levothyroxine and amiodarone should be monitored for changes in thyroid function; because of the slow elimination of amiodarone and its metabolites, abnormal thyroid function tests may persists for weeks or months after amiodarone drug discontinuation.
    Amobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Amoxapine: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of amoxapine. Although this drug combination appears to be safe, clinicians should be aware of the remote possibility of exaggerated cardiovascular side effects such as arrhythmias and CNS stimulation.
    Amoxicillin; Clarithromycin; Lansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Asparaginase Erwinia chrysanthemi: (Moderate) Some hypothyroid patients receiving asparaginase may require reduced doses of thyroid hormone. Other patients may remain euthyroid during combined treatment. MonitorTSH levels and monitor for symptoms of hyperthyroidism; a free-T4 concentration may be useful to assess euthyroidism. Asparaginase may decrease the serum TBG (thyroxine-binding globulin) concentration. Decreased amounts of TBG may result in an increased clinical response to thyroid hormones.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Aspirin, ASA; Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Azelastine; Fluticasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Barbiturates: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Beclomethasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Beta-agonists: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Beta-blockers: (Minor) Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient.
    Betamethasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Budesonide: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Budesonide; Formoterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Butabarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Calcium Acetate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium Carbonate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium Carbonate; Risedronate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium Carbonate; Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium Chloride: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium Gluconate: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Calcium; Vitamin D: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Canagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Canagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Carbamazepine: (Minor) Use carbamazepine and thyroid hormones together with caution. Carbamazepine may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations. Carbamazepine reduces serum protein binding of levothyroxine, and total and free-T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Monitor thyroid hormone parameters.
    Chlorpropamide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Cholestyramine: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of cholestyramine. Cholestyramine and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Chromium: (Moderate) Advise patients to separate chromium supplement ingestion from taking their oral thyroid hormone. For example, taking oral thyroid hormones 1 hours before or 3 hours after chromium picolinate ingestion should minimize an interaction. Chromium could potentially decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested levothyroxine sodium, either taken separately or co-administered with chromium picolinate. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Chromium picolinate significantly decreased the serum thyroxine concentrations. (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Ciclesonide: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Cocaine: (Moderate) The concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further.
    Colesevelam: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colesevelam. Colesevelam and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Colestipol: (Moderate) Administer oral levothyroxine or other oral thyroid hormones at least 4 hours before a dose of colestipol. Colestipol and other bile acid sequestrants have been shown to decrease the oral absorption of thyroid hormones. Monitor thyroid function periodically to ensure proper clinical management.
    Corticosteroids: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Corticotropin, ACTH: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Cortisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    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) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued
    Dapagliflozin; Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued
    Deflazacort: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Dexamethasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Dexlansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Didanosine, ddI: (Moderate) Oral thyroid hormones should be taken at least 2 hours before the administration of certain didanosine formulations to avoid an interaction. Certain didanosine, ddI formulations contain buffers (e.g., chewable/dispersible tablets and oral powder for solution) or are mixed with antacids (e.g., pediatric powder for oral solution). Thyroid hormones are susceptible to drug interactions with buffers/antacids containing aluminum, magnesium, or calcium, which may chelate thyroid hormones within the GI tract and decrease oral thyroid hormone absorption. Gastric acidity is also an essential requirement for adequate absorption of levothyroxine. Hypothyroidism may occur if doses are not separated. The delayed-release didanosine capsules (e.g., Videx EC) do not contain a buffering agent and are not expected to interact with thyroid hormones.
    Digoxin: (Minor) Thyroid disease is known to alter the response to digoxin. Digoxin toxicity is more likely to occur in patients with hypothyroidism, while the response to digoxin is diminished in patients with hyperthyroidism. These reactions should be kept in mind when therapy with thyroid hormones is begun or interrupted. When hypothyroid patients are administered thyroid hormone, the dose requirement of digoxin may be increased.
    Empagliflozin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Empagliflozin; Linagliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
    Empagliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Enteral Feedings: (Severe) Certain foods, beverages, and enteral feedings can inhibit the absorption of thyroid hormones. To minimize the risk of an interaction, thyroid hormones should be administered on an empty stomach with a glass of water at least 30 to 60 minutes prior to food or enteral feedings. Foods that may decrease thyroid hormone absorption include soybean flour and soy-based infant formulas or enteral feedings, as well as high fiber diets, cottonseed meal, and walnuts. In addition to decreasing the oral absorption of thyroid hormones, limited data indicate that soy containing foods and supplements may also influence thyroid physiology. Concentrated soy isoflavones (e.g., genistein and daidzein) may interfere with thyroid peroxidase catalyzed iodination of thyroglobulin, resulting in a decreased production of thyroid hormones and an increased secretion of TSH endogenously. More studies are required to assess the exact mechanism of this interaction. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones. Limited data show that coffee has the potential to impair T4 intestinal absorption. In one report, T4 intestinal absorption was evaluated after the administration of 200 mcg L-thyroxine (L-T4) swallowed with coffee/espresso, water, or water followed 60 minutes later by coffee/espresso. Researchers found that administration with coffee/espresso significantly lowered average serum T4 (p<0.001) and peak serum T4 concentrations (p<0.05) when compared to L-T4 taken with water alone. Coffee/espresso taken 60 minutes after L-T4 ingestion had no significant effect on T4 intestinal absorption. It is prudent to remind patients that thyroid hormones should be separated from food and beverages (other than water), including coffee, by at least 30 to 60 minutes.
    Ertugliflozin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Ertugliflozin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Esomeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Esomeprazole; Naproxen: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Estrogens: (Minor) The administration of estrogens can increase circulating concentrations of thyroxine-binding globulin. Increased amounts of thyroxine-binding globulin may result in a reduced clinical response to thyroid hormones. Some hypothyroid patients on estrogen may require larger doses of thyroid hormones.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Fludrocortisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Flunisolide: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluoxymesterone: (Moderate) Coadministration may result in increased thyroid hormone concentrations. Monitor thyroid function during concomitant use in patients taking thyroid hormones. In some patients, the thyroid hormone dosage may need to be reduced. Androgens, such as fluoxymesterone may decrease levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction in patients without thyroid disease. However, a lowered need for thyroid hormone has been noticed in hypothyroid patients in one publication.
    Fluticasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluticasone; Salmeterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Fluticasone; Vilanterol: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Food: (Severe) Certain foods, beverages, and enteral feedings can inhibit the absorption of thyroid hormones. To minimize the risk of an interaction, thyroid hormones should be administered on an empty stomach with a glass of water at least 30 to 60 minutes prior to food or enteral feedings. Foods that may decrease thyroid hormone absorption include soybean flour and soy-based infant formulas or enteral feedings, as well as high fiber diets, cottonseed meal, and walnuts. In addition to decreasing the oral absorption of thyroid hormones, limited data indicate that soy containing foods and supplements may also influence thyroid physiology. Concentrated soy isoflavones (e.g., genistein and daidzein) may interfere with thyroid peroxidase catalyzed iodination of thyroglobulin, resulting in a decreased production of thyroid hormones and an increased secretion of TSH endogenously. More studies are required to assess the exact mechanism of this interaction. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones. Limited data show that coffee has the potential to impair T4 intestinal absorption. In one report, T4 intestinal absorption was evaluated after the administration of 200 mcg L-thyroxine (L-T4) swallowed with coffee/espresso, water, or water followed 60 minutes later by coffee/espresso. Researchers found that administration with coffee/espresso significantly lowered average serum T4 (p<0.001) and peak serum T4 concentrations (p<0.05) when compared to L-T4 taken with water alone. Coffee/espresso taken 60 minutes after L-T4 ingestion had no significant effect on T4 intestinal absorption. It is prudent to remind patients that thyroid hormones should be separated from food and beverages (other than water), including coffee, by at least 30 to 60 minutes.
    Formoterol; Mometasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Furosemide: (Moderate) Use high doses (more than 80 mg) of furosemide and thyroid hormones together with caution. High doses of furosemide may inhibit the binding of thyroid hormones to carrier proteins, resulting in a transient increase in free thyroid hormones followed by an overall decrease in total thyroid hormone concentrations.
    Glimepiride: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Glimepiride; Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Glimepiride; Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Glipizide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Glipizide; Metformin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Glyburide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Glyburide; Metformin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Hydantoins: (Minor) Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of thyroid hormones, leading to reduced efficacy of the thyroid hormone.
    Hydrocortisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Imatinib: (Moderate) Monitor thyroid stimulating hormone (TSH) concentrations carefully when tyrosine kinase inhibitors like imatinib are used in patients taking thyroid hormones. Cases of clinical hypothyroidism have occurred in patients taking imatinib.
    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: (Moderate) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Iodoquinol: (Moderate) Iodoquinol should be used with caution in patients treated with thyroid hormones. Iodine-containing compounds like iodoquinol may result in overt thyroid disease. Increased uptake of iodine by the thyroid may lead to changes in thyroid status, especially in patients with pre-existing thyroid disease. Iodoquinol has been shown to interfere with thyroid function tests for up to 6 months.
    Iohexol: (Moderate) Radiopaque contrast agents that contain iodine (e.g., iohexol, ioversol, iopamidol, and iodixanol) may cause either hypothyroidism or hyperthyroidism in previously euthyroid patients. Patients receiving thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Iopamidol: (Moderate) Radiopaque contrast agents that contain iodine (e.g., iohexol, ioversol, iopamidol, and iodixanol) may cause either hypothyroidism or hyperthyroidism in previously euthyroid patients. Patients receiving thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Iopromide: (Moderate) Radiopaque contrast agents that contain iodine (e.g., iohexol, ioversol, iopamidol, and iodixanol) may cause either hypothyroidism or hyperthyroidism in previously euthyroid patients. Patients receiving thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Ioversol: (Moderate) Radiopaque contrast agents that contain iodine (e.g., iohexol, ioversol, iopamidol, and iodixanol) may cause either hypothyroidism or hyperthyroidism in previously euthyroid patients. Patients receiving thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Iron Salts: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Administer oral thyroid hormones at least 4 hours before oral iron sucrose, sucroferric oxyhydroxide. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.
    Iron: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Isoniazid, INH; Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Isosulfan Blue: (Moderate) Radiopaque contrast agents that contain iodine (e.g., iohexol, ioversol, iopamidol, and iodixanol) may cause either hypothyroidism or hyperthyroidism in previously euthyroid patients. Patients receiving thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Ketamine: (Moderate) Ketamine should be administered cautiously to patients receiving levothyroxine because concomitant use can cause marked hypertension and tachycardia.
    Lansoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Lansoprazole; Naproxen: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Lanthanum Carbonate: (Moderate) Administer oral thyroid hormones at least 2 hours before or after the administration of lanthanum carbonate. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Thyroid stimulating hormone (TSH) concentrations should be carefully monitored. The bioavailability of levothyroxine was decreased by approximately 40% when administered with lanthanum carbonate.
    L-Asparaginase Escherichia coli: (Moderate) Some hypothyroid patients receiving asparaginase may require reduced doses of thyroid hormone. Other patients may remain euthyroid during combined treatment. MonitorTSH levels and monitor for symptoms of hyperthyroidism; a free-T4 concentration may be useful to assess euthyroidism. Asparaginase may decrease the serum TBG (thyroxine-binding globulin) concentration. Decreased amounts of TBG may result in an increased clinical response to thyroid hormones.
    Levocarnitine: (Moderate) Advise patients to separate chromium supplement ingestion from taking their oral thyroid hormone. For example, taking oral thyroid hormones 1 hours before or 3 hours after chromium picolinate ingestion should minimize an interaction. Chromium could potentially decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested levothyroxine sodium, either taken separately or co-administered with chromium picolinate. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Chromium picolinate significantly decreased the serum thyroxine concentrations.
    Linagliptin: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
    Linagliptin; Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin. (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use oral antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents, such as linagliptin, if thyroid hormones are added or discontinued.
    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: (Moderate) Administer thyroid hormones at least 4 hours before or after antacids, dietary supplements, or other drugs containing magnesium. Magnesium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with products containing oral cations, such as antacids or dietary supplements.
    Maprotiline: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of maprotiline.
    Meglitinides: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Mephobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Metformin: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Repaglinide: (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Metformin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed. (Minor) Thyroid hormone use may result in increased blood sugar and a loss of glycemic control in some patients. Interactions may or may not be clinically significant at usual replacement doses. Monitor blood sugars carefully when thyroid therapy is added, changed, or discontinued in patients receiving metformin.
    Methimazole: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Methohexital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Methylprednisolone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Miglitol: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Mometasone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Non-Ionic Contrast Media: (Moderate) Radiopaque contrast agents that contain iodine (e.g., iohexol, ioversol, iopamidol, and iodixanol) may cause either hypothyroidism or hyperthyroidism in previously euthyroid patients. Patients receiving thyroid hormones and drugs that contain iodine should be monitored for changes in thyroid function.
    Omeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Omeprazole; Sodium Bicarbonate: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Orlistat: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of orlistat. Concurrent use may reduce the efficacy of thyroid hormones by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Monitor TSH while orlistat is used concurrently. Hypothyroidism has been reported in patients treated concomitantly with orlistat and levothyroxine postmarketing.
    Pantoprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Pantothenic Acid, Vitamin B5: (Moderate) Thyroid hormones should be administered at least 4 hours before the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Pentobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Phenobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Pioglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Polycarbophil: (Moderate) Administer thyroid hormones at least 2 hours before or after the ingestion of calcium polycarbophil. Thyroid hormones are best taken on an empty stomach, and, administration should be separated from medications that might interfere with absorption. Monitor the patient's thyroid function and clinical status if the patient is on calcium polycarbophil treatment. Dietary fiber may bind and decrease the absorption of thyroid hormones from the gastrointestinal tract. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). Calcium salts can chelate oral thyroid hormones within the GI tract when administered simultaneously, also leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from calcium supplements and thyroid hormone interactions. In a study of 8 volunteers, the absorption of levothyroxine decreased from 89% when administered alone to only 86% when administered concomitantly with 1,000 mg of calcium polycarbophil.
    Polysaccharide-Iron Complex: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Potassium Iodide, KI: (Moderate) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians coadminister T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Pramlintide: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Prednisolone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Prednisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
    Primidone: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Propylthiouracil, PTU: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
    Proton pump inhibitors: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Rabeprazole: (Moderate) The use of proton pump inhibitors may result in decreased effectiveness of thyroid hormone therapy. Monitor clinically for signs and symptoms of hypothyroidism and altered response to thyroid hormone therapy. Periodically assess the TSH during use of these drugs together. Gastric acidity is an essential requirement for proper and adequate absorption of levothyroxine and other thyroid hormones. Proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce thyroid hormone absorption.
    Raloxifene: (Moderate) Patients prescribed raloxifene while taking thyroid hormones should be advised to take the drugs at separate times (e.g., 12 hours apart) until more data are available. Raloxifene may delay and reduce the oral absorption of levothyroxine (T4). In a case report, a patient with chronic but treated hypothyroidism was taking a stable dose of levothyroxine. The patient required increasing doses of levothyroxine when raloxifene was coadministered; the TSH level remained elevated and serum T4 remained decreased despite an increase in oral levothyroxine dosage. An absorption interaction was suspected and the patient rechallenged on two occasions; a decrease in serum T4 was observed whenever raloxifene and levothyroxine were administered concurrently. The patient's levothyroxine dosage requirements returned to baseline and the TSH value normalized when levothyroxine and raloxifene were administered 12 hours apart rather than simultaneously. The mechanism for the observed interaction is unknown. In theory, raloxifene might cause oral malabsorption of any thyroid hormone containing T4 (e.g., desiccated thyroid, levothyroxine, liotrix) if administered at the same time.
    Rifampin: (Moderate) Rifampin increases thyroid hormone metabolism by inducing uridine 5-diphospho-glucuronosyltransferase (UGT) and leads to lower T4 serum levels. Clinicians should be alert for a decreased response to thyroid hormones if rifampin is used during thyroid hormone therapy.
    Rosiglitazone: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Saxagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Secobarbital: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    Sevelamer: (Moderate) Thyroid hormone oral administration should be separated from sevelamer administration by several hours. Sevelamer appears to decrease the oral absorption of thyroid hormones. In one study of normal volunteers, the subjects (n = 7) ingested orally levothyroxine sodium, either taken separately or coadministered with sevelamer. Serum thyroxine was measured at intervals over a 6-hour period following drug ingestion. Sevelamer significantly decreased the the serum thyroxine concentration. The authors concluded that patients should be advised to separate the time of ingestion of sevelamer from their thyroid hormone preparation.
    Simethicone: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after a dose of simethicone. Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism. Simethicone has been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption.
    Simvastatin; Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Sitagliptin: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements. Oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased oral absorption of the thyroid hormone. For example, ferrous sulfate likely forms a ferric-thyroxine complex.
    Sodium Iodide: (Major) In order to increase thyroid uptake and optimize exposure of thyroid tissue to the radionucleotide, patients must discontinue all medications and supplements that may interfere with iodide uptake into thyroid tissue prior to therapy with sodium iodide I-131, including thyroid hormones. Although various protocols are used, the following withdrawal timing recommendations were set forth in a procedure guideline published by the Society of Nuclear Medicine in February 2002. It is recommended to hold alll T4 thyroid hormones (e.g., levothyroxine) 4 to 6 weeks prior, and to hold all T3 thyroid hormones (e.g., liothyronine) 2 weeks prior, to sodium iodide I-131 therapy.
    Sodium Polystyrene Sulfonate: (Moderate) Administer thyroid hormones at least 4 hours apart from cation exchange resins, like sodium polystyrene sulfonate. Cation exchange resins can bind thyroxine or levothyroxine in the GI tract and inhibit oral absorption, potentially leading to hypothyroidism..
    Somatropin, rh-GH: (Minor) Excessive use of thyroid hormones with growth hormone (somatropin, rh-GH) may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to somatropin. Patients receiving concomitant therapy should be monitored closely to ensure appropriate therapeutic response to somatropin.
    Soy Isoflavones: (Moderate) Concentrated soy isoflavones (e.g., genistein and daidzein) may interfere with thyroid peroxidase catalyzed iodination of thyroglobulin, resulting in a decreased production of thyroid hormones and an increased secretion of TSH endogenously. Caution should be used in administering soy isoflavone supplements concurrently with thyroid hormones. More studies are required to assess the exact mechanism of this interaction.
    Sucralfate: (Moderate) Administer levothyroxine at least 4 hours apart from a dose of sucralfate. Patients treated concomitantly with these drugs should be monitored for changes in thyroid function. Consider an alternative to sucralfate, if appropriate. Concurrent use of sucralfate may reduce the efficacy of levothyroxine and other thyroid hormones by binding and delaying or preventing oral absorption, potentially resulting in hypothyroidism.
    Sulfonylureas: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, discontinued or doses changed.
    Sympathomimetics: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur.
    Teduglutide: (Moderate) Monitor thyroid status and for symptoms of increased thyroid effect. Based upon the pharmacodynamic effect of teduglutide, there is a potential for increased absorption of concomitant oral medications, which should be considered if these drugs require titration or have a narrow therapeutic index, such as orally administered thyroid hormones.
    Theophylline, Aminophylline: (Minor) Correction of hypothyroidism to the euthyroid state may precipitate certain drug interactions. For example, hypothyroidism causes decreased clearance of theophylline, which returns to normal in the euthyroid state. Aminophylline is converted to theophylline in the body. Aminophylline dosage adjustments may be needed with thyroid hormone replacement. (Minor) Correction of hypothyroidism to the euthyroid state may precipitate certain drug interactions. For example, hypothyroidism causes decreased clearance of theophylline, which returns to normal in the euthyroid state. Theophylline dosage adjustments may be needed with thyroid hormone replacement.
    Thiazolidinediones: (Minor) Addition of thyroid hormones to antidiabetic or insulin therapy may result in increased dosage requirements of the antidiabetic agents. Blood sugars should be carefully monitored when thyroid therapy is added, dosages are changed, or if thyroid hormones are discontinued.
    Thiopental: (Minor) Hepatic enzyme-inducing drugs, including barbiturates, can increase the catabolism of thyroid hormones. Be alert for a decreased response to thyroid replacement agents with dosage adjustments, discontinuation or addition of barbiturates during thyroid hormone replacement therapy.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    Levothyroxine-liothyronine (porcine) and other thyroid hormones are considered safe to use during pregnancys. Thyroid hormones undergo minimal placental transfer and human experience does not indicate adverse fetal effects; do not discontinue needed replacement during pregnancy. Hypothyroidism diagnosed during pregnancy should be promptly treated, as untreated hypothyroidism presents a potential for maternal and fetal risk. 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 or other thyroid function tests 6 to 8 weeks postpartum to assess for needed adjustments.

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

    MECHANISM OF ACTION

    Both levothyroxine and liothyronine possess all the actions of endogenous thyroid hormones. 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.
     
    The actions of thyroid hormones are extensive. 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 thyroid-releasing hormone (TRH) secretion from the hypothalamus and by a feedback mechanism dependent on the concentrations of circulating thyroid hormones. 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-liothyronine (porcine) thyroid hormone is administered orally. The distribution of thyroid hormone into the body tissues has not been fully established, but it is believed that desiccated thyroid hormone distributes predominantly into the liver and kidney tissues. It does not appear to cross the placenta, and only minimal amounts are distributed into breast milk. Exogenously administered thyroid hormone is deiodinated in peripheral tissues, with small amounts metabolized in the liver and excreted in the bile. Iodine liberated during metabolism is used for hormone synthesis in the thyroid gland or is excreted in the feces or urine. The half-life of thyroid hormone varies with the concentrations of T3 and T4 in the preparation and typically will fall somewhere between their half-life values, which are approximately 2 days and about 6 to 7 days, respectively.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

    Oral Route

    Levothyroxine-liothyronine (porcine) thyroid hormone is absorbed erratically and incompletely when administered orally, particularly in the presence of food. The average bioavailability of an oral dose is about 50 to 75%. Absorption of T4 can be reduced in patients with malabsorption syndrome, congestive heart failure, or diarrhea. Soybean infant formulas and anionic exchange resins (e.g., cholestyramine) can also decrease absorption of T4. Liothyronine (T3) is almost completely absorbed with 95% being absorbed within 4 hours. The full therapeutic effects of thyroid hormone may not be evident for 1 to 3 weeks following oral administration and persist for the same amount of time following cessation of therapy.