"Oct. 28, 2011 - Nine out of 10 "thyroid support" pills tested by Mayo Clinic researchers contain "risky" levels of thyroid hormones.
A wide range of supplements that claim to support or improve thyroid function are available online an"...
Musculoskeletal: tremors, muscle weakness;
Pseudotumor cerebri has been reported in children receiving levothyroxine therapy. Seizures have been reported rarely with the institution of levothyroxine therapy. Inadequate levothyroxine dosage will produce or fail to ameliorate the signs and symptoms of hypothyroidism.
Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various Gl symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.
Read the Unithroid (levothyroxine sodium) Side Effects Center for a complete guide to possible side effects
Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to UNITHROID (levothyroxine sodium) . In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and action of other drugs. A listing of drug-thyroidal axis interactions is contained in Table 2.
The list of drug-thyroidal axis interactions in Table 2 may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.
|Table 2: Drug-Thyroidal Axis Interactions|
Drug or Drug Class
Drugs that may reduce TSH secretion - the reduction is not
sustained; therefore, hypothyroidism does not occur
Dopamine/Dopamine Agonists Glucocorticoids Octreotide
Use of these agents may result in a transient reduction in TSH secretion when administered at the following doses: dopamine ( ≥ 1µg/kg/min); Glucocorticoids (hydrocortisone ≥ 100 mg/day or equivalent); Octreotide ( > 100 ug/day).
Drugs that alter thyroid hormone secretion
|Drugs that may decrease thyroid hormone secretion, which may result in hypothyroidism|
Long-term lithium therapy can result in goiter in up to 50% of patients, and either subclinical or overt hypothyroidism, each in up to 20% of patients. The fetus, neonate, elderly and euthyroid patients with underlying thyroid disease (e.g., Hashimotos thyroiditis or with Graves disease previously treated with radioiodine or surgery) are among those individuals who are particularly susceptible to iodine- induced hypothyroidism. Oral cholecystographic agents and amiodarone are slowly excreted, producing more prolonged hypothyroidism than parenterally administered iodinated contrast agents. Long-term aminoglutethimide therapy may minimally decrease T4 and T3 levels and increase TSH, although all values remain within normal limits in most patients.
Drugs that may increase thyroid hormone secretion, which may result in hyperthyroidism
Amiodarone Iodide (including iodine-containing radiographic contrast agents)
Iodide and drugs that contain pharmacologic amounts of iodide may cause hypothyroidism in euthyroid patients with Graves disease previously treated with antithyroid drugs or in euthyroid patients with thyroid autonomy (e.g., multinodular goiter or hyperfunctioning thyroid adenoma). Hyperthyroidism may develop over several weeks and may persist for several months after therapy discontinuation. Amiodarone may induce hyperthyroidism by causing thyroiditis.
Drugs that may decrease T4 absorption, which may result in hypothyroidism
|Antacids —Aluminum & Magnesium Hydroxides —Simethicone Bile Acid Sequestrants —Cholestyramine —Colestipol Calcium Carbonate Cation Exchange Resins —Kayexalate Ferrous Sulfate Sucralfate|| |
Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing absorption, potentially resulting in hypothyroidism. Calcium carbonate may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex. Administer levothyroxine at least 4 hours apart from these agents.
Drugs that may alter T4 and T3 serum transport (changes in total T4) - but FT4 concentrations remain normal; and, therefore, hyperthyroidism does not occur
|Drugs that may increase serum TBG concentration|| |
Drugs that may decrease
serum TBG concentration
|Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin / Methadone 5-Fluorouracil Mitotane Tamoxifen|| |
Androgens / Anabolic Steroids
Slow-Release Nicotinic Acid
Drugs that may cause protein-binding site displacement
|Furosemide ( > 80 mg IV) Heparin Hydantoins Non Steroidal Anti-lnflammatory Drugs —Fenamates —Phenylbutazone Salicylates ( > 2 g/day)|| |
Administration of these agents with levothyroxine results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations and, therefore, patients are clinically euthyroid. Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4, is followed by return of FT4 to normal levels with sustained therapeutic serum salicylate concentrations, although total-T4 levels may decrease by as much as 30%.
Drugs that may alter T4 and T3 metabolism
Drugs that may increase hepatic metabolism, which may result in hypothyroidism
Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased Ievothyroxine requirements. Phenytoin and carbamazepine reduce 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.
Drugs that may decrease T4 5 - deiodinase activity
Amiodarone Beta-adrenergic antagonists —(e.g., Propranolol > 160 mg/day) Glucocorticoids —(e.g., Dexamethasone ≥ 4 mg/day) Propylthiouracil (PTU)
Administration of these enzyme inhibitors decrease the peripheral conversion of T4 to T3, Ieading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased. In patients treated with large doses of propranolol ( > 160 mg/day), T3 and T4 levels change slightly, TSH levels remain normal, and patients are clinically euthyroid. It should be noted that actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state. Short-term administration of large doses of gluco- corticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels. However, long- term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (see above).
Thyroid hormones appear to increase the catabolism of vitamin K-dependent clotting factors, thereby increasing the anticoagulant activity of oral anticoagulants. Concomitant use of these agents impairs the compensatory increases in clotting factor synthesis. Prothrombin time should be carefully monitored in patients taking levothyroxine and oral anticoagulants and the dose of anticoagulant therapy adjusted accordingly.
Concurrent use of tri/tetracyclic antidepressants and levothyroxine may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk of cardiac arrhythmias and CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.
Antidiabetic Agents —Biguanides —Meglitinides Sulfonylureas Thiazolidediones Insulin
Addition of levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued.
Serum digitalis glycoside levels may be reduced in hyper-thyroidism or when the hypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalis glycosides may be reduced.
Therapy with interferona has been associated with the development of antithyroid microsomal antibodies in 20% of patients and some have transient hypothyroidism, hyperthyroidism, or both. Patients who have antithyroid antibodies before treatment are at higher risk for thyroid dysfunction during treatment. Interleukin-2 has been associated with transient painless thyroiditis in 20% of patients. Interferon- b and g have not been reported to cause thyroid dysfunction.
Excessive use of thyroid hormones with growth hormones may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to growth hormone.
Methylxanthine Bronchodilators —(e.g., Theophylline)
Decreased theophylline clearance may occur in hypo-thyroid patients; clearance returns to normal when the euthyroid state is achieved.
Thyroid hormones may reduce the uptake of 123I, 131I, and 99mTc.
Concurrent use may increase the effects of sympatho-Mimetics or thyroid hormone. Thyroid hormones May increase the risk of coronary insufficiency when Sympathomimetic agents are administered to patients With coronary artery disease.
Chloral Hydrate Diazepam Ethionamide Lovastatin Metoclopramide 6-ercaptopurine Nitroprusside Para-aminosalicylate sodium Perphenazine Resorcinol(excessivetopical use) Thiazide Diuretics
These agents have been associated with thyroid hormone and/or TSH level alterations by various mechanisms.
Oral anticoagulantsLevothyroxine increases the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the UNITHROID (levothyroxine sodium) dose is increased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments (see Table 2). Digitalis glycosides—The therapeutic effects of digitalis glycosides may be reduced by levothyroxine. Serum digitalis glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides (see Table 2).
Drug-Food Interactions—Consumption of certain foods may affect levothyroxine absorption thereby necessitating adjustments in dosing. Soybean flour (infant formula), cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine sodium from the Gl tract.
Drug-Laboratory Test Interactions—Changes in TBG concentration must be considered when interpreting T4 and T3 values, which necessitates measurement and evaluation of unbound (free) hormone and/or determination of the free T4 index (FT4I). Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen or corticosteroid therapy (see also Table 2). Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.
Carcinogenesis, Mutagenesis, and Impairment of Fertility—Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of levothyroxine. The synthetic T4 in UNITHROID (levothyroxine sodium) is identical to that produced naturally by the human thyroid gland. Although there has been a reported association between prolonged thyroid hormone therapy and breast cancer, this has not been confirmed. Patients receiving UNITHROID (levothyroxine sodium) for appropriate clinical indications should be titrated to the lowest effective replacement dose.
PregnancyCategory A—Studies in women taking levothyroxine sodium during pregnancy have not shown an increased risk of congenital abnormalities. Therefore, the possibility of fetal harm appears remote. UNITHROID (levothyroxine sodium) should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.
Hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, pre-eclampsia, stillbirth and premature delivery. Maternal hypothyroidism may have an adverse effect on fetal and childhood growth and development.
During pregnancy, serum T4 levels may decrease and serum TSH levels increase to values outside the normal range. Since elevations in serum TSH may occur as early as 4 weeks gestation, pregnant women taking UNITHROID (levothyroxine sodium) should have their TSH measured during each trimester. An elevated serum TSH level should be corrected by an increase in the dose of UNITHROID (levothyroxine sodium) . Since postpartum TSH levels are similar to preconception values, the UNITHROID (levothyroxine sodium) dosage should return to the pre-pregnancy dose immediately after delivery. A serum TSH level should be obtained 6-8 weeks postpartum.
Thyroid hormones do not readily cross the placental barrier; however, some transfer does occur as evidenced by levels in cord blood of athyroceotic fetuses being approximately one-third maternal levels. Transfer of thyroid hormone from the mother to the fetus; however, may not be adequate to prevent in utero hypothyroidism.
Nursing Mothers—Although thyroid hormones are excreted only minimally in human milk, caution should be exercised when UNITHROID (levothyroxine sodium) is administered to a nursing woman. However, adequate replacement doses of levothyroxine are generally needed to maintain normal lactation.
The goal of treatment in pediatric patients with hypothyroidism is to achieve and maintain normal intellectual and physical growth and development.
The initial dose of levothyroxine varies with age and body weight (see DOSAGE AND ADMINISTRATION, Table 3). Dosing adjustments are based on an assessment of the individual patients clinical and laboratory parameters (see PRECAUTIONS, Laboratory Tests).
In children in whom a diagnosis of permanent hypothyroidism has not been established, it is recommended that levothyroxine administration be discontinued for a 30-day trial period, but only after the child is at least 3 years of age. Serum T4 and TSH levels should then be obtained. If the T4 is low and the TSH high, the diagnosis of permanent hypothyroidism is established, and levothyroxine therapy should be reinstituted. If the T4
and TSH are normal, euthyroidism may be assumed and, therefore, the hypothyroidism can be considered to have been transient. In this instance, however, the physician should carefully monitor the child and repeat the thyroid function tests if any signs or symptoms of hypothyroidism develop. In this setting, the clinician should have a high index of suspicion of relapse. If the results of the levothyroxine withdrawal test are inconclusive, careful follow-up and subsequent testing will be necessary.
Since some more severely affected children may become clinically hypothyroid when treatment is discontinued for 30 days, an alternate approach is reduce the replacement dose of levothyroxine by half during the 30-day trial period. If, after 30 days, the serum TSH is elevated above 20 mU/L, the diagnosis permanent hypothyroidism is confirmed and full replacement therapy should be resumed. However, if the serum TSH has not risen to greater than 20 mU/L, levothyroxine treatment should be discontinued for another 30-day trial period followed by repeat serum T4 and TSH.
The presence of concomitant medical conditions should be considered in certain clinical circumstances and, if present, appropriately treated (see PRECAUTIONS).
Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism on intellectual development as well as on overall physical growth and maturation. Therefore, UNITHROID (levothyroxine sodium) therapy should be initiated immediately upon diagnosis and is generally continued for life.
During the first 2 weeks of UNITHROID (levothyroxine sodium) therapy, infants should be closely monitored for cardiac overload, arrhythmias, and aspiration from avid suckling.
The patient should be monitored closely to avoid undertreatment or overtreatment. Undertreatment may have deleterious effects on intellectual development and linear growth. Overtreatment has been associated with craniosynostosis in infants, and may adversely affect the tempo of brain maturation and accelerate the bone age with resultant premature closure of the epiphyses and compromised adult stature.
Acquired Hypothyroidism in Pediatric Patients
The patient should be monitored closely to avoid undertreatment and overtreament. Undertreatment may result in poor school performance due to impaired concentration and slowed mentation and in reduced adult height. Overtreatment may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature.
Treated children may manifest a period of catch-up growth, which may be adequate in some cases to normalize adult height. In children with severe or prolonged hypothyroidism, catch-up growth may not be adequate to normalize adult height.
Because of the increased prevalence of cardiovascular disease among the elderly, levothyroxine therapy should not be initiated at the full replacement dose (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Read the Unithroid Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/10/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Unithroid Information
Unithroid - User Reviews
Unithroid User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
Find out what women really need.