May 25, 2017
Recommended Topic Related To:


"The US Food and Drug Administration (FDA) has approved calcifediol (Rayaldee, Opko Health, Inc) for the treatment of adults with secondary hyperparathyroidism (SHPT) associated with vitamin D insufficiency (serum total 25-hydroxyvitamin D "...



Side Effects


Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage (see PRECAUTIONS and OVERDOSAGE). They include the following:

General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating;

Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia;

Musculoskeletal: tremors, muscle weakness;

Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest;

Respiratory: dyspnea;

Gastrointestinal: diarrhea, vomiting, abdominal cramps and elevations in liver function tests;

Dermatologic: hair loss, flushing;

Endocrine: decreased bone mineral density; Reproductive: menstrual irregularities, impaired fertility.

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in children with resultant compromised adult height.

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 GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

Read the Levothroid (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 LEVOTHROID® (levothyroxine sodium) . In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions 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

Drugs that may reduce TSH secretion - the reduction is not sustained;therefore,hypothyroidism does not occur
Drug or Drug Class
Dopamine / Dopamine Agonists Glucocorticoids Octreotide
Effect - Use of these agents may result in a transient reduction in TSH secretion when administered at the following doses:Dopamine ( ≥ 1µ g/kg/min); Glucocorticoids (hydrocortisone ≥ 100 mg/day or equivalent);Octreotide ( > 100 µg/day).
Drugs that alter thyroid hormone secretion
Drugs that may decrease thyroid hormone secretion,which may result in hypothyroidism
Drug or Drug Class
Aminoglutethimide Iodide Methimazole
Amiodarone (including iodine-containing Radiographic contrast agents) Lithium Propylthiouracil (PTU) Sulfonamides Tolbutamide
Effect - 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., Hashimoto's thyroiditis or with Grave's disease previously treated with radioiodine or surgery) are among those individuals who are particularly susceptible to iodine-induced hypothyroidism. Oral chole-cystographic 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
Drug or Drug Class
Iodide (including iodine-containing Radiographic contrast agents)
Effect - Iodide and drugs that contain pharmacological amounts of iodide may cause hyperthyroidism in euthyroid patients with Grave's 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 hyper-thyroidism by causing thyroiditis.
Drugs that may decrease T4 absorption,which may result in hypothyroidism
Drug or Drug Class
Antacids Bile Acid Sequestrants Cation Exchange Resins
- Aluminum & Magnesium - Cholestyramine - Kayexalate
Hydroxides - Colestipol Ferrous Sulfate
- Simethicone Calcium Carbonate Sucralfate
Effect - Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or preventing absorption, potentially resulting in hypothy-roidism.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 - but FT 4 concentration remains normal;and,therefore,the patient remains euthyroid
Drugs that may increase serum TBG concentration
Clofibrate Estrogens (oral) Mitotane
Estrogen-containing Heroin /Methadone Tamoxifen
Oral contraceptives 5-Fluorouracil  
Drugs that may decrease serum TBG concentration
Androgens / Anabolic Steroids Glucocorticoids  
Asparaginase Slow-Release Nicotinic Acid  
Drugs that may cause protein-binding site displacement
Drug or Drug Class
Furosemide ( > 80 mg IV) Non Steroidal Anti-Inflammatory Drugs  
Heparin - Fenamates  
Hydantoins - Phenylbutazone  
  Salicylates ( > 2 g/day)  
Effect - 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
Drug or Drug Class
Carbamazepine Hydantoins Phenobarbital Rifampin
Effect - Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements. Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total- and free-T4 may bereduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid.
Drugs that may decrease T4 5'-deiodinase activity
Drug or Drug Class    
Beta-adrenergic antagonists Glucocorticoids  
- (e.g., Propranolol > 160 mg/day) - (e.g., Dexamethasone ≥ 4 mg/day) Propylthiouracil (PTU)  
Effect - Administration of these enzyme inhibitors decreases the peripheral conversion of T4 to T3, leading 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 ofparticular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state.Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels.However, long-term glucocor-ticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (see above).
Drug or Drug Class
Anticoagulants (oral)    
- Coumarin Derivatives - Indandione Derivatives  
Effect - 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.
Drug or Drug Class
- Tricyclics (e.g., Amitriptyline) - Selective Serotonin Reuptake Inhibitors  
- Tetracyclics (e.g., Maprotiline) (SSRIs;e.g., Sertraline)  
Effect - 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.
Drug or Drug Class
Antidiabetic Agents - Meglitinides - Sulfonylureas
- Biguanides - Thiazolidinediones - Insulin
Effect - 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.
Drug or Drug Class
Cardiac Glycosides    
Effect - Serum digitalis glycoside levels may be reduced in hyperthyroidism or when the hypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalis glycosides may be reduced.
Drug or Drug Class
Cytokines - Interferon-α - Interleukin-2
Effect - Therapy with interferon-α 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-β and -γ have not been reported to cause thyroid dysfunction.
Drug or Drug Class
Growth Hormones - Somatrem - Somatropin
Effect - Excessive use of thyroid hormones with growth hormones may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to growth hormone.
Drug or Drug Class
Effect - Concurrent use may produce marked hypertension and tachycardia;cautious administration to patients receiving thyroid hormone therapy is recommended.
Drug or Drug Class
Methylxanthine Bronchodilators - (e.g., Theophylline)  
Effect - Decreased theophylline clearance may occur in hypothyroid patients; clearance returns to normal when the euthyroid state is achieved.
Drug or Drug Class
Radiographic Agents    
Radiographic Agents
Effect - Thyroid hormones may reduce the uptake of 123I, 131I, and 99mTc.
Drug or Drug Class
Effect - 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.
Drug or Drug Class
Chloral Hydrate Metoclopramide Perphenazine
Diazepam 6-Mercaptopurine Resorcinol
Ethionamide Nitroprusside (excessive topical use)
Lovastatin Para-aminosalicylate sodium Thiazide Diuretics
Effect - These agents have been associated with thyroid hormone and / or TSH level alterations by various mechanisms.

Oral anticoagulants

Levothyroxine 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 LEVOTHROID® (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 GI 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.

Read the Levothroid Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 1/26/2017

Side Effects

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