Levo-T
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 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 Levo-T (levothyroxine sodium tablets) Side Effects Center for a complete guide to possible side effects »
DRUG INTERACTIONS
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 Levo-T™ (levothyroxine sodium tablets) . 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 | Effect |
| 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 ( ≥ 1 mcg/kg/min); Glucocorticoids (hydrocortisone ≥ 100 mg/day or equivalent); Octreotide ( > 100 mcg/day). |
| Drugs that alter thyroid hormone secretion | |
| Drugs that may decrease thyroid hormone secretion, which may result in hypothyroidism | |
| Aminoglutethimide Amiodarone Iodide (including iodine-containing Radiographic contrast agents) Lithium Methimazole Propylthiouracil (PTU) Sulfonamides Tolbutamide |
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 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 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 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 - but FT4 concentration remains normal;and, therefore, the patient remains euthyroid | |
| 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 Asparaginase Glucocorticoids Slow-Release Nicotinic Acid |
| Drugs that may cause protein-binding site displacement | |
| Furosemide ( > 80 mg IV) Heparin Hydantoins Non Steroidal Anti-Inflammatory 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 | |
| Carbamazepine Hydantoins Phenobarbital Rifampin |
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 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 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 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 glucocorticoids 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). |
| Miscellaneous | |
| Anticoagulants (oral) -Coumarin Derivatives -Indandione Derivatives |
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. |
| Antidepressants -Tricyclics (e.g., Amitriptyline) -Tetracyclics (e.g., Maprotiline) -Selective Serotonin Reuptake Inhibitors (SSRIs; e.g., Sertraline) |
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 trycyclics 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. |
| Cardiac Glycosides | Serum digitalis glycoside levels may be reduced in hyperthyroidism or when a hypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalis glycosides may be reduced. |
| Cytokines -Interferon-α -Interleukin-2 |
Therapy with interferon-a 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. |
| Growth Hormones -Somatrem -Somatropin |
Excessive use of thyroid hormones with growth hormones may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to growth hormone. |
| Ketamine | Concurrent use may produce marked hypertension and tachycardia; cautious administration to patient receiving thyroid hormone therapy is recommended. |
| Methylxanthine Bronchodilators -(e.g., Theophylline) | Decrease theophylline clearance may occur in hypothyroid patients; clearance returns to normal when the euthyroid state is achieved. |
| Radiographic Agents | Thyroid hormones may reduce the uptake of 123I, 131I, and99m Tc. |
| Sympathomimetics | 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. |
| Chloral Hydrate Diazepam Ethionamide Lovastatin Metoclopramide 6-Mercaptopurine Nitroprusside Para-aminosalicylate sodium Perphenazine Resorcinol (excessive topical use) Thiazide Diuretics |
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 Levo-T™ (levothyroxine sodium tablets) 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.
Last reviewed on RxList: 7/10/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Levo-T Information
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