"The U.S. Food and Drug Administration today granted approval to Lenvima (lenvatinib) to treat patients with progressive, differentiated thyroid cancer (DTC) whose disease progressed despite receiving radioactive iodine therapy (radioactive iodine"...
Common adverse reactions with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage [See 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 (GI): diarrhea, vomiting, abdominal cramps, elevations in liver function tests
- Dermatologic: hair loss, flushing
- Endocrine: decreased bone mineral density
- Reproductive: menstrual irregularities, impaired fertility
Adverse Reactions in Children
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.
Hypersensitivity reactions to inactive ingredients (in this product or other levothyroxine products) 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 Tirosint (levothyroxine sodium capsules) Side Effects Center for a complete guide to possible side effects
Drugs Known to Affect Thyroid Hormone Pharmacokinetics
Many drugs affect thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to TIROSINT. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs.
A listing of drug interactions with L-thyroxine (T4) is provided in the following tables. These tables should not be seen as 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., prescribing information of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.
Table 2: Drugs That May Decrease T4 Absorption
(Hypothyroidism). Potential impact: Concurrent use may reduce the
efficacy of levothyroxine by binding and delaying or preventing absorption,
potentially resulting in hypothyroidism.
|Drug or Drug Class||Effect|
|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.|
|Orlistat||Patients treated concomitantly with orlistat and levothyroxine should be monitored for changes in thyroid function.|
|Bile Acid Sequestrants
Ion Exchange Resins
|Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer levothyroxine at least 4 hours prior to these drugs or monitor thyrotropin-stimulating hormone (TSH) levels.|
- Aluminum & Magnesium Hydroxides
Table 3: Drugs That May Alter T4
and Triiodothyronine (T3) Serum Transport Without Effecting Free Thyroxine (FT4)
|Drugs That May Increase Serum Thyroxine-Binding Globulin (TBG) Concentration||Drugs That May Decrease Serum TBG Concentration|
Estrogen-containing oral contraceptives
Estrogens (oral) Heroin / Methadone
|Androgens / Anabolic Steroids
Slow-Release Nicotinic Acid
|Drugs That May Cause Protein-Binding Site Displacement
Potential impact: 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 patients are likely clinically euthyroid.
|Salicylates ( > 2 g/day)||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%.|
Furosemide (> 80 mg IV)
Non-Steroidal Anti-inflammatory Drugs
Table 4: Drugs That May Alter
Hepatic Metabolism of T4 (Hypothyroidism). >Potential impact: Stimulation of hepatic microsomal
drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine,
resulting in increased levothyroxine requirements.
|Drug or Drug Class||Effect|
|Carbamazepine Hydantoins||Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total and FT4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Close monitoring of thyroid hormone parameters is recommended.|
Table 5: Drugs That May
Decrease Conversion of T4 to T3. Potential
impact: 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.
|Drug or Drug Class||Effect|
|Beta-adrenergic antagonists (e.g., Propranolol > 160 mg/day)||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.|
|Glucocorticoids (e.g., Dexamethasone > 4 mg/day)||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).|
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.
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 TIROSINT dose is increased. Coagulation tests should be closely monitored to permit appropriate and timely dosage adjustments.
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.
Concurrent use of tricyclic (e.g., Amitriptyline) or tetracyclic (e.g., Maprotiline) 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 central nervous system stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.
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.
Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. TSH levels should be closely monitored in such patients.
Consumption of certain foods may affect levothyroxine sodium absorption thereby necessitating adjustments in dosing. Soybean flour, 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. Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/14/2012
Additional Tirosint Information
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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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