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

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.

Table 3: Drugs That May Alter T₄ and Triiodothyronine (T₃) Serum Transport Without Effecting Free Thyroxine (FT₄) Concentration (Euthyroidism)

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.

 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.

Antidiabetic Therapy

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.

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 TIROSINT dose is increased. Coagulation tests should be closely monitored to permit appropriate and timely dosage adjustments.

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.

Antidepressant Therapy

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.

Ketamine

Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended.

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.

Tyrosine-Kinase Inhibitors

Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. TSH levels should be closely monitored in such patients.

Drug-Food Interactions

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.

Last reviewed on RxList: 3/14/2012
This monograph has been modified to include the generic and brand name in many instances.