Does Synthroid (levothyroxine) cause side effects?

Synthroid (levothyroxine) is a synthetic (man-made) version of the principle thyroid hormone, thyroxine (T4) made and released by the thyroid gland used to treat low thyroid (hypothyroidism) and to suppress thyroid hormone release in the management of cancerous thyroid nodules and growth of goiters. 

Thyroid hormone increases the metabolic rate of cells of all tissues in the body. In the fetus and newborn, thyroid hormone is important for the growth and development of all tissues including bones and the brain. In adults, thyroid hormone helps to maintain brain function, utilization of food, and body temperature, among other effects.

Common side effects of Synthroid include

Serious side effects of Synthroid include

Drug interactions of Synthroid include blood thinners because Synthroid may increase the effect of blood thinners. 

Initiation or discontinuation of therapy with Synthroid in diabetic patients may create a need for an increase or decrease in the required dose of insulin and/or antidiabetic drug.

Intravenous administration of epinephrine to patients with coronary artery disease may lead to complications ranging from difficulty in breathing to a heart attack. These complications may occur more frequently among patients also taking Synthroid. 

Converting a state of hypothyroidism (under activity) to a normal state (euthyroid state) with Synthroid may decrease the actions of certain beta-blocking drugs. For the same reason, the dose of digoxin also may need to be changed. 

Converting hypothyroidism to the euthyroid state with Synthroid may increase the blood level of theophylline, and it may be necessary to change the dose of theophylline. 

Taking Synthroid at the same time as calcium carbonate, ferrous sulfate, cholestyramine, or colestipol may decrease the effect of Synthroid and lead to hypothyroidism. 

Taking Synthroid one hour before or four hours after these drugs is necessary to prevent binding. 

Pregnancy may increase Synthroid requirements. 

Synthroid therapy in nursing mothers is usually safe but should be supervised by a physician. Consult your doctor before breastfeeding.

What are the important side effects of Synthroid (levothyroxine)?

Levothyroxine therapy usually is well-tolerated. If symptoms occur, they often are due to toxic levels of thyroid hormone, and the symptoms are those of hyperthyroidism.

The most commonly reported side effects include:

Synthroid (levothyroxine) side effects list for healthcare professionals

Adverse reactions associated with Synthroid therapy are primarily those of hyperthyroidism due to therapeutic overdosage. They include the following:

Seizures have been reported rarely with the institution of levothyroxine therapy.

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.

Hypersensitivity Reactions

Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

What drugs interact with Synthroid (levothyroxine)?

Drugs Known To Affect Thyroid Hormone Pharmacokinetics

Many drugs can exert effects on thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Synthroid (see Tables 2-5 below).

Table 2: Drugs That May Decrease T4 Absorption (Hypothyroidism)

Potential impact: Concurrent use may reduce the efficacy of Synthroid by binding and delaying or preventing absorption, potentially resulting in hypothyroidism.
Drug or Drug ClassEffect
Phosphate Binders (e.g., calcium carbonate, ferrous sulfate, sevelamer, lanthanum)Phosphate binders may bind to levothyroxine. Administer Synthroid at least 4 hours apart from these agents.
OrlistatMonitor patients treated concomitantly with orlistat and Synthroid for changes in thyroid function.
Bile Acid Sequestrants (e.g., colesevelam, cholestyramine, colestipol) Ion Exchange Resins (e.g., Kayexalate)Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer Synthroid at least 4 hours prior to these drugs or monitor TSH levels.
Proton Pump Inhibitors Sucralfate Antacids (e.g., aluminum & magnesium hydroxides, simethicone)Gastric acidity is an essential requirement for adequate absorption of levothyroxine. Sucralfate, antacids and proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce levothyroxine absorption. Monitor patients appropriately.

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

Drug or Drug ClassEffect
Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin / Methadone 5-Fluorouracil Mitotane TamoxifenThese drugs may increase serum thyroxine-binding globulin (TBG) concentration.
Androgens / Anabolic Steroids Asparaginase Glucocorticoids Slow-Release Nicotinic AcidThese drugs may decrease serum TBG concentration.
Potential impact (below): Administration of these agents with Synthroid results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations.
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%.
Other drugs: Carbamazepine Furosemide (> 80 mg IV) Heparin Hydantoins Non-Steroidal Anti-inflammatory Drugs - FenamatesThese drugs may cause protein-binding site displacement. Furosemide has been shown to inhibit the protein binding of T4 to TBG and albumin, causing an increase free T4 fraction in serum. Furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower the total T4 level. 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. Closely monitor thyroid hormone parameters.

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 Synthroid requirements.
Drug or Drug ClassEffect
Phenobarbital RifampinPhenobarbital has been shown to reduce the response to thyroxine. Phenobarbital increases L-thyroxine metabolism by inducing uridine 5’-diphospho-glucuronosyltransferase (UGT) and leads to a lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Rifampin has been shown to accelerate the metabolism of levothyroxine.

Table 5: Drugs That MayDecrease 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 ClassEffect
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, TSH levels remain normal, and patients are clinically euthyroid. Actions of particular beta-adrenergic antagonists may be impaired when a 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).
Other drugs: AmiodaroneAmiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, and decreased or normal free-T3) in clinically euthyroid patients.

Antidiabetic Therapy

  • Addition of Synthroid therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements.
  • Carefully monitor glycemic control, especially when thyroid therapy is started, changed, or discontinued.

Oral Anticoagulants

  • Synthroid 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 Synthroid dose is increased.
  • Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

Digitalis Glycosides

  • Synthroid may reduce the therapeutic effects of digitalis glycosides.
  • Serum digitalis glycoside levels may decrease 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 Synthroid 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.
  • Synthroid may accelerate the onset of action of tricyclics.
  • Administration of sertraline in patients stabilized on Synthroid may result in increased Synthroid requirements.

Ketamine

  • Concurrent use of ketamine and Synthroid may produce marked hypertension and tachycardia.
  • Closely monitor blood pressure and heart rate in these patients.

Sympathomimetics

  • Concurrent use of sympathomimetics and Synthroid 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. Closely monitor TSH levels in such patients.

Drug-Food Interactions

  • Consumption of certain foods may affect Synthroid absorption thereby necessitating adjustments in dosing.
  • Soybean flour, cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of Synthroid from the gastrointestinal tract.
  • Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability.

Drug-Laboratory Test Interactions

  • Consider changes in TBG concentration when interpreting T4 and T3 values. Measure and evaluate unbound (free) hormone and/or determine the free-T4 index (FT4I) in this circumstance.
  • Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentration.
  • Nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens, and corticosteroids decrease TBG concentration.
  • Familial hyper-or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

Summary

Synthroid (levothyroxine) is a synthetic (man-made) version of the principle thyroid hormone, thyroxine (T4) made and released by the thyroid gland used to treat low thyroid (hypothyroidism) and to suppress thyroid hormone release in the management of cancerous thyroid nodules and growth of goiters. Common side effects of Synthroid include chest pain, increased heart rate or pulse rate, excessive sweating, heat intolerance, nervousness, headache, insomnia, diarrhea, vomiting, weight loss, fever, and irregular menstrual cycles. Pregnancy may increase Synthroid requirements. Synthroid therapy in nursing mothers is usually safe but should be supervised by a physician.

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Medically Reviewed on 9/23/2020
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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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