Levothyroxine Use in Infants and Children with Congenital or Acquired Hypothyroidism

Contributing Editor: Marcia L. Buck, Pharm.D.; Editorial Board: Kristi N. Hofer, Pharm.D.; Michelle W. McCarthy, Pharm.D.


Pediatr Pharm. 2008;14(10) 

In This Article

Drug Interactions

There is a long list of drugs that may affect the pharmacokinetics of levothyroxine or its function. In addition, levothyroxine can have a significant impact on many other drugs. Parents of children receiving levothyroxine should be aware of the need to discuss any new prescription or over-the-counter medication, nutritional supplement, or herbal product with their child's health care provider to identify any potential interactions.[2,3]

Several drugs can reduce the oral absorption of thyroid hormones. Oral levothyroxine should be taken at least 4 hours apart from the following agents: antacids containing aluminum or magnesium, calcium carbonate, ferrous sulfate, simethicone, cholestyramine, colestipol, sucralfate, orlistat, or sodium polystyrene sulfonate (Kayexalate®). Drugs affecting protein binding may also alter the effectiveness of levothyroxine. Clofibrate, oral estrogens, methadone, 5-flurouracil, mitotane, and tamoxifen may increase serum TBG, while anabolic steroids, asparaginase, glucocorticoids, and nicotinic acid decrease TBG concentrations. Concurrent administration of levothyroxine and furosemide, heparin, phenytoin, or non-steroidal anti-inflammatory agents may result in displacement of levothyroxine from its protein binding sites, increasing free T4 levels.[2,3]

Carbamazepine, phenytoin, phenobarbital, and rifampin, increase the metabolism of levothyroxine and may reduce T4 concentrations by up to 40%. The extent of this effect varies, and dosage adjustment should be guided by thyroid function studies. Several drugs decrease the rate of deiodination of levothyroxine. These agents, amiodarone, beta-adrenergic antagonists, glucocorticoids, and propylthiouracil, may produce only a minimal change in T4, but result in significant reductions in T3 levels.[2,3]

Administration of levothyroxine may alter the effects of other drugs. Thyroid hormones increase the catabolism of vitamin-K dependent clotting factors, so that patients receiving warfarin may have an increased pharmacologic response. Warfarin doses should be adjusted to maintain target prothrombin time values and minimize the risk for bleeding.[2,3]

Concomitant use of levothyroxine and selective serotonin reuptake inhibitors, tricyclic, or tetracyclic antidepressants may result in an increased risk of toxicity from both drugs. Use of levothyroxine with antidiabetic drugs or insulin may decrease their effect. Dosage adjustment may be necessary to maintain desired serum glucose levels. The effect of digoxin may be reduced by administration of levothyroxine. Use of levothyroxine with sympathomimetic drugs may increase the effect of either drug. Use of ketamine with levothyroxine may produce hypertension and tachycardia. Levothyroxine may also reduce the uptake of radiographic agents, including 123I, 131I, and 99mTc.[2,3]

Use of thyroid hormones with growth hormone may cause premature epiphyseal closure. Patients requiring this combination should be closely monitored for growth and bone formation. Other drugs have been reported to interact with exogenous thyroid hormones, but the mechanism for the reaction has not been clearly established. These drugs: chloral hydrate, diazepam, ethionamide, lovastatin, metoclopramide, 6-mercaptopurine, nitroprusside, para-aminosalicylate sodium, perphenazine, resorcinol, and thiazide diuretics, should be used with caution in patients being treated with levothyroxine.[2,3]

In addition to these drug interactions, there are several drugs that can produce a transient hypothyroidism, resulting in the need for initiating levothyroxine or dosage adjustment in patients already on therapy. Drugs that reduce TSH secretion, such as dopamine or dopamine agonists, glucocorticoids, and octreotide, may produce a temporary reduction in endogenous thyroid hormone production. Likewise, a reduction in T3 and T4 may be seen with use of aminoglutethimide, lithium, methimazole, propylthiouracil, sulfonamides, and tolbutamide. Amiodarone and iodide administration may produce either hypo- or hyperthyroidism.[2,3,14]


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