What are the potential interactions with Synthroid (levothyroxine) and other medications?

Potential Interactions with Synthroid (Levothyroxine)

Synthroid (levothyroxine) has numerous significant drug interactions that can affect its absorption, metabolism, and clinical efficacy, potentially leading to either hypothyroidism or hyperthyroidism depending on the interaction. Understanding these interactions is critical for optimal thyroid management and patient outcomes.

Major Categories of Interactions

1. Medications That Decrease Levothyroxine Absorption

• Bile Acid Sequestrants:

  • Cholestyramine, colestipol, colesevelam significantly reduce levothyroxine absorption 1
  • Recommendation: Administer levothyroxine at least 4 hours prior to these medications 2

• Minerals and Antacids:

  • Calcium supplements (carbonate, citrate, acetate)
  • Iron supplements (especially ferrous sulfate)
  • Aluminum-containing antacids
  • Recommendation: Separate administration by at least 4 hours 2

• Other Absorption Inhibitors:

  • Phosphate binders (sevelamer, lanthanum)
  • Sucralfate
  • Orlistat
  • Proton pump inhibitors (reduce gastric acidity needed for absorption) 2, 3
  • Chromium supplements 4

2. Food and Beverages Affecting Absorption

• Coffee significantly reduces levothyroxine absorption 5, 6
• Soy products may interfere with absorption 7
• High-fiber foods can reduce bioavailability 5
• Recommendation: Take levothyroxine on an empty stomach, at least 30-60 minutes before eating or drinking anything other than water

3. Medications Affecting Thyroid Hormone Transport

• Drugs that increase Thyroxine-Binding Globulin (TBG):

  • Estrogens and estrogen-containing contraceptives
  • Tamoxifen
  • Methadone
  • 5-Fluorouracil
  • Effect: May require increased levothyroxine dose 2

• Drugs that decrease TBG:

  • Androgens/anabolic steroids
  • Glucocorticoids
  • Effect: May require decreased levothyroxine dose 2

4. Medications Affecting Metabolism

• Enzyme Inducers (increase levothyroxine clearance):

  • Phenytoin
  • Carbamazepine
  • Rifampin
  • Phenobarbital
  • Effect: May require increased levothyroxine dose 1, 2

• Enzyme Inhibitors:

  • Amiodarone (also has direct effects on thyroid function)
  • Imatinib and other tyrosine kinase inhibitors 1
  • Effect: May require decreased levothyroxine dose

5. Special Clinical Situations

• Adrenal Insufficiency: Thyroid hormone increases metabolic clearance of glucocorticoids. Always treat adrenal insufficiency with glucocorticoids before starting levothyroxine to prevent acute adrenal crisis 2

• Diabetes: Addition of levothyroxine may worsen glycemic control, requiring adjustment of antidiabetic medications 2

• Anticoagulants: Levothyroxine may enhance the effects of warfarin, requiring more frequent INR monitoring 1, 2

Practical Management Approaches

1. Timing of Administration:

   • Take levothyroxine consistently at the same time each day
   • Morning and bedtime administration are equally effective if timing is consistent 7
   • Take on empty stomach, 30-60 minutes before food/other medications

2. Monitoring Recommendations:

   • Monitor TSH and free T4 levels 4-6 weeks after starting any potentially interacting medication
   • More frequent monitoring may be needed when starting or stopping interacting medications

3. Dose Adjustments:

   • When adding an interacting medication, anticipate potential need for levothyroxine dose adjustment
   • For medications that decrease absorption, consider separating administration times first before adjusting dose

Special Considerations

• Gastrointestinal Disorders: Conditions like celiac disease, H. pylori infection, and atrophic gastritis can impair levothyroxine absorption 5, 6

• Tyrosine Kinase Inhibitors: Monitor thyroid function closely when using imatinib or sunitinib, as these can cause hypothyroidism through unclear mechanisms 1

• Novel Formulations: Liquid or soft gel formulations may be less affected by some food and drug interactions 7

Remember that the magnitude of these interactions varies among patients. Regular monitoring of thyroid function tests is essential when starting, stopping, or changing doses of medications that interact with levothyroxine.