What are the potential drug interactions with Levothyroxine (thyroid hormone replacement medication)?

Potential Drug Interactions with Levothyroxine

Levothyroxine has numerous clinically significant drug interactions that can affect its absorption, metabolism, and efficacy, requiring careful medication timing and dose adjustments to maintain optimal thyroid function.

Key Drug Interactions Affecting Absorption

• Medications that bind to levothyroxine in the gastrointestinal tract can significantly reduce absorption:

  • Calcium supplements: Separate administration by at least 4 hours 1
  • Iron supplements: Administer levothyroxine at least 4 hours apart 1, 2
  • Antacids containing aluminum & magnesium hydroxides: Can reduce absorption by affecting gastric acidity 1
  • Phosphate binders (calcium carbonate, ferrous sulfate, sevelamer, lanthanum): Bind to levothyroxine and delay absorption 1
  • Bile acid sequestrants (colesevelam, cholestyramine, colestipol): Administer levothyroxine at least 4 hours prior to these medications 1, 3

• Medications affecting gastric pH can impair levothyroxine absorption:

  • Proton pump inhibitors: Reduce gastric acidity required for optimal absorption 1, 3
  • Sucralfate: Affects intragastric pH and reduces absorption 1
  • H2-receptor antagonists: May affect absorption, though evidence is contradictory 3

Food and Beverage Interactions

• Coffee: Significantly reduces levothyroxine absorption; separate administration by at least 1 hour 4, 5
• Dietary fiber: May impair absorption, though the effect is not fully understood 4, 3
• Soy products: Can decrease levothyroxine absorption 4, 5
• Calcium-rich foods and milk: Interfere with absorption 4
• Vitamin C: May enhance levothyroxine absorption 4, 3

Medications Affecting Thyroid Hormone Transport and Metabolism

• Medications that increase thyroxine-binding globulin (TBG) concentration:

  • Estrogen-containing oral contraceptives
  • Estrogens (oral)
  • Heroin/Methadone
  • Tamoxifen
  • Clofibrate
  • 5-Fluorouracil
  • Mitotane 1

• Medications that decrease TBG concentration:

  • Androgens/Anabolic steroids
  • Asparaginase
  • Glucocorticoids
  • Slow-release nicotinic acid 1

• Medications that displace thyroid hormones from protein binding sites:

  • Salicylates (>2g/day)
  • Carbamazepine
  • Furosemide (>80 mg IV)
  • Heparin
  • Hydantoins
  • Non-steroidal anti-inflammatory drugs (fenamates) 1

Tyrosine Kinase Inhibitors and Thyroid Function

• Imatinib and Sunitinib: Associated with hypothyroidism; mechanism unclear 6
• Patients on these medications should have thyroid function evaluated regularly 6

Endocrine and Metabolic Interactions

• Adrenal insufficiency: Thyroid hormone increases metabolic clearance of glucocorticoids. Initiate glucocorticoid therapy before starting levothyroxine to prevent acute adrenal crisis 1

• Diabetes mellitus: Addition of levothyroxine may worsen glycemic control and increase antidiabetic agent or insulin requirements 1

• Raloxifene: May decrease levothyroxine absorption when administered concomitantly; separate administration by 12 hours 7, 3

Clinical Management Strategies

• Timing of administration is critical:

  • Take levothyroxine on an empty stomach, 30-60 minutes before breakfast 4
  • Bedtime administration is an acceptable alternative 4
  • Maintain consistent timing of administration relative to meals and other medications 2, 4

• Monitoring recommendations:

  • Check TSH levels 6-8 weeks after starting potentially interacting medications 8
  • Monitor more frequently in patients with multiple medications 6
  • For patients with hypothyroidism on immunotherapy, careful monitoring is essential as immune checkpoint inhibitors can cause thyroid dysfunction 6

• Alternative formulations:

  • Liquid or soft-gel formulations may help overcome some absorption issues related to coffee, calcium, and iron 2, 5
  • These formulations represent an effective approach for patients with impaired absorption 5

Special Considerations

• Patients with gastrointestinal disorders (celiac disease, atrophic gastritis, H. pylori infection) may have impaired levothyroxine absorption 3

• Patients with liver dysfunction should be monitored more closely due to potential drug interactions 6

• Pregnancy: Levothyroxine requirements often increase during pregnancy, requiring more frequent monitoring 8

• Elderly patients or those with cardiac disease: Start with lower doses (25-50 mcg/day) and titrate gradually to avoid cardiac complications 8

By understanding these interactions and implementing appropriate management strategies, clinicians can optimize levothyroxine therapy and maintain euthyroidism in patients requiring thyroid hormone replacement.