What drugs counteract levothyroxine (thyroid hormone replacement medication)?

Medications That Counteract Levothyroxine

Multiple medications can reduce levothyroxine effectiveness by interfering with its absorption, metabolism, or action, including bile acid sequestrants, antacids, calcium and iron supplements, and proton pump inhibitors. 1

Major Drug Classes That Interfere with Levothyroxine

1. Medications That Decrease Absorption

• Bile Acid Sequestrants

  • Cholestyramine, colestipol, colesevelam
  • Mechanism: Bind to levothyroxine in GI tract, preventing absorption
  • Recommendation: Administer levothyroxine at least 4 hours before these medications 1

• Antacids and Acid Reducers

  • Aluminum & magnesium hydroxides, proton pump inhibitors, sucralfate
  • Mechanism: Reduce gastric acidity required for levothyroxine absorption
  • Impact: Can significantly reduce bioavailability 1, 2

• Mineral Supplements

  • Calcium carbonate, ferrous sulfate, other phosphate binders
  • Mechanism: Direct binding to levothyroxine
  • Recommendation: Take levothyroxine at least 4 hours apart from these agents 1

• Other Binding Agents

  • Ion exchange resins (e.g., Kayexalate)
  • Orlistat (weight loss medication)
  • Recommendation: Monitor thyroid function when used concurrently 1

2. Medications That Alter Metabolism

• Enzyme Inducers

  • Rifampin, phenobarbital
  • Mechanism: Accelerate hepatic metabolism of levothyroxine
  • Impact: May require increased levothyroxine dosage 1, 3

• Medications That Decrease T4 to T3 Conversion

  • Beta-blockers (especially propranolol >160 mg/day)
  • Glucocorticoids
  • Impact: May alter thyroid hormone levels while TSH remains normal 1

3. Medications That Alter Protein Binding

• TBG-Increasing Drugs

  • Estrogens, oral contraceptives
  • Tamoxifen, 5-Fluorouracil
  • Heroin/Methadone
  • Impact: May increase total T4 but free T4 remains normal 1

• TBG-Decreasing Drugs

  • Androgens, anabolic steroids
  • Glucocorticoids
  • Asparaginase
  • Impact: May decrease total T4 but free T4 remains normal 1

• Protein Binding Displacers

  • Salicylates (>2g/day)
  • Furosemide (>80mg IV)
  • Carbamazepine, phenytoin
  • Heparin
  • NSAIDs (fenamates)
  • Impact: Can cause transient changes in free T4 levels 1

Clinical Management Strategies

Timing Recommendations

• For most interacting medications, separate administration from levothyroxine by at least 4 hours 1
• For bile acid sequestrants specifically, Health Canada recommends taking other drugs at least 1 hour before or 4-6 hours after these agents 4
• Gastric emptying studies suggest a 3-hour window between administration is adequate to avoid potential interactions 4

Monitoring Recommendations

• Check TSH levels 6-8 weeks after starting any potentially interacting medication 3
• Monitor for symptoms of hypothyroidism if a new medication that may interfere with levothyroxine is started

Alternative Formulations

• Liquid or soft-gel formulations may help overcome some absorption issues, particularly those related to gastric pH changes and direct binding 5, 6

Common Pitfalls and Caveats

1. Patient Awareness Gap: Many patients don't inform physicians about over-the-counter antacids or supplements they're taking 2

2. Food Interactions: Coffee, dietary fiber, soy products, and certain fruits like papaya can also reduce levothyroxine absorption 6, 7

3. Timing Issues: Morning vs. bedtime administration of levothyroxine appears equally effective, but consistency is key 7

4. Narrow Therapeutic Index: Levothyroxine has a narrow therapeutic window - both underdosage and overdosage can lead to adverse effects 8

5. Formulation Differences: Different levothyroxine products may not be bioequivalent, which can be problematic when switching between products 8

By understanding these interactions and implementing appropriate spacing between medications, most interference with levothyroxine can be effectively managed to maintain proper thyroid hormone levels.