Do Proton Pump Inhibitors (PPIs) interact with thyroxine?

Proton Pump Inhibitors Interact with Levothyroxine and Reduce Its Absorption

Yes, proton pump inhibitors (PPIs) significantly interact with levothyroxine (thyroxine) by reducing its absorption, which can lead to elevated TSH levels and suboptimal control of hypothyroidism. This interaction has important clinical implications for patients who require both medications.

Mechanism of Interaction

The interaction between PPIs and levothyroxine occurs primarily through:

• Altered gastric pH: PPIs reduce gastric acid secretion, raising the pH of the stomach environment
• Decreased dissolution: Levothyroxine tablets require an acidic environment for proper dissolution and subsequent absorption
• Impaired absorption: The reduced acidity leads to decreased intestinal absorption of levothyroxine

Clinical Evidence of Interaction

Multiple studies confirm this interaction:

• Concomitant use of PPIs with levothyroxine leads to significant elevation in serum TSH levels in previously euthyroid patients, regardless of timing of PPI administration 1
• A systematic review found that each included study showed an increase in TSH levels following combined levothyroxine and PPI consumption, with the majority showing statistically significant increases 2
• The interaction occurs even with short-term PPI use (as little as 6 weeks) 1

Management Strategies

1. Formulation Selection

• Liquid or soft gel capsule formulations of levothyroxine are less affected by PPIs
  • A study demonstrated that switching from tablet to soft gel capsule levothyroxine corrected the impaired absorption caused by pantoprazole 3
  • Thyroidectomized patients taking PPIs who switched from conventional tablets to soft gel capsules at the same dose showed significant decreases in TSH and increases in thyroid hormone levels 4
  • A novel liquid formulation (Tirosint-SOL) has demonstrated bioequivalence with or without PPI co-administration, suggesting it may be unaffected by PPIs 5

2. Timing of Administration

• Separate administration times of levothyroxine and PPIs when possible
• The FDA drug label for levothyroxine notes that many drugs affect thyroid hormone pharmacokinetics and metabolism, emphasizing the importance of proper administration 6
• Although separating administration times may help, studies show that even evening dosing of PPIs can affect morning levothyroxine absorption 1

3. Dose Adjustment and Monitoring

• Monitor TSH levels more frequently when starting, stopping, or changing doses of PPIs in patients on levothyroxine
• Dose adjustments of levothyroxine may be necessary to maintain euthyroid status when PPIs are added or removed from the medication regimen
• The FDA recommends regular monitoring of thyroid function tests when there are changes in medication regimens that may affect levothyroxine 6

Practical Recommendations

1. For patients requiring both medications:

   • Consider using levothyroxine in soft gel capsule or liquid formulation instead of standard tablets
   • Monitor TSH levels 4-6 weeks after starting or stopping PPI therapy
   • Adjust levothyroxine dose as needed based on TSH results

2. If tablet formulation must be used:

   • Separate administration times as much as possible
   • Take levothyroxine on an empty stomach at least 30-60 minutes before breakfast
   • Consider taking PPIs at a different time of day when possible

3. For patients with persistently elevated TSH despite adequate levothyroxine dosing:

   • Evaluate for concurrent PPI use
   • Consider switching to alternative formulations of levothyroxine less affected by gastric pH

This interaction highlights the importance of considering drug-drug interactions in patients with hypothyroidism, particularly those requiring acid-suppressive therapy.