Drug interactions with levothyroxine
Pro Research Analysisby 
Searched over 200M research papers
Common Drug Interactions with Levothyroxine: Calcium, Iron, and Proton Pump Inhibitors
Levothyroxine’s absorption and effectiveness can be significantly reduced by several commonly used medications. Calcium and iron supplements, as well as proton pump inhibitors (PPIs), are among the most frequently reported drugs that interfere with levothyroxine bioavailability. These interactions often occur through direct complexing in the gut or by altering stomach acidity, which impairs the drug’s absorption. Bile acid sequestrants, phosphate binders, sex hormones, and anticonvulsants can also reduce levothyroxine absorption or increase its metabolism, leading to suboptimal thyroid hormone levels and the need for higher doses of levothyroxine to maintain normal thyroid function 123910.
Food and Dietary Supplement Interactions with Levothyroxine
Certain foods and dietary supplements can also decrease levothyroxine absorption. Coffee, soy products, fiber, milk, juices, papaya, and enteral nutrition have all been shown to reduce the drug’s effectiveness when taken together with levothyroxine. Calcium and iron supplements, as well as aluminum- and chromium-containing preparations, are particularly notable for causing malabsorption. Conversely, vitamin C may enhance levothyroxine absorption. To minimize these interactions, it is recommended to separate the timing of levothyroxine and interfering foods or supplements, especially coffee, calcium, and iron 1910.
Drug Interactions in Special Populations: Antidepressants and Antiretrovirals
Levothyroxine can interact with certain antidepressants and antiretroviral medications. Selective serotonin reuptake inhibitors (SSRIs) like paroxetine have been associated with reduced levothyroxine effectiveness, sometimes requiring significant dose increases. In contrast, tricyclic antidepressants may not have this effect, suggesting they could be a safer choice for patients with hypothyroidism who need antidepressant therapy .
Antiretroviral drugs, especially protease inhibitors such as ritonavir and lopinavir/ritonavir, can increase the metabolism of levothyroxine, leading to persistent hypothyroidism despite escalating doses. This interaction is likely due to the induction of liver enzymes that inactivate levothyroxine. Switching to alternative antiretroviral regimens can resolve this issue, but careful monitoring is required 56.
Amiodarone and Levothyroxine: Cardiac Drug Interactions
Amiodarone, a medication used for cardiac arrhythmias, can also interact with levothyroxine. Co-administration has been shown to decrease levothyroxine bioavailability and increase its clearance, which may contribute to hypothyroidism in patients receiving both drugs. Regular monitoring of thyroid function is recommended for patients on this combination .
Impact of Gastrointestinal Disorders and Other Factors
Gastrointestinal conditions such as celiac disease, atrophic gastritis, lactose intolerance, and Helicobacter pylori infection can impair levothyroxine absorption. Treating these conditions and monitoring thyroid function is important to avoid under- or overtreatment. The effect of dietary fiber and some other medications (e.g., orlistat, polystyrene sulfonate, raloxifene, simethicone) on levothyroxine absorption is less clear and requires further research .
Levothyroxine Formulations: Tablets vs. Liquid and Soft-Gel Capsules
Switching from tablet to liquid or soft-gel capsule formulations of levothyroxine can help overcome absorption issues caused by drug or food interactions. Liquid and soft-gel forms are less affected by chelation and changes in stomach acidity, making them a good option for patients with persistent absorption problems or those taking multiple interacting medications 1710.
Clinical Recommendations and Management
To manage drug and food interactions with levothyroxine, clinicians should:
- Separate the timing of levothyroxine and interfering substances (e.g., take levothyroxine on an empty stomach and wait at least 30–60 minutes before eating or taking other medications).
- Consider switching to liquid or soft-gel formulations if absorption issues persist.
- Monitor thyroid-stimulating hormone (TSH) and free T4 levels regularly, especially when starting or stopping interacting drugs.
- Adjust levothyroxine doses as needed when new medications are introduced or discontinued 1237910.
Conclusion
Levothyroxine is highly susceptible to interactions with a wide range of medications, foods, and supplements, which can significantly reduce its absorption and effectiveness. Awareness of these interactions and appropriate management strategies—such as dose adjustments, timing separation, and alternative formulations—are essential to ensure optimal thyroid hormone replacement and patient outcomes. Regular monitoring and individualized therapy are key, especially in patients with complex medication regimens or underlying gastrointestinal disorders.
Sources and full results
Most relevant research papers on this topic