Levothyroxine drug interactions
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Levothyroxine Drug Interactions: A Comprehensive Overview
Introduction to Levothyroxine and Its Importance
Levothyroxine is a widely prescribed medication for the treatment of hypothyroidism and the suppression of thyroid neoplasms. Given its critical role in managing thyroid hormone levels, understanding potential drug interactions is essential for ensuring its efficacy and patient safety1 8.
Medications Interfering with Levothyroxine Bioavailability
Calcium and Iron Supplements
Calcium and iron supplements are known to interfere with the absorption of levothyroxine. These supplements can form insoluble complexes with levothyroxine in the gastrointestinal tract, reducing its bioavailability1 5. To mitigate this interaction, it is recommended to separate the administration of levothyroxine and these supplements by several hours1.
Proton Pump Inhibitors and Bile Acid Sequestrants
Proton pump inhibitors (PPIs) and bile acid sequestrants can also reduce levothyroxine absorption. PPIs increase gastric pH, which can impair the dissolution and absorption of levothyroxine. Bile acid sequestrants bind to levothyroxine in the gut, preventing its absorption1 4 6. Adjusting the timing of levothyroxine administration or switching to a liquid formulation can help manage these interactions1 6.
Anticonvulsants and Sex Hormones
Anticonvulsants and sex hormones can accelerate the metabolism of levothyroxine, necessitating higher doses to maintain therapeutic levels. These drugs induce hepatic enzymes that increase the clearance of levothyroxine from the body1 4.
Ritonavir
Ritonavir, an antiretroviral medication, has been reported to interact with levothyroxine, leading to elevated thyroid-stimulating hormone (TSH) levels despite increased doses of levothyroxine. This interaction may require careful monitoring and dose adjustments of levothyroxine2.
Warfarin
Contrary to common belief, recent studies suggest that levothyroxine does not significantly potentiate the effect of warfarin. A population-based study found no meaningful increase in the risk of hemorrhage when levothyroxine was co-administered with warfarin3.
Amiodarone
Amiodarone, used for cardiac arrhythmias, can decrease the bioavailability of levothyroxine. This interaction may necessitate therapeutic drug monitoring to ensure appropriate levothyroxine levels are maintained7.
Food and Dietary Supplements Affecting Levothyroxine Absorption
Coffee, Soy, and Fiber
Certain foods and beverages, such as coffee, soy products, and high-fiber foods, can reduce the absorption of levothyroxine. These interactions are primarily due to the binding of levothyroxine to dietary components, which prevents its absorption5. It is advisable to take levothyroxine on an empty stomach and maintain a consistent routine regarding food intake5.
Calcium and Iron Supplements
As mentioned earlier, calcium and iron supplements can significantly reduce levothyroxine absorption. Maintaining a proper time interval between the intake of these supplements and levothyroxine is crucial5.
Novel Formulations
New formulations of levothyroxine, such as liquid solutions and soft-gel capsules, have been shown to mitigate the malabsorption issues caused by food and other medications. These formulations can provide more consistent absorption and improve therapeutic outcomes1 6.
Conclusion
Levothyroxine's efficacy can be significantly impacted by various medications and dietary factors. Clinicians and patients must be aware of these potential interactions to manage hypothyroidism effectively. Adjusting the timing of administration, considering alternative formulations, and closely monitoring thyroid function tests are essential strategies to optimize levothyroxine therapy. Further research is needed to provide more robust evidence and refine management guidelines for these interactions.
Sources and full results
Most relevant research papers on this topic
Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review
Many medications and foods can impair the bioavailability of levothyroxine, requiring awareness and dose adjustment for optimal treatment.
Systematic ReviewProbable interaction between levothyroxine and ritonavir: Case report and literature review.
A probable interaction between levothyroxine and ritonavir may require higher-than-usual doses of levothyroxine in patients with ritonavir-related hypothyroidism.
Case ReportA Population‐Based Assessment of the Drug Interaction Between Levothyroxine and Warfarin
Levothyroxine initiation does not increase the risk of hospitalization for hemorrhage in older patients receiving warfarin therapy.
Observational Study
Rigorous JournalDrug Interactions with Levothyroxine Therapy in Patients with Hypothyroidism: Observational Study in General Practice
Co-prescription of levothyroxine and potentially interacting drugs leads to increased use of levothyroxine, highlighting the need for careful adjustment in presence of concomitant drugs.
Non-RCT
Large Human TrialRigorous JournalLevothyroxine Interactions with Food and Dietary Supplements–A Systematic Review
Levothyroxine ingestion in the morning and at bedtime is equally effective, but interactions with coffee, soy products, fiber, calcium, or iron supplements can decrease its absorption.
Systematic ReviewDrug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care
Oral liquid levothyroxine is not associated with increased daily dosages compared to tablets during drug-drug interactions, supporting individualizing LT4 formulation prescription in patients with various comorbidities.
Observational StudyRigorous JournalIn Vivo Evaluation of the Pharmacokinetic Interaction between Levothyroxine and Amiodarone in Rat Plasma: Evaluation of Importance of Therapeutic Drug Monitoring during Co-Therapy.
The combination of levothyroxine and amiodarone significantly decreases levothyroxine bioavailability in rats, making therapeutic drug monitoring mandatory for patients receiving both medications.
Non-RCT
Animal StudyDrug Interactions That Decrease Levothyroxine Efficacy
Levothyroxine is one of the most commonly prescribed medications for the treatment of hypothyroidism as well as the suppression of thyroid neoplasms.1 Most patients with hypothyroidism require lifelong therapy with levothyroxine; therefore, the likelihood of drug interactions is high.
The drug interactions and mechanism of levothyroxine sodium with other drugs
Levothyroxine sodium's drug interactions with other drugs should be considered to prevent potential adverse effects.
Literature ReviewCiprofloxacin and rifampin have opposite effects on levothyroxine absorption.
Ciprofloxacin decreases levothyroxine absorption, while rifampin increases it, potentially causing hypothyroidism in patients on stable doses.
RCT