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Drug Interactions with Levothyroxine Therapy in Patients with Hypothyroidism: Observational Study in General Practice

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Background and Objectives

Several drugs may interact with levothyroxine and reduce its bioavailability. The aim of this study was to analyse the Italian general practice patients with hypothyroidism from 2002–2011, in terms of variation of thyroid-stimulating hormone (TSH) levels, number of levothyroxine prescriptions and dose of levothyroxine before and during potential drug–drug interactions (DDIs).


Data were extracted from the Italian general practice Health Search CSD Longitudinal Patient Database (HSD). Analysis was limited to individuals aged 18 years and older with at least one levothyroxine prescription from 2002 to 2011 and at least one year of clinical history recorded in HSD. A quasi-experimental pre-post analysis was carried out using a self-controlled study design, on an intention-to-treat basis.


Overall, 5,426 levothyroxine users (7.5 % of population in HSD) were included in the study. The incidence rate ratio comparing the TSH trend before and during the period of exposure to potential DDI showed a significant increase of TSH levels during initial exposure to potential DDI, which decreased over time. The number of prescriptions and dose of levothyroxine decreased before the potential DDI and increased symmetrically during the period of exposure to potential DDI.


The co-prescription of levothyroxine and potentially interacting drugs results in an increased use of levothyroxine. Clinicians should carefully consider adjusting levothyroxine therapy in presence of concomitant drugs, such as proton-pump inhibitors, which may reduce levothyroxine bioavailability.

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Correspondence to Gianluca Trifirò.

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Trifirò, G., Parrino, F., Sultana, J. et al. Drug Interactions with Levothyroxine Therapy in Patients with Hypothyroidism: Observational Study in General Practice. Clin Drug Investig 35, 187–195 (2015).

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