Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care

Endocrine. 2018 Mar;59(3):585-592. doi: 10.1007/s12020-017-1412-4. Epub 2017 Sep 14.


Purpose: Several medications may interact with levothyroxine (LT4) intestinal absorption or metabolism, thus reducing its bioavailability. We investigated the variability of thyroid stimulating hormone (TSH) levels and prescribed daily dosages (PDDs) of LT4 before and during potential drug-drug interactions (DDIs) in users of tablets vs. oral liquid LT4 formulations.

Methods: By using the Italian general practice Health Search Database (HSD), we retrospectively selected adult patients with at least one LT4 prescription from 2012 to 2015 and at least 1 year of clinical history recorded. The incident prescription of interacting medications (e.g., proton pump inhibitors, calcium or iron salts) was the index date. Analysis was carried out using a self-controlled study design.

Results: Overall, 3965 users of LT4 formed the study cohort (84.1% women, mean age 56 ± 16.5 years). TSH variability on the entry date was greater among liquid LT4 users than in those prescribed with tablets as shown by the difference between 75th and 25th centile, which were 3.01 and 3.8, respectively. The incidence rate ratio (IRR) for TSH variability did not differ between groups, before and during exposure to DDIs. In contrast, PDDs less likely increased during the exposure to DDI with oral liquid LT4 compared with tablets (IRR = 0.84; 95% CI: 0.77-0.92), especially in patients with post-surgical hypothyroidism (IRR = 0.75; 95% CI: 0.64-0.85).

Conclusions: In clinical practice, the use of oral liquid LT4 is not associated with increased PDDs, compared with tablets formulation, during exposure to DDIs. These results support the need for individualizing LT4 formulation to prescribe, especially in patients with various comorbidities and complex therapeutic regimens.

Keywords: Drug–drug interactions; Gastrointestinal absorption; Oral liquid levothyroxine; Prescribed daily dosages; Primary care; Tablet levothyroxine.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Drug Interactions
  • Female
  • Humans
  • Hypothyroidism / drug therapy*
  • Male
  • Middle Aged
  • Primary Health Care
  • Retrospective Studies
  • Tablets
  • Thyroxine / administration & dosage*
  • Thyroxine / therapeutic use


  • Tablets
  • Thyroxine