Oral Liquid Formulation of Levothyroxine Is Stable in Breakfast Beverages and May Improve Thyroid Patient Compliance

Abstract

Patients on treatment with levothyroxine (T4) are informed to take this drug in the morning, at least 30 min before having breakfast. A significant decrease of T4 absorption was reported, in fact, when T4 solid formulations are taken with food or coffee. According to preliminary clinical study reports, administration of T4 oral solution appears to be less sensitive to the effect of breakfast beverages on oral bioavailability. In the present study, stability of T4 oral solution added to breakfast beverages was investigated. A 1 mL ampoule of single-dose Tirosint® oral solution (IBSA Farmaceutici Italia, Lodi, Italy) was poured into defined volumes of milk, tea, coffee, and coffee with milk warmed at 50 °C, as well as in orange juice at room temperature. Samples were sequentially collected up to 20 min and analyzed by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The results of the study demonstrated that T4 is stable in all beverages after 20 min incubation. Demonstration of T4 stability is a prerequisite for a thorough evaluation of the effect of breakfast beverages on the bioavailability of T4 given as oral solution and for a better understanding of the reasons underlying a decreased T4 bioavailability administered as solid formulations.

Thyroid hormonal profile in elderly patients treated with two different levothyroxine formulations: A single institute survey

“…Also our Group has recently shown that oral liquid L-T4 could diminish the problem of L-T4 malabsorption caused by coffee when using traditional tablet formulations [17]. In agreement with our data, Bernareggi et al demonstrated that liquid L-T4 is stable in many beverages for at least after 20 min incubation [18].…”

A Double-Blind Placebo-Controlled Trial of Liquid Thyroxine Ingested at Breakfast: Results of the TICO Study

“…Studies on stability carried out with tablet formulations have shown that sodium L-T4 rapidly degrades at 60-80°C (24,25); indeed, an Italian "espresso" coffee is served at similar temperatures (26). Very recently, Bernareggi et al have addressed this issue, demonstrating that liquid L-T4 is stable after 20 minutes in milk, tea, coffee, and cappuccino at 50°C, as well as in orange juice at room temperature (27).…”

Liquid levothyroxine and its potential use

“…Conversely, stability of levothyroxine liquid formulation in milk, tea, coffee with milk warmed to 50° C and orange juice at room temperature was demonstrated at up to 20 minutes of incubation, without evidence of T4 degradation in different types of matrices. 35 Recently, Cappelli et al highlighted the same results in a small group of 54 patients who wrongly consumed oral liquid L-T4 prior to breakfast within the very first few minutes or also at breakfast in their coffee. A comparable thyroid hormonal profile was obtained in patients who wrongly took L-T4 liquid formulation compared to controls who consumed it 30 min before breakfast.…”