Background: Levothyroxine (LT4) as a medication is used by up to 5.3% of the adult
population. For optimal efficacy, the traditional tablet formulation (LT4tab) requires
that patients avoid concomitant ingestion with food, drinks, and certain medications,
as well as excellent patient compliance. Some comorbidities influence bioavailability
of LT4 and may mandate repeated dose adjustments.
Summary: New LT4 formulations (soft gel [LT4soft] and liquid [LT4liq]) containing
predissolved LT4 are claimed to improve bioavailability, presumably by facilitating
absorption. Thus, these formulations may well be more suitable than LT4tab for patients
whose daily requirements are subjected to variations in bioavailability. Here, we
review the evidence and indications for use of new LT4 formulations and highlight
areas of uncertainty that are worthy of further investigation. While bioequivalence
is established for LT4soft and LT4liq administered to healthy volunteers compared
with LT4tab in pharmacokinetic (PK) studies, therapeutic equivalence of the new formulations
seems to be different in several clinical settings. Some evidence suggests that new
formulations of LT4 may mitigate against the strict requirements relating to concomitant
ingestion with food, drinks, and certain medications, which apply to traditional LT4
tablets. The principal indication is in selected patients with disease fluctuations
and intermittent therapies with interfering medications, where the need for frequent
dose adjustments and office visits may be diminished. Whether the use of LT4soft or
LT4liq in patients with impaired gastric acid secretion results in better control
of hypothyroidism than LT4tab remains unclear.
Conclusions: The evidence in favor of using LT4soft and LT4liq in clinical practice
over LT4tab is weak, and the underlying putative PK mechanisms unclear. Additional
studies to investigate these potential benefits, define the cost-effectiveness, and
understand the PK mechanisms involved with new LT4 formulations are needed.
