Real world clinical experience with a new formulation of levothyroxine engineered to meet new and stricter regulatory requirements

Abstract

Objectives A new LT4 formulation (Euthyrox [LT4 NF]) was developed to meet new regulatory standards, and has replaced the older formulation (LT4 OF) in a number of countries. We evaluated the possibility of tolerability/safety concerns associated with the switch by analysing spontaneous adverse event (AE) reports before and after switching. Methods We examined spontaneous reports of adverse events (AE) from 18 countries generated from individual case safety reports (ICSRs) submitted to the pharmaceutical sponsor’s global safety database, over one year before/one year after the switch. Results There was no clear pattern relating to the numbers of ICSRs received before and after the switch across the countries. ICSRs contained a total of 634 AE relating to thyroid imbalance (82 serious) with LT4 OF over the period of one year; 343 such AE (60 serious) were reported for LT4 NF. The most common thyroid imbalance AE for LT4 OF concerned hypothyroidism or hyperthyroidism, unspecified thyroid function test abnormalities, and dosing issues. More AE of any aetiology were reported for LT4 NF (5098) vs. LT4 OF (4439), although the number of serious AE was lower for LT4 NF vs. LT4 OF (457 and 580, respectively). Fatigue, dizziness, headache, palpitations, and nausea were among the most common AE reported for each formulation. The nature of AE was comparable between formulations. Conclusions No new safety concerns arose concerning the updated LT4 formulation in the 18 countries. Careful counselling of patients and adherence to routine thyroid care is important.