University Hospital Tübingen, Germany.
Global Medical Affairs, Merck KGaA, Darmstadt, Germany.
Curr Med Res Opin. 2019 Jan;35(1):147-150. doi: 10.1080/03007995.2018.1545635. Epub 2018 Nov 26.
Small variations in the dose of levothyroxine have been associated with marked variations in thyroid function in people with hypothyroidism. Accordingly, regulators have identified levothyroxine as a "narrow therapeutic index" drug subject to more stringent regulations compared with other drugs, in terms of the accuracy and stability of the amount of active drug in each tablet (typically required to be 95-105% of the labelled amount over its full shelf life), and its bioavailability geometric mean ratios (90% confidence intervals between 90-111.1%, including 100%). This review describes a reformulation of a widely used levothyroxine product (Euthyrox.*). The new tablet fulfils all criteria according to the new specification regulations for dosage accuracy over a shelf life of 3 years in all climate zones, and for bioequivalence compared to the conventional formulation used for many years. In addition, a clinical trial demonstrated equivalent exposure between three different tablet strengths of the new formulation, amounting to the same total dose (dose form proportionality). As a consequence, switching from the conventional to the new formulation can be undertaken on a 1:1 dose-for-dose basis, without re-titration or additional thyroid function testing. The new formulation, which is more stable, will assist in the accurate dosage and titration of levothyroxine in the management of hypothyroidism.
左甲状腺素剂量的微小变化与甲状腺功能减退症患者的甲状腺功能明显变化有关。因此，与其他药物相比，监管机构将左甲状腺素确定为一种“治疗指数较窄”的药物，在每片药物中活性药物的数量的准确性和稳定性方面（通常需要在整个保质期内达到标签数量的 95-105%），以及其生物利用度几何均数比值（90%置信区间在 90-111.1%之间，包括 100%），都受到更严格的规定。本综述描述了一种广泛使用的左甲状腺素产品（优甲乐）的重新配方。新片剂在所有气候带的 3 年保质期内满足新规格规定的剂量准确性的所有标准，并且与多年来使用的常规配方相比具有生物等效性。此外，一项临床试验表明，新配方的三种不同片剂强度之间的暴露量等效，相当于相同的总剂量（剂量形式比例）。因此，可以在不重新滴定或额外进行甲状腺功能测试的情况下，将从常规配方转换为新配方，以 1:1 的剂量比例进行转换。新配方更稳定，将有助于准确剂量和调整甲状腺功能减退症的左甲状腺素治疗。
