A new formulation of levothyroxine engineered to meet new specification standards

Abstract

Background: 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%).

Review: 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.

Conclusion: The new formulation, which is more stable, will assist in the accurate dosage and titration of levothyroxine in the management of hypothyroidism.

Keywords:

• Levothyroxine
• bioequivalence
• thyroid
• new formulation
• euthyrox
• specification
• shelf life
• mannitol

Acknowledgments

Medical writer Dr Mike Gwilt, GT Communications, provided editorial assistance, funded by Merck KGaA.

Notes

1 * Merck KGaA, Darmstadt, Germany.

2 * Merck KGaA, Darmstadt, Germany.