Pharmacokinetics and Clinical Implications of Two Non-Tablet Oral Formulations of L-Thyroxine in Patients with Hypothyroidism.

BACKGROUND

Increased knowledge of the pharmacokinetic characteristics of orally administered levothyroxine (L-T) has improved individualization of dosing regimens. However, up to 40-45% of patients, depending on the leading cause of hypothyroidism, are still over- or, more often, undertreated. Unintentional non-adherence to L-T replacement therapy includes all situations of unintended drug-drug and drug-food interactions as well as fasting conditions that are not necessarily respected by patients.

RESULTS

In this specific context, the overall information concerning those factors with the potential to affect L-T absorption refers only to tablet formulation. Indeed, this is the reason why new non-tablet formulations of L-T were introduced some years ago. In this regard, the current literature review was designed to summarize pharmacokinetic, drug and food interactions and clinical data focusing on two new oral L-T formulations, i.e., liquid and soft-gel capsule in healthy volunteers and patients with primary hypothyroidism. The non-tablet L-T soft-gel capsules and solution have proven bioequivalence with the usual L-T tablet Princeps and generic formulations. Clinical studies have suggested higher performance of non-tablet formulations than tablet in those patients with suboptimal adherence. The impact of gastrointestinal conditions and variation of gastric pH was lower with either soft gel/solution than with tablets. In addition, the extent of drug-drug and drug-food interactions remains low and of uncertain clinical relevance.

CONCLUSIONS

Pending further studies allowing one to extend the use of soft-gel/solution preparations in unselected patients, non-tablet L-T formulations should be considered as a first-line choice, especially in those patients with moderate-to-high potential of suboptimal tablet performance.