Different Formulations of Levothyroxine for Treating Hypothyroidism: A Real-Life Study

Abstract

Objective. Hypothyroid patients are treated by sodium levothyroxine (LT4). Tablet is the mostly used LT4 formulation, and the fasting regimen is required for the absorption of active principle. Also, gastrointestinal diseases and drugs may impair the LT4 bioavailability when tablet is used. Nonsolid LT4 formulations (i.e., liquid solution (LS) and soft gel (SG) capsule) were manufactured to overcome the limitations of LT4 tablet. This study was conceived to evaluate the performance of nonsolid LT4 formulations in a real-life scenario. Methods. Two institutions participated in the study that was conducted in two phases (i.e., enrollment and re-evaluation). Adults with autoimmune or postsurgical hypothyroidism and on LT4 from a few months were selected. A nonparametric statistical analysis for paired or unpaired data was performed. Results. 121 consecutive cases were included. At the enrollment phase, a 52% of patients took the therapy at least 30 min before breakfast with no difference between tablet and SG/LS users. TSH was 1.65 mIU/L (0.86–2.70) in patients on LT4 tablet and 1.70 mIU/L (1.10–2.17) in those on SG/LS (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.22) and significantly reduced in SG/LS group (p=0.004); among the patients using incorrect LT4 assumption, TSH was significantly increased in those on tablet (p=0.0029) and stable in those on SG/LS (p=0.36). Conclusion. The performance of nonsolid LT4 formulations is not influenced by correct or incorrect use of therapy. On the contrary, LT4 tablet does not guarantee euthyroidism when it is ingested without waiting for at least 30 minutes before breakfast. These new data, obtained in a real-life scenario, suggest that LT4 SG/LS should be regarded as first-line therapy for treating adults with newly diagnosed hypothyroidism.

Levothyroxine Sodium Pentahydrate Tablets – Formulation Considerations

“…There have been fewer malabsorption issues with these alternate dosage forms. 177,179,[257][258][259][260][261][262][263][264][265][266][267] Since these are solution dosage forms, they are suited for patients with reduced gastric acidity due to a variety of reasons -H. pylori infection, concomitant use of proton pump inhibitors or other gastro-intestinal disorders. [268][269][270] Liquid formulations are easier to administer to newborns and drug absorption is faster than from tablets.…”

Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society

“…The aforementioned, together with the fact that quality of life is reported as still impaired, and may not be fully restored despite treatment with LT4 [ 8 ], is one among many factors leading to the pursuit of better treatment options for hypothyroid individuals. The evidence suggests differences in bioavailability in favor of liquid solution and soft-gel capsules compared to tablets both in patients with and without impaired absorption [ 2 , 9 , 10 ]. Soft-gel capsules and liquid solution are more expensive than tablets, and the cost-effectiveness of switching from tablets to these new formulations remains unsettled [ 11 ].…”

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

“…The use of L-T 4 liquid formulation without ethanol concomitantly with breakfast, however, remains off-label. This observation is of remarkable clinical relevance since suboptimal adherence to L-T 4 therapy is more likely to cause TSH variation over time [ 34 , 35 ]. Patients undergoing treatment with L-T 4 are usually asked to ingest the drug in the morning, at least 30 min before having breakfast, because a significantly decreased L-T 4 absorption was reported with food when patients are treated with the usual tablet [ 36 , 37 ].…”