A Pivotal Field Study to Support the Registration of Levothyroxine Sodium Tablets for Canine Hypothyroidism

Abstract

A prospective, pivotal, multicenter field study to evaluate the dose regimen, effectiveness, and safety of levothyroxine sodium tablets, USP for the treatment of hypothyroidism and hypothyroidism-associated clinical signs in dogs was conducted. Ninety-two dogs diagnosed with primary hypothyroidism met the entrance criteria and were enrolled into the study. Levothyroxine sodium was administered to each dog on a daily basis either as the whole dose q 24 hr or as half the dose q 12 hr. Dosing started at 0.1 mg/10 lb (0.022 mg/kg) and continued for approximately 6 mo to Day 182. During this time, the thyroid status of each dog was evaluated at monthly intervals. For the determination of effectiveness, dogs classified as euthyroid at Day 182, based on their thyroid hormone values, were considered treatment successes. Results of the statistical analysis showed that there was no difference between the two dosing regimens (P = .11) and that when the data from both groups were pooled, the overall success rate was 75.64% (95% confidence interval = 66.34%). By Day 182, improvement and/or resolution of hypothyroidism-associated clinical signs was observed in all categories. No abnormal trends in the reported adverse events were observed.

Clinical Efficacy of Levothyroxine Sodium plus I 131 in the Treatment of Patients with Thyroidectomy and Its Effect on the Levels of Thyroglobulin and Thyrotropin

“…The main component of levothyroxine sodium tablets is levothyroxine sodium [ 13 ] which is currently mostly used in the treatment of non-toxic goiter [ 14 ], post-thyroidectomy suppressive therapy, and adjuvant therapy of hyperthyroidism [ 15 ]. The synthetic levothyroxine it contains is identical to the thyroxine naturally secreted by the thyroid gland and is converted to T3 in peripheral organs, which then exerts its specific effects by binding to T3 receptors [ 16 ].…”

Dog Size and Patterns of Disease History Across the Canine Age Spectrum: Results from the Dog Aging Project

“…Hypothyroidism was more prevalent in larger dogs, and this diagnosis alone was responsible for most of the trend by size for the endocrine category. While untreated hypothyroidism can cause significant morbidity and even mortality, it is relatively easy and inexpensive to treat in dogs (41,42). In contrast, Cushing’s disease and diabetes mellitus, two frequently diagnosed diseases that are more prevalent in smaller dogs in our cohort, carry greater mortality risk and financial burden for the owner (43–46).…”

Safety of orally administered,USP‐compliant levothyroxine sodium tablets in dogs

“…Newly diagnosed patients should have a clinical assessment performed 4–8 weeks after the start of dosing. Clinical resolution of activity level and serum cholesterol concentration is expected in most dogs by that time, with the dermatologic condition showing overt improvement (Lewis et al., ). Serum TT4 concentrations from samples collected 4–6 hr the last dose should be within the therapeutic monitoring range for the reference laboratory used.…”

“…Please note that at the time this study was performed, the recommended starting dose for levothyroxine sodium tablets in dogs was a range of 0.022–0.044 mg kg −1 day −1 , and the top end of this range was chosen to represent a 1× dose. Since then, the companion efficacy study revealed a starting dose of 0.022 mg kg −1 day −1 to be more appropriate for this specific formulation (Lewis et al., ). Each treatment group contained four males and four females.…”

“…The objective was to investigate the safety of levothyroxine sodium, in this specific tablet formulation, given to dogs every 24 hr at dosages of 0, 0.044, 0.132, or 0.220 mg/kg for 182 days. As the recommended starting dosage, which was later established by the companion Efficacy study (Lewis, Morrow, Jacobsen, & Lloyd, ), for this levothyroxine sodium tablet formulation in dogs is 0.022 mg kg −1 day −1 , the 0.044, 0.132, and 0.220 mg/kg dosages represent a 2×, 6×, and 10× overdose, respectively. The hypothesis was that despite the tighter quality standards for Thyro‐Tabs® Canine, because dogs in general handle repeated dosages up to 0.11 mg kg −1 day −1 well, the primary outcome would be suppression of the HPT axis with other effects being clinically not important.…”