Thyroxine softgel capsule in patients with gastric-related T4 malabsorption

Abstract

The key role of an intact gastric acid secretion for subsequent intestinal T4 absorption is supported by an increased requirement of thyroxine in patients with gastric disorders. A better pH-related dissolution profile has been described in vitro for softgel T4 preparation than for T4 tablets. Our study was aimed at comparing softgel and tablet T4 requirements in patients with gastric disorders. A total of 37 patients with gastric-related T4 malabsorption were enrolled, but only 31 (28F/3M; median age = 50 years; median T4 dose = 2.04 μg/kg/day) completed the study. All patients were in long-lasting treatment (>2 years) with the same dose of T4 tablets when treatment was switched to a lower dose of softgel T4 capsules (-17 %; p = 0.0002). Assessment of serum FT4 and TSH was carried out at baseline and after 3, 6, 12, and 18 months after the treatment switch. In more than 2/3 of patients (good-responders n = 21), despite the reduced dose of T4, median TSH values were similar at each time point (p = 0.3934) with no change in FT4 levels. In the remaining patients (poor-responders n = 10), TSH levels were significantly higher at each time point than at baseline (p < 0.0001). To note, in five of them intestinal comorbidity was subsequently detected. Comorbidity associated with poor-responders status was the only significant predictor in multivariate analysis (OR = 11.333). Doses of softgel T4 capsules lower than T4 tablet preparation are required to maintain the therapeutic goal in 2/3 of patients with impaired gastric acid secretion.

When Bioequivalence in Healthy Volunteers May not Translate to Bioequivalence in Patients: Differential Effects of Increased Gastric pH on the Pharmacokinetics of Levothyroxine Capsules and Tablets

“…In a published case report, a hypothyroid woman who was taking proton pump inhibitors and who failed to be normalized by levothyroxine administered in the form of a tablet was instead normalized when switched to the capsule (17). A recent study conducted in patients with impaired gastric acid secretion, demonstrated that lower doses of levothyroxine were required to maintain the therapeutic goal when administered in the capsule formulation with respect to a tablet (18).…”

Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study

“…All patients with NTMG were treated with an individually tailored dose of T 4 , as previously described (21,22,23,24) and in semi-suppressive mode (target serum TSHZ0.1-0.5 mU/l) (2). The individually tailored dose is the dose of T 4 which is administered following a standardized assumption procedure and titrated on the basis of patient's age, weight, BMI, the amount of residual thyroid tissue and the ability to absorb the hormone (12,14,15,21,22,23,24).…”

“…The individually tailored dose is the dose of T 4 which is administered following a standardized assumption procedure and titrated on the basis of patient's age, weight, BMI, the amount of residual thyroid tissue and the ability to absorb the hormone (12,14,15,21,22,23,24). All patients were treated with the same brand of oral and agreed to take T 4 under fasting conditions, abstaining from eating or drinking anything other than water for at least 1 h after treatment.…”

Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care

“…These findings have been confirmed by recent clinical studies reporting significant reductions of TSH levels [21][22][23][24][25] and measurement frequency (as proxy of clinical efficacy) in patients switching from tablets to oral liquid LT4 formulations [26] in the absence of malabsorption or drug interference. In addition, oral liquid solutions of LT4, not requiring dissolution and speeding up the absorption as compared to tablets [17,18,27], have been demonstrated to circumvent LT4 malabsorption in cases of gastrointestinal diseases [28][29][30] and surgery [31,32].…”