Treatment pattern and frequency of serum TSH measurement in users of different levothyroxine formulations: a population-based study during the years 2009–2015 (original) (raw)
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Frontiers in endocrinology, 2018
In the last years, levothyroxine (LT4) has been commercialized also in liquid formulation, which is less sensitive to the factors known to reduce the absorption of tablet LT4. To date, there is no robust information that liquid LT4 can improve pharmacologic thyroid homeostasis of patients with reduced efficacy of tablet LT4. This analysis aimed at achieving solid evidence that switching thyroxine treatment from tablet to liquid preparation improves patients' TSH levels. The search was performed in PubMed/MEDLINE and Scopus database based on the terms "thyroid," "levothyroxine," and "liquid," and updated until September 25, 2017. Studies were included only if they described patients with suboptimal TSH on tablet LT4, subsequently switched to liquid LT4. The literature search retrieved 462 articles and six were finally included. The pooled mean difference of TSH value between tablet and liquid LT4 was 4.23 mIU/L (95% CI from 3.69 to 4.77). Mild hetero...
European Thyroid Journal, 2020
Background: A new liquid levothyroxine (LT4) dissolved in glycerol and water has recently been developed by a Greek pharmaceutical company (Uni-Pharma, Athens, Greece). Objectives: To evaluate the therapeutic equivalence of this new liquid LT4 preparation versus the already existing tablet formulation of the same manufacturer, in order to obtain approval by the Greek National Organization for Medicines. Methods: This was a prospective, randomized, cross-over phase III study. The study included 50 patients (9 men and 41 non-pregnant women, with a mean age of 42.5 ± 12.5 years), with documented overt primary hypothyroidism. All subjects were well controlled on substitution therapy with various LT4 formulations. None of the patients had known LT4 malabsorption. The patients were randomized into 2 groups (A and B). The individuals of group A initially received T4 ® tablets for 10 ± 2 weeks and subsequently switched to T4 ® drops (100 μg/mL solution) at the same dose for another 10 ± 2 weeks. In group B, the reverse procedure was followed. Total T3 (T3), free T4 (fT4), and TSH were measured in all participants at enrollment and at the end of each 10 ± 2-week trial period. Results: Out of the 50 recruited patients, 6 were lost to follow-up and 5 were excluded due to noncompliance with the study protocol. In the 39 patients who completed the study, the serum TSH levels after 10 ± 2 weeks of treatment either with T4 ® tablets or with T4 ® drops did not differ (1.759 ± 1.104 vs. 2.076 ± 1.334 mIU/L, mean ± SD). Conclusions: In hypothyroid patients, the new liquid LT4 preparation (T4 ® drops) is therapeutically equivalent to the tablet form (T4 ® tablets).
European Journal of Drug Metabolism and Pharmacokinetics, 2006
Probably for genetic reasons a substantial part of the Greek population requires Levothyroxine treatment. Since commercially available Levothyroxine was first marketed, the manufacture and storage of the drug in tablet form has been complicated and difficult; and as cases of therapeutic failure have frequently been reported following treatment with this medicinal agent, quality control is an essential factor. Due to the unreliability of Levothyroxine-based commercial products, in the present study we decided to follow the Food and Drug Administration (FDA) guidelines', and use a Levothyroxine solution as reference product. The bioavailability of the Levothyroxine sodium tablet formulation THYROHORMONE@ /Ni-The Ltd (0.2 mg/tab) and that of a reference oral solution (0.3 mg/IOO ml) under fasting conditions were compared in an open, randomized, single-dose two-way crossover study. Twenty four healthy Caucasian volunteers (M/F=IS/9, mean age=32.9±7.4yr) participated in the study. Bioavailability was assessed by pharmacokinetic parameters such as the area under plasma concentration-time curve from time zero up to the measurable last time point (AUC;ast) and the maximum plasma concentration (Cmw). Heparinized venous blood samples were collected pre-dose and up to a 48-hour period post-dose. Levothyroxine sodium in plasma samples was assayed by a validated electrochemiluninescent immunoassay technique. Statistical analysis showed that the post-dose thyrotropin-stimulating hormone (TSH) levels decreased significantly (p<O.OS). Regarding Levothyroxine (T4), the point estimate of the test formulation to the reference formulation ratios (T/R) for AUC;ast and C max was 0.92 with 90% confidence limits (0.90, 0.94) and 0.93 with 90% confidence limits (0.91, 0.94), respectively. Regarding triiodo-L-thyronine (n), the point estimate for the T/R ratios of AUC;ast and C max was 0.92 with 90% confidence limits (0.90, 0.95) and 0.94 with 90% confidence limits (0.92, 0.95), respectively. The 90% confidence limits for the pharmacokinetic parameters AUC;ast and C max lie within the acceptance limits for bioequivalence (0.80, 1.25), for both nand T4.
Drugs in R&D
Introduction Medication changes involving levothyroxine-either dose titrations or switching formulations-occur frequently in patients with erratic thyroid-stimulating hormone (TSH) levels and persistent hypothyroid symptoms. We investigated whether switching patients from levothyroxine tablets to a gel cap formulation of levothyroxine might reduce dose adjustments and improve tolerability and efficacy outcomes. Objectives Primary study objectives included quantifying the percentage of patients achieving TSH levels within a pre-specified range, median dose changes experienced, and the percentage of patients with improved hypothyroid symptom control after switching from levothyroxine tablets to levothyroxine gel caps. Methods A retrospective medical chart review was conducted among 99 randomly selected hypothyroid patients who were switched from a tablet to a gel cap formulation of levothyroxine. Patients were required to have been on levothyroxine monotherapy for C1 year prior to the medication switch. Data was collected for 6 months pre-switch and up to 6 months post-switch. Results Of the 99 patients studied, the majority (51.5%) experienced no documented change in TSH status after the switch (P \ 0.0001). However, there was a decrease in the mean number of dose changes experienced (1.61 ± 0.96 vs. 0.73 ± 0.96; P \ 0.0001). Improved hypothyroid symptom control was reported among 61.6% of patients (61 of 99; P \ 0.0001). Conclusion The results of CONTROL Switch support a strategy of switching patients who may experience tolerability or efficacy problems with standard levothyroxine tablets to the levothyroxine gel cap formulation. Key Points Changes in levothyroxine doses or formulations are common and can increase the use of healthcare resources and lead to poor clinical outcomes. Levothyroxine gel caps are a unique formulation that has been proven to be consistently absorbed in the presence of factors that limit the absorption of levothyroxine tablets. When patients were switched from levothyroxine tablets to gel caps, the majority experienced no improvement in TSH status but significant reductions in dose changes and significant improvement in hypothyroid symptom control. The results of the study were consistent regardless of the reason for medication switch (efficacy or adverse effects) or prior therapy (branded or generic levothyroxine tablets).
Endocrine, 2017
Purpose Several medications may interact with levothyroxine (LT4) intestinal absorption or metabolism, thus reducing its bioavailability. We investigated the variability of thyroid stimulating hormone (TSH) levels and prescribed daily dosages (PDDs) of LT4 before and during potential drug-drug interactions (DDIs) in users of tablets vs. oral liquid LT4 formulations. Methods By using the Italian general practice Health Search Database (HSD), we retrospectively selected adult patients with at least one LT4 prescription from 2012 to 2015 and at least 1 year of clinical history recorded. The incident prescription of interacting medications (e.g., proton pump inhibitors, calcium or iron salts) was the index date. Analysis was carried out using a self-controlled study design. Results Overall, 3965 users of LT4 formed the study cohort (84.1% women, mean age 56 ± 16.5 years). TSH variability on the entry date was greater among liquid LT4 users than in those prescribed with tablets as shown by the difference between 75th and 25th centile, which were 3.01 and 3.8, respectively. The incidence rate ratio (IRR) for TSH variability did not differ between groups, before and during exposure to DDIs. In contrast, PDDs less likely increased during the exposure to DDI with oral liquid LT4 compared with tablets (IRR = 0.84; 95% CI: 0.77-0.92), especially in patients with post-surgical hypothyroidism (IRR = 0.75; 95% CI: 0.64-0.85). Conclusions In clinical practice, the use of oral liquid LT4 is not associated with increased PDDs, compared with tablets formulation, during exposure to DDIs. These results support the need for individualizing LT4 formulation to prescribe, especially in patients with various comorbidities and complex therapeutic regimens.
Biomedical Research-tokyo, 2017
Objectives: The aim of the present study was to investigate the misuse of levothyroxine treatment in patients with hypothyroidism. Methods: Patients who received levothyroxine treatment were included in the study. Age, gender, duration of medication use, Thyrotropin (TSH) level, regular use of medication, time and manner of taking medication, drug storage conditions and use of additional medication were recorded. Taking the medication on a full stomach or in the evening, occasional use of medication, storing the medicine in the refrigerator, and the use of additional medication were classified as misuse of levothyroxine treatment. According to the levels of TSH: 0.4-4.5 mIU/L was considered a normal dose, while 4.5 mIU/L and above was considered insufficient, and 0.4 mIU/L and below was considered as high dose. Results: Patients who received levothyroxine pill were included in the study (average age: 53 ± 14 years, average duration of medication use: 48 ± 50 months and females/male ...
Frontiers in Endocrinology, 2021
Approximately, 5% of the population is affected by hypothyroidism, mainly women and persons aged more than 60 years. After the diagnosis of hypothyroidism the usual therapy is tablet levothyroxine (L-T4), with a monitoring of the thyroid-stimulating hormone (TSH) level in primary hypothyroidism every 6–8 weeks and L-T4 is adjusted as necessary to reach an euthyroid state. Once TSH is stabilized in the normal range, it is recommended to conduct annual testing in the treated subjects to warrant suitable replacement. More recently advances regarding L-T4 treatment are the introduction of new oral formulations: the liquid solution, and soft gel capsule. The soft gel capsule permits a quick dissolution in the acid gastric pH. The liquid preparation does not require an acid gastric environment. Many pharmacokinetic studies demonstrated a more rapid absorption for the liquid L-T4, or capsule, than with tablet. Many studies have shown that the liquid, or capsule, formulations can overcome t...