Switching Levothyroxine From the Tablet to the Oral Solution Formulation Corrects the Impaired Absorption of Levothyroxine Induced by Proton-Pump Inhibitors

Vita, Roberto; Saraceno, Giovanna; Trimarchi, Francesco; Benvenga, Salvatore

doi:10.1210/jc.2014-2684

Cited by 89 publications

(68 citation statements)

References 27 publications

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“…These novel formulations display similar pharmacokinetic properties compared to LT4 tablets [17], and are resistant to gastric pH variations and are characterized by higher bioavailability [18][19][20]. 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].…”

Section: Introductionmentioning

confidence: 60%

“…The few previous observational studies investigating the effects of DDI during LT4 therapy in real-life setting were mainly limited to local [33] and small groups of patients [22,[34][35][36][37], or did not specifically investigate the DDIs effects on variations of TSH levels [49] and LT4 prescribed dosages [50].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, those studies were mostly limited to case series [33] or small groups of patients [22,34] in specific settings and/or medical conditions [35] or healthy volunteers [36,37], thus not adequately representing the general population.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Introductionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…These ones showed, as compared to the classic tablet formulation, a similar or better bioavailability as well as a lower number of excipients (45, 46). In clinical studies, softgel or liquid formulations performed better in patients with gastric disorders (47, 48) and in proton pump inhibitors users (49, 50). …”

Section: Clinical Aspects Of Thyrogastric Syndromementioning

confidence: 99%

Hashimoto’s Thyroiditis and Autoimmune Gastritis

Cellini¹,

Santaguida²,

Virili³

et al. 2017

Front. Endocrinol.

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The term “thyrogastric syndrome” defines the association between autoimmune thyroid disease and chronic autoimmune gastritis (CAG), and it was first described in the early 1960s. More recently, this association has been included in polyglandular autoimmune syndrome type IIIb, in which autoimmune thyroiditis represents the pivotal disorder. Hashimoto’s thyroiditis (HT) is the most frequent autoimmune disease, and it has been reported to be associated with gastric disorders in 10–40% of patients while about 40% of patients with autoimmune gastritis also present HT. Some intriguing similarities have been described about the pathogenic mechanism of these two disorders, involving a complex interaction among genetic, embryological, immunologic, and environmental factors. CAG is characterized by a partial or total disappearance of parietal cells implying the impairment of both hydrochloric acid and intrinsic factor production. The clinical outcome of this gastric damage is the occurrence of a hypochlorhydric-dependent iron-deficient anemia, followed by pernicious anemia concomitant with the progression to a severe gastric atrophy. Malabsorption of levothyroxine may occur as well. We have briefly summarized in this minireview the most recent achievements on this peculiar association of diseases that, in the last years, have been increasingly diagnosed.

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“…[6] Der Artikel von Mondal und Mugesh [4] stellt einen großen Fortschritt dar, da er ¾rzten und Patienten eine rationale Grundlage für die Suche nach einer optimalen T4-Therapie liefert. Diese Arbeit setzt Thyroxin auf die Liste der pharmazeutisch aktiven Inhaltsstoffe mit unterschiedlichen Kristallformen.…”

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Schilddrüsenhormone – von der Kristallstruktur über die Aktivität zur Reaktivität

Schweizer

Steegborn

2015

Angewandte Chemie

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Bereits geringe Abweichungen der individuellen Schilddrü-senhor monwerte wirken sich negativ auf das kçrperliche Wohlbefinden aus.E ine T4-Ersatztherapie ist für Tausende Patienten notwendig, denen jedes Jahr die Schilddrüse entfernt wird, sowie für Millionen hypothyreote Patienten, die T4 zur TSH-Suppression bençtigen. l-T4 wird in Tablettenform verabreicht. Dabei wird stillschweigend angenommen, dass das schlecht wasserlçsliche Molekül irgendwie aus der Tablette freigesetzt und während der Darmpassage aufgenommen wird. ¾rzte wissen, dass ihre Patienten mit Nachdruck an einem einmal verordneten T4-Präparat festhalten. Obwohl man sich nicht erklären kann, weshalb 100 mgv on synthetisch reinem Thyroxin der einen Marke nicht mit 100 mgreinem Thyroxin einer anderen Marke äquivalent sein sollten, berücksichtigen gegenwärtige Richtlinien den Wunsch der Patienten. [3] Der kürzlich erschienene Artikel von Mondal und Mugesh über molekulare Eigenschaften des Thyroxins liefert eine erstaunlich einfache Antwort auf dieses Mysterium. [4] Die Autoren kristallisierten synthetisches Thyroxin aus verschiedenen Lçsungsmitteln und fanden zweierlei Kristallformen:e ine trikline (Form I) und eine monokline (Form II). Beide Polymorphe enthielten jeweils zwei Moleküle T4 in der asymmetrischen Einheit, die zudem in verschiedenen Konformationen vorlagen und unterschiedliche intra-und intermolekulare Wechselwirkungen im Kristallgitter eingingen. Die Unterschiede betrafen insbesondere die Orientierung der Amino-und Carboxygruppen zum Diphenyletherrest sowie Abbildung 1. Strukturen und Nummerierung des ProhormonsThyroxin und seines aktiveren Metaboliten T3. Die Affinität des nukleären T3-Rezeptors zu T3 ist mehr als zehnmal hçher als die zu T4. Der Tyrosylring, der die 3-und 5-Iodatome trägt, wird oft als "innerer Ring" bezeichnet, während der Phenolring "äußerer Ring" genannt wird.

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Switching Levothyroxine From the Tablet to the Oral Solution Formulation Corrects the Impaired Absorption of Levothyroxine Induced by Proton-Pump Inhibitors

Abstract: These data demonstrate the continued absorption of liquid LT4 despite the increased gastric pH due to PPI therapy.

Cited by 89 publications

References 27 publications

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

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

Hashimoto’s Thyroiditis and Autoimmune Gastritis

Schilddrüsenhormone – von der Kristallstruktur über die Aktivität zur Reaktivität

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