Tablet Levothyroxine (L-T4) Malabsorption Induced by Proton Pump Inhibitor; A Problem that was Solved by Switching to L-T4 in Soft Gel Capsule

Vita, Roberto; Benvenga, Salvatore

doi:10.4158/ep13316.cr

Cited by 55 publications

(50 citation statements)

References 13 publications

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“…These conditions may be transitory during the life of the patient and may therefore lead to fluctuations of TSH and to transitory undertreatment. 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).…”

Section: Discussionmentioning

confidence: 99%

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

Yue¹,

Benvenga

Scarsi

et al. 2015

J Pharm Pharm Sci

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-Purpose:Clinical studies have suggested that proton pump inhibitors may decrease levothyroxine absorption and an in vitro study suggested that the effect of pH on dissolution may differ with formulation. To determine the impact of formulation on the pharmacokinetics of levothyroxine in altered gastric pH conditions, this study compared the pharmacokinetics of levothyroxine capsules and tablets, two formulations deemed bioequivalent in healthy volunteers under fasting conditions, when taken with or without esomeprazole. Methods: Two clinical studies were conducted in healthy volunteers given single dose levothyroxine (600 g) with a 45-day washout period. In Study 1 (parallel-design/two-way crossover), 16 subjects received either levothyroxine capsules or tablets, each group with or without prior administration of intravenous esomeprazole (maximum dose of 80 mg). In Study 2 (two-way crossover), 16 subjects received both capsules or tablets after intravenous esomeprazole. Blood samples were collected pre-dose and up to 24 hours post-dose. Baselineadjusted pharmacokinetic parameters were calculated: C max (maximal concentration), T max (time to C max ), AUC 0-t (area under the concentration-time curve from 0 to the last detectable concentration), AUC 0-6 and AUC 0-12 (areas under the curve from 0 to 6 and 12 hours, respectively). Analyses of variance were conducted to compare lntransformed C max and AUC. Non-parametric T max analyses were done. Results: In Study 1, esomeprazole caused a greater decrease in overall levothyroxine exposure of tablets vs. capsules (13% vs 6% for C max , 18% vs. 14% for AUC 0-6 , 17% vs. 5% for AUC 0-12 and 10% vs. 8% for AUC 0-t ). In Study 2 esomeprazole administration resulted in a 16% smaller levothyroxine exposure with tablets vs. capsules. No statistically significant differences in T max were found. Conclusions: Although both formulations are considered "bioequivalent" in healthy volunteers, they may not necessarily be bioequivalent in patients with impaired gastric pH conditions. Levothyroxine capsules may therefore be more appropriate for patients with decreased gastric acidity.

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Section: Discussionmentioning

confidence: 99%

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

Yue¹,

Benvenga

Scarsi

et al. 2015

J Pharm Pharm Sci

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“…In addition, we did not consider levothyroxine formulation in this study. Levothyroxine in soft gel capsule formulation was found to result in a higher bioavailability compared to levothyroxine in tablet form when a PPI was co-administered [34]. This suggests the possibility that a switch in the formulation may result in a lower number of levothyroxine prescriptions during the potential DDI, introducing an element of confounding.…”

Section: Discussionmentioning

confidence: 99%

Drug Interactions with Levothyroxine Therapy in Patients with Hypothyroidism: Observational Study in General Practice

et al. 2015

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“…This soft gel capsule contains LT4 in glycerin with a soft gelatin protective shell. A case report described improved absorption compared to LT4 tablet in a person with concurrent proton pump inhibitor use (14). This formulation is listed pregnancy category A (15).…”

Section: Discussionmentioning

confidence: 99%

Levothyroxine Malabsorption Induced by Diabetic Gastroparesis Exacerbated During Pregnancies: Effect of Intramuscular Levothyroxine Injections and Levothyroxine Soft Gel Capsules

Kim

Sachmechi

2015

AACE Clinical Case Reports

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Objective: We report a case of severe hypothyroidism with levothyroxine (LT4) malabsorption induced by diabetic gastroparesis. This was exacerbated during the patient's 2 pregnancies. Management was improved by intramuscular (IM) LT4) injections and LT4 soft gel capsules.Methods: Case report with literature review. Results:A 23-year-old Hispanic female with type 1 diabetes (DM) and hypothyroidism developed diabetic gastroparesis with unpredictable responses to LT4. She had 2 pregnancies during which her oral LT4 was switched to weekly IM injections of LT4 that maintained her euthyroid state. An LT4 absorption test with 1,000 mcg LT4 revealed reduced LT4 absorption. A gastric emptying scan showed delayed emptying, and endoscopy demonstrated a large amount of residual food in the patient's stomach after an overnight fast. Weekly IM injections of LT4 and LT4 soft gel capsules maintained her euthyroid state after her last pregnancy with a follow-up longer than 1-year. A repeat LT4 absorption test with a 1,000-mcg LT4 soft gel capsule preparation demonstrated improved absorption compared to the initial LT4 absorption test. Conclusion:This may be the first patient described in the literature in whom diabetic gastroparesis was associated with impaired oral LT4 absorption and exacerbation during pregnancies. Our experience with this patient suggests that rational management of this problem may include IM LT4 injections or oral LT4 soft gel capsule administration. (AACE Clinical Case Rep. 2015;1:e73-e78) Abbreviations: CHF = congestive heart failure; DM = diabetes mellitus; IM = intramuscular; LT4 = levothyroxine; T4 = thyroxine; TFTs = thyroid function tests; TSH = thyroid-stimulating hormone

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Tablet Levothyroxine (L-T4) Malabsorption Induced by Proton Pump Inhibitor; A Problem that was Solved by Switching to L-T4 in Soft Gel Capsule

Cited by 55 publications

References 13 publications

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

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

Drug Interactions with Levothyroxine Therapy in Patients with Hypothyroidism: Observational Study in General Practice

Levothyroxine Malabsorption Induced by Diabetic Gastroparesis Exacerbated During Pregnancies: Effect of Intramuscular Levothyroxine Injections and Levothyroxine Soft Gel Capsules

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