TABLET LEVOTHYROXINE (L-T4) MALABSORPTION INDUCED BY PROTON PUMP INHIBITOR: A PROBLEM THAT WAS SOLVED BY SWITCHING TO L-T4 IN SOFT GEL CAPSULE

Objective: To report a patient in whom the impaired absorption of tablet levothyroxine (L-T4) due to a proton pump inhibitor (PPI) use was corrected by switching the patient to the soft gel capsule. Methods: A woman with Hashimoto's thyroiditis-associated hypothyroidism (serum thyroid-stimulating hormone [TSH] 6.8-9.6 mU/L) had been treated with tablet L-T4 (100 mu g/day). Because she used to take pantoprazole just before L-T4 in the morning, TSH failed to normalize (4.4-6.5 mU/L). Thus, the daily dose had been progressively increased to 125 and 150 mu g/day, with serum TSH levels of 2.4 and 0.6 mU/L, respectively. Results: While maintaining pantoprazole, we switched the tablet L-T4 (150 g/day) to a soft gel capsule (125 mu g/day; Tirosint (R) capsule, IBSA, Lugano, Switzerland) and after 2 months, to 100 mu g/day. Serum TSH was lower than under the equivalent regimens with the tablet: 0.5 versus 2.4 mU/L (125 mu g/day) and 2.4 versus 4.4 to 6.5 mU/L (100 mu g/day). Upon switching back to the tablet (100 mu g/day), serum TSH increased to 3.2 and 4.7 mU/L and then dropped to 2.7-3.0 mU/L when the dose was increased to 125 mu g/day. We also acutely evaluated the intestinal absorption of L-T4 by administering 600 mu g LT4 as a tablet or soft gel capsule while maintaining pantoprazole. Pharmacokinetic indices showed better and faster absorption for the soft gel capsule versus tablet (area under the curve [AUC](0-4h) = 16,240 vs. 10,960 nmol/L x 4 hours, maximum absorption [C-max] = 108 vs. 73 nmol/L, and time of maximum absorption [T-max] = 120 minutes vs. 180 minutes). Conclusion: Confirming in vitro studies conducted by other authors, the soft gel capsule L-T4 is negligibly affected by changes in gastric pH compared to tablet L-T4.