Tirosint Label Updates 2020-2026: FDA Regulatory Changes for Levothyroxine Gel Caps

What does the FDA record show for 2020 to 2026?

Tirosint capsules were approved on October 13, 2006 as a new dosage form under NDA 021924, standard review [1]. The Drugs@FDA supplement list for that application runs from a 2007 labeling supplement to Supplement 21, action date June 22, 2022, classified as Manufacturing (CMC) - New Strength, with a label posted [1]. That 2022 entry is the only supplement listed inside the 2020-2026 window [1]. The application lists 15 capsule strengths, from 0.013 mg to 0.2 mg [1].

The oral solution is a separate application, NDA 206977, approved December 15, 2016 [3].

What does the levothyroxine boxed warning say?

Levothyroxine labels, including Tirosint, carry a weight-loss warning: thyroid hormones should not be used for the treatment of obesity or for weight loss, doses within the range of daily hormonal requirements are ineffective for weight reduction in euthyroid patients, and larger doses may produce serious or even life-threatening toxicity, particularly with sympathomimetic amines [2]. Tablet labels such as Synthroid cover adult and pediatric patients including neonates. Tirosint capsules are labeled for adults and children 6 years and older who can swallow an intact capsule.

What does the tablet label say about cardiac risk and starting doses?

The tablet label gives a full replacement dose of 1.6 mcg/kg/day for adults with hypothyroidism, titrated in 12.5 to 25 mcg steps every 4 to 6 weeks [2]. Adults at risk of atrial fibrillation or with underlying cardiac disease start below 1.6 mcg/kg/day and are titrated every 6 to 8 weeks [2]. Section 5.2 states that over-treatment may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients [2]. The label also says levothyroxine has a narrow therapeutic index and that overtreatment or undertreatment may have negative effects [2].

What interactions does the tablet label list?

The label addresses calcium and iron, bile acid sequestrants, orlistat, acid-reducing medicines and oral anticoagulants [2].

• Phosphate binders, including calcium carbonate, ferrous sulfate, sevelamer and lanthanum: give levothyroxine at least 4 hours apart from these agents [2].
• Bile acid sequestrants and ion exchange resins: give levothyroxine at least 4 hours before them, or monitor TSH [2].
• Orlistat: monitor for changes in thyroid function [2].
• Proton pump inhibitors, sucralfate and antacids: the label says gastric acidity is essential for adequate absorption, that these may reduce it, and to monitor appropriately; it gives no fixed hour spacing [2].
• Oral anticoagulants: levothyroxine increases the response, a lower anticoagulant dose may be warranted, and coagulation tests should be closely monitored [2].

What does the tablet label say about pregnancy and lactation?

The label says levothyroxine should not be discontinued during pregnancy, and that TSH should be monitored and the dose adjusted during pregnancy [2]. It says levothyroxine is present in human milk and that adequate treatment during lactation may normalize milk production in mothers with low milk supply [2].