Synthroid Regret, Stopping, and Restarting: What Patients Actually Experience

At a glance

• Drug / levothyroxine sodium (T4); brands include Synthroid, Levoxyl, Tirosint
• Based on / the levothyroxine sodium tablet label, which covers adults and pediatric patients including neonates [1]
• Full replacement dose / 1.6 mcg/kg/day in adults with hypothyroidism [1]
• Dose steps / 12.5 to 25 mcg every 4 to 6 weeks [1]
• Spacing from calcium and iron / at least 4 hours [1]

Which product form does this cover?

The information below is based on the levothyroxine sodium tablet label [1]. Product forms and instructions differ: Tirosint is a soft gelatin capsule and Synthroid is a tablet, and brands and generics are approved under separate applications [2]. This tablet label covers adults and pediatric patients, including neonates [1].

What does the label say about stopping?

The label says to administer the tablets once daily, on an empty stomach, one-half to one hour before breakfast, with a full glass of water [1]. It describes a narrow therapeutic index; overtreatment or undertreatment may affect growth and development, cardiovascular, bone, cognitive, gastrointestinal, and glucose and lipid function [1]. For pregnancy, the label says levothyroxine should not be discontinued, that TSH should be monitored and the dose adjusted, and that the dose should return to the pre-pregnancy dose immediately after delivery [1]. The boxed warning says thyroid hormones should not be used for obesity or weight loss, and larger doses may cause serious or life-threatening toxicity, particularly with sympathomimetic amines [1].

How does the label describe dosing and titration?

For adults diagnosed with hypothyroidism, the label gives a full replacement dose of 1.6 mcg/kg/day, titrated by 12.5 to 25 mcg every 4 to 6 weeks until the patient is euthyroid. Adults at risk for atrial fibrillation or with cardiac disease start lower (less than 1.6 mcg/kg/day) and are titrated every 6 to 8 weeks [1]. The peak effect of a dose may not be reached for 4 to 6 weeks [1]. For patients whose cardiac symptoms develop or worsen, the label describes reducing the dose or withholding it for one week and restarting at a lower dose [1]. The label also says to stop biotin and biotin-containing supplements at least 2 days before TSH and/or T4 levels are assessed [1].

What can reduce levothyroxine absorption?

Calcium, iron, certain gastric-acidity medicines, and other drugs can reduce levothyroxine absorption or change thyroid test results [1]. The label says to give levothyroxine at least 4 hours apart from phosphate binders such as calcium carbonate and ferrous sulfate [1]. In an uncontrolled study of 20 adults, calcium carbonate 1,200 mg/day taken with levothyroxine for 3 months lowered mean free T4 from 17 to 15 pmol/L and raised mean TSH from 1.6 to 2.7 mIU/L [3]. In an uncontrolled study of 14 patients, ferrous sulfate 300 mg taken with thyroxine daily for 12 weeks raised mean TSH from 1.6 to 5.4 mU/L, and 9 had more hypothyroid symptoms [4]. For PPIs, antacids and sucralfate, the label gives no fixed spacing; it says they may reduce absorption and patients should be monitored [1]. In an open-label study of 47 thyroidectomized patients on PPIs, switching from tablets to soft capsules at the same dose was followed by a mean TSH fall of 0.32 mIU/L at 6 weeks and 0.68 mIU/L at 12 weeks (45 completed); there was no control group [5].

Frequently asked questions

›What does the label say about stopping levothyroxine?

The label is written for once-daily dosing and describes risks of undertreatment across growth, cardiovascular, bone, cognitive, gastrointestinal, and metabolic function [1]. It says levothyroxine should not be discontinued during pregnancy, and that TSH should be monitored and the dose adjusted [1].

›How long does a dose take to reach its full effect?

The label says the peak effect of a given dose may not be attained for 4 to 6 weeks [1].

›Can I take levothyroxine with calcium or iron?

The label says to give it at least 4 hours apart from phosphate binders, including calcium carbonate and ferrous sulfate [1]. In one uncontrolled study of 20 adults, calcium taken with levothyroxine raised mean TSH from 1.6 to 2.7 mIU/L [3]; in another of 14 patients, ferrous sulfate taken with thyroxine raised mean TSH from 1.6 to 5.4 mU/L [4].

References

1. U.S. National Library of Medicine, DailyMed. Levothyroxine sodium prescribing information. Levothyroxine sodium label
2. U.S. Food and Drug Administration. U.S. Food and Drug Administration
3. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283(21):2822-5. Effect of calcium carbonate on the absorption of levothyroxine
4. Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117(12):1010-3. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism
5. Sachmechi I, Lucas KJ, Stonesifer LD, Ansley JF, Sack P, Celi FS, et al. Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study. Thyroid. 2023;33(12):1414-1422. Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study