Levothyroxine: best taken at bedtime

New study results suggest that levothyroxine improves thyroid hormone levels more when taken at bedtime compared to taking the drug in the morning on an empty stomach. Levothyroxine is one of the most prescribed medications. About 70–80% of the drug is absorbed orally, with absorption occurring in the small intestine. The current consensus is that levothyroxine is best taken before breakfast to prevent interference of its intestinal uptake by food or other medications.

The study was planned when the authors noticed that thyroid hormone levels improved markedly in several patients after switching from morning to bedtime levothyroxine dosing. The six-month, randomized, double-blind crossover trial was conducted in 105 patients with primary hypothyroidism. Patients were instructed to take one capsule in the morning (1/2 hour before breakfast) and one capsule at bedtime (one capsule contained levothyroxine and the other placebo; most patients ate only a small snack or nothing for several hours prior to bedtime). The capsule administration times were then switched after three months. The placebo and levothyroxine capsules were visually identical and patients received the same dose of levothyroxine as before entry into the trial.

Compared to morning levothyroxine intake, bedtime ingestion resulted in a 1.25 mIU/L reduction in thyrotropin level (p < 0.001), a 0.07 ng/dL increase in free thyroxine level (p = 0.01) and a 6.5 ng/dL increase in total triiodothyronine level (p = 0.02). No significant differences were seen between the two treatment groups in any of the secondary outcome measures (creatinine and lipid levels, body mass index, heart rate and quality of life).

The investigators conclude that clinicians should consider prescribing levothyroxine intake at bedtime as an alternative to morning dosing, provided that the bedtime dose is taken on an empty stomach. Although the higher thyroid hormone levels with bedtime administration did not translate into quality of life benefits, bedtime administration may be more convenient than morning intake since patients do not have to postpone breakfast.

Reference
Bolk N, Visser TJ, Nijman J, et al. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med 2010;170:1996-2003. (accessed January 3, 2010).