Ask The Experts

Levothyroxine: More Leeway In Timing of Administration?

Typically, patients are instructed to take their levothyroxine in the morning for optimal bioavailability. In order to optimize adherence and symptom control, is there any therapeutic disadvantage in advising patients to switch to bedtime administration?


Its affordability, lack of immunogenicity, and a long history of clinical use justify prescribing levothyroxine as the first-line treatment for patients with hypothyroidism. However, strict administration requirements, such as avoidance of any food or other medications for at least
30 minutes, and preferably 1 hour, should be administered on an empty stomach and taken only with water. These instructions to patients for taking levothyroxine may make it difficult for many to achieve compliance with consistency.Add in other medications, hectic mornings, and changes in daily routines, all of which may compromise patients' ability to take their levothyroxine properly.

Given the risks that come with variations in administration, it would be useful for clinicians to prescribe levothyroxine in a manner that will permit patients to avoid fluctuations in thyroid levels and variable control of symptoms.

The norm is early morning administration with scant evidence in support of alternative dosing strategies. In a recent review,2  which evaluated 4 studies, the researchers found that dosing at night improved thyroid levels in 2 of the studies, worsened control in one study, and the last study showed no difference. Patient-reported quality of life did not differ across the studies; however, one of the studies confirmed that patients preferred a bedtime administration.

Taking levothyroxine at bedtime just as effective as morning time.

While these results do not prove that bedtime administration is better, it offers sufficient support to suggest that it may be as good as morning administration. Therefore, bedtime administration can be a viable option for some patients.






Which patients will benefit most from night-time administration?

For patients who are consistent with their morning administration, exhibit thyroid function levels within appropriate ranges, and have no multi-medication challenges that impose the risk of adverse interactions (ie, calcium supplement), there is little need to explore alternative administration strategies to the am norm.

However, for any patient who is struggling with an inconsistent administration and/or is experiencing fluctuating thyroid levels, which will invariably lead to changes in symptom control, these factors present the opportunity for clinicians to suggest an alternative dosing strategy, such as bedtime administration.

While not all patients may be candidates for evening administration, those who indicate the following conditions could try the change to bedtime, at least for a trial:

  • A consistent bedtime routine
  • Does not take other medications in the evening,
  • Has experienced fluctuating thyroid levels and poor symptom control

When the response is affirmative for a consistent routine at bedtime and there are no competing medication needs, the option of switching to the evening is worthy of consideration, particularly for patients who express this desire or for whom better adherence may be enhanced by this recommendation, even for a trial period.

When patients are going to take their levothyroxine at bedtime, the following instructions should be provided:

  • Take levothyroxine as close to 4 hours after the last meal/snack, as possible
  • Institute strategies, such as calendars, alarms, and pill-boxes to aid in compliance (just as they would for morning administration)

Interestingly, it is worth reconsidering the rigidity of the 4-hour post meal rule since there is a study in which levothyroxine was administered 2 hours after the evening meal, and the researchers found no difference in thyroid function studies, quality of life, or dose requirements in comparison to patients taking levothyroxine according to the currently recommended 4-hour window after a meal.  

Scheduling multiple medications to avoid interactions

Ideally, levothyroxine should be the only medication administered at bedtime.  Just as with morning dosing, it is best to avoid coadministration with other medications. Clinicians will, of course, want to keep these suggestions in mind:

  • For patients who also take other medications that require evening administration, consider adjusting the timing of the other medications, such as with the evening meal or at least 2 hours prior to bedtime.
  • When the patient is taking an interacting medication that typically requires 2 or 3 daily doses, consider changing to a once-daily formulation to free up the bedtime for the lone dose of levothyroxine.
  • For a once daily medication that may require bedtime administration, such as sleep aids or some statins, it would be beneficial to design a schedule in collaboration with the patient. For example, with the long-acting statins: rosuvastatin and atorvastatin, although bedtime is often recommended, it is not required and could, therefore, be taken after dinner.

Prior to pursuing bedtime administration patients should be counseled on the administration requirements to determine if evening administration does, in fact, offer an advantage over maintaining morning administration. 

Close monitoring of thyroid levels and patient symptoms will, of course, be needed to assure that the thyroid labs remain within the acceptable reference ranges.

The authors report no conflicts of interest.

Continue Reading
American Thyroid Association Guideline: Treatment of Hypothyroidism Other Than Levothyroxine Monotherapy
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