Helping Patients Take Levothyroxine

Background

Levothyroxine is absorbed extensively in the small bowel when taken orally.1 Its absorption is up to 80%.2-4 However, levothyroxine is considered a narrow therapeutic index drug and a number of drug interactions can result in reduced absorption. Health care professionals are accustomed to instructing patients to take levothyroxine first thing in the morning on an empty stomach to minimize these interactions. However, there may be other options for patients who have trouble sticking with this regimen. This document reviews the various options for administration of oral levothyroxine.

Options for Taking Levothyroxine

The key to getting a consistent effect with levothyroxine therapy is taking the drug regularly and consistently. Help patients figure out a personalized strategy to optimize administration.

Morning administration. The general instruction is to take levothyroxine on an empty stomach before breakfast, other meds, or even coffee. It appears to be absorbed better when taken 60 minutes before a meal compared with 30 minutes before a meal.4 However, giving patients a little leeway by instructing them to take levothyroxine doses 30 to 60 minutes before breakfast or coffee may help improve compliance.2-5

A real problem that clinicians point out is for those who also take a bisphosphonate in the morning. Like levothyroxine, most bisphosphonates must be taken on an empty stomach first thing in the morning. They must generally be taken at least 30 minutes before other meds, food, or drink other than water.6,11 This could result in a complicated regimen: take the bisphosphonate, wait 30 minutes, take levothyroxine, wait 30 to 60 minutes, then have breakfast. (Remember that patients shouldn’t lie down after taking bisphosphonates to avoid esophageal irritation. So there’s no hitting the “snooze” button.)6,11

The purpose of taking a bisphosphonate on an empty stomach and apart from other meds is to optimize absorption of the bisphosphonate. They have poor oral absorption at less than 1%.6,7 However, there is no actual evidence of an interaction between bisphosphonates and levothyroxine.

Options for evening administration. Patients can take levothyroxine at night. This may be best for those who take a bisphosphonate or other interacting drug that requires significant separation from levothyroxine in the morning. These interacting drugs include bile acid sequestrants, calcium supplements, iron supplements, raloxifene, sevelamer, and sucralfate.5

One study showed that taking levothyroxine 60 minutes before breakfast provided better absorption than taking it two hours after the last meal of the day or 20 minutes before breakfast.4 However, another study suggests that levothyroxine is actually better absorbed when it’s taken four hours after the last meal of the day compared to when it’s taken 30 minutes before breakfast.1,4 The reasons for this might be high gastric acidity at night compared to morning, and slower gastric motility at night compared to morning. Both of these could help increase absorption of levothyroxine.1

Other options for those who also take a bisphosphonate. For levothyroxine patients who also take a bisphosphonate, another alternative might be to switch the patient to a weekly (e.g., Actonel, Actonel DS-Canada, Atelvia-U.S., Fosamax), monthly (e.g., Actonel, Boniva-U.S.), or injectable (e.g., Reclast-U.S., Aclasta-Canada) bisphosphonate. Some clinicians try creative solutions such as having patients take levothyroxine just six days a week, and then a weekly bisphosphonate on the day off. Once again, they stress that consistency is key.

The delayed-release risedronate products are to be taken once weekly either with (Actonel DR) or after (Atelvia) breakfast. These formulations are another option for patients who take levothyroxine in the morning.7,10

Product Availability

Levothroid (U.S. only) from Forest Labs has not been available since the summer due to manufacturing problems. The future availability of the product is not known at this time.8 It is on long-term backorder as per the manufacturer.

Patients who have been using Levothroid will require a switch to another product. Be sure to follow the general recommendation for switching formulations of levothyroxine: check TSH about six to eight weeks after starting the new product.4,9 We have generic equivalents for U.S. levothyroxine products in our PL Chart, Generic Substitution for Commonly Prescribed Drugs.

Conclusion

Emphasize adherence and consistency to patients who take levothyroxine. Help them tailor their dosing schedules, and counsel on the importance of taking doses at the same time and under the same conditions each day. Taking levothyroxine on an empty stomach is preferred for the best absorption. Consider recommending 30 to 60 minutes before breakfast or four hours after the last meal in the evening, depending on what works best for the patient.

Project Leader in preparation of this PL Detail-Document: Stacy A. Hester, R.Ph., BCPS, Assistant Editor

References

  1. 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.
  2. Product information for Synthroid. Abbott. North Chicago, IL 60064. June 2011.
  3. eCPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2012. Synthroid monograph and patient information (April 2011). http://www.e-therapeutics.ca. (Accessed October 15, 2012).
  4. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: co-sponsored by American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract 2012;11:1-207.
  5. PL Detail-Document, Drugs and Substances that Reduce Absorption of Levothyroxine. Pharmacist’s Letter/Prescriber’s Letter. December 2008.
  6. Product information for Fosamax. Merck. Whitehouse Station, NJ 08889. June 2012.
  7. Product information for Atelvia. Warner Chilcott. Rockaway, NJ 07866. October 2011.
  8. Forest Laboratories (FRX) drops after cutting 2013 profit forecast. June 11, 2012. http://www.istockanalyst.com/finance/story/5889739/forest-laboratories-frx-drops-after-cutting-2013-profit-forecast. (Accessed October 8, 2012).
  9. Baskin HJ, Cobin RH, Duick DS, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 2002;8:457-69.
  10. Product monograph for Actonel/Actonel DR. Warner Chilcott Canada. Toronto, ON M5W 3N7. July 2011.
  11. eCPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2012. Fosamax monograph (November 2011). http://www.e-therapeutics.ca. (Accessed October 15, 2012).

Cite this document as follows: PL Detail-Document, Helping Patients Take Levothyroxine. Pharmacist’s Letter/Prescriber’s Letter. November 2012.

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