OTCs: It’s Not Just What, It’s When. Timing is Everything.

February 9, 2015

Levothyroxine (Synthroid, Levoxyl and generics) is the most commonly prescribed drug in the US. Osteoporosis is a common co-morbid condition with hypothyroidism among older females, who also often exhibit iron-deficiency anemia as well.  So what happens in the real world when patients are also medicating with calcium and iron supplements?

A 2015 Clinical Endocrinology study looks to shed some light on this subject.  Authors studied over 10,000 Tayside, Scotland residents (82% female) who were prescribed levothyroxine for hypothyroidism, and found that both calcium and iron supplements were associated with greater TSH levels (indicating less effective treatment). Unfortunately the researchers were not able to capture when levothyroxine and other agents were taken.

Patients taking levothyroxine are typically advised to take a calcium supplement to counter the effects of a low TSH on bone resorption. The American Thyroid Association (www.thyroid.org) and levothyroxine prescribing information have long advised that levothyroxine be taken on an empty stomach and separated from calcium, iron and other mineral supplements (including antacids) by 4 hours.

So what are patients actually doing? Our prior research found that the majority of patients (80%) reported taking calcium within 4 hours, 67% within 1 hour. This practice can reduce levothyroxine absorption by nearly a third.

Trying to educate patients to correctly separate their levothyroxine from potentially risky OTC medications can be a challenge in itself. First of all you have to know exactly WHEN patients are taking each of their medications to see if there is indeed a problem.  Secondly, Individuals who have consistently timed their levothyroxine and calcium supplement may have had their levothyroxine doses increased to maintain therapeutic levels. However, sporadic or inconsistent timing of calcium administration could result in variations in TSH and T4 levels and concomitant symptoms of hypothyroidism. And lastly, patients who have had their levothyroxine dose increased as a result of taking calcium within 4 hours of their levothyroxine could experience an over-suppressed TSH – and even symptoms of hyperthyroidism – if they revise their self-medication regimen upon learning that they should separate their calcium and levothyroxine by 4 hours.

So we really need to know…What, then When, and then What to Do.  Our ActualMeds structured patient interview queries when each medication or supplement is taken and our proprietary rules algorithm tailors alerts around timing. ActualMeds provides a visual heuristic of the self-medication regime – and avoids the over-alerting (“alert fatigue”) seen with other solutions (e.g. a levothyroxine and calcium supplement drug interaction alert regardless of timing). There is no point in firing an alert if the patient is taking levothyroxine and calcium 4 hours apart! If there is a timing issue, ActualMeds prompts clinicians to intervene, patients are educated around proper administration and follow up TSH levels would certainly be recommended. Let’s start asking “When?” after we ask “What?”! It’s all about the timing!

Irving SA, Vadiveloo T, Leese GP. Drugs that interact with levothyroxine. An observational study from the thyroid epidemiology, audit and research study. Clin Endocrinol. 2015;82(1):136-141 http://www.medscape.com/viewarticle/837370?nlid=75075_764&src=wnl_edit_medp_imed&spon=18

Michel R, Neafsey P, Dzurec LC. Self-medication practices among patients taking levothyroxine. Internet J Adv Nurs Pract. 2003;6(2) https://ispub.com/IJANP/6/2/11898

Neafsey P J. Levothyroxine and calcium interaction. Timing is everything. Home Healthcare Nurse. 2004;22(5):338-339.


Patricia J Neafsey, PhD (pharmacology): Co-founder and Principal Scientist, ActualMeds Corporation.  Professor Emeritus, University of Connecticut School of Nursing. @PharmacoQueen

On February 10th, 2015, posted in: OTCs, Self Medication by

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