Drugs That Inhibit Levothyroxine Absorption

Drs. Horn and Hansten are both professorsof pharmacy at the University ofWashington School of Pharmacy. Foran electronic version of this article,including references if any, visitwww.hanstenandhorn.com.

Levothyroxine is widely used totreat patients with thyroid disorders.Unfortunately, the bioavailabilityof levothyroxine can be reducedby a variety of other medications, leadingto reduced levothyroxine effect. Onewould expect that thyroid hormonesother than levothyroxine would interactsimilarly with the drugs described inthis article.

Are Some Patients at GreaterRisk?

Patients with little or no endogenous thyroidfunction are likely to be at greaterrisk, because they cannot increaseendogenous thyroid output in responseto the reduced levothyroxine absorption.Some patients taking levothyroxinehave partial residual thyroid function,and when their thyroid hormone concentrationsfall, they can increase endogenousproduction of thyroid hormonesby releasing thyrotropin. This can compensatesomewhat for the inhibition oflevothyroxine absorption. Variability inendogenous thyroid function probablyaccounts for the large variation in theoutcome of these interactions.

What Types of Drugs InhibitLevothyroxine Absorption?

The usual suspects of medicationsknown to be involved in reducinglevothyroxine absorption include sucralfate,iron, binding resins, and others.

Avoiding Levothyroxine Interactions

• If possible, do not take the levothyroxine(or other thyroid replacement)within 6 hours of the binding agent. Thegreater the separation the better.
• Try to maintain a constant time intervalbetween taking the levothyroxineand the binding agent. By doing this,any interaction that occurs will tendto be consistent from day to day, andunwanted fluctuations in levothyroxineabsorption will be minimized.
• Any time a binding agent is added ordeleted from the regimen of a persontaking levothyroxine, be alert for clinicalevidence of altered thyroid function.The same is true if either the doseof the binding agent or the intervalbetween doses of the levothyroxineand the binding agent have changed.Measurement of thyrotropin concentrationsmay be needed in some cases.

Antacids

Calcium carbonate is well documentedto reduce levothyroxine absorption.Increased thyrotropin concentrationsare likely to occur if the calcium carbonateis given chronically with levothyroxine,and in some patients clinicalevidence of hypothyroidism may occur.Aluminum hydroxide also appears toinhibit levothyroxine absorption, andlimited clinical evidence suggests thatmagnesium-containing antacids mayalso interact.

Sucralfate

Sucralfate contains a considerableamount of aluminum, and this probablyaccounts for its ability to reduce levothyroxineabsorption. In one study, givingthe sucralfate 8 hours after the levothyroxinecircumvented the interaction.

Phosphate Binders

Patients on hemodialysis may needtreatment with drugs that can bindphosphate in the gut, thus reducing theirphosphate load. The phosphate bindersevelamer (Renagel) has been shown toincrease thyrotropin concentrations inpatients on levothyroxine; hypothyroidsymptoms have been reported. Calciumcarbonate also can be used as a phosphatebinder and it also interacts withlevothyroxine, but limited clinical evidencesuggests that calcium acetate maynot affect levothyroxine absorption.

Iron

Evidence from case reports and clinicalstudies suggests that iron preparationscan inhibit levothyroxine absorptionand can result in clinical evidence ofhypothyroidism. It seems likely that alliron salts would inhibit levothyroxineabsorption, although the magnitude mayvary among the various preparations.

Binding Resins

Cholestyramine is known to bind to anumber of drugs, and has been shownto reduce levothyroxine absorption aswell. The effect of other binding resinssuch as colestipol (Colestid), colesevelam(Welchol), and ezetimibe (Zetia) onthyroid absorption is not as well established,but be alert for the possibility.

Other Drugs

Other drugs that have been reportedto reduce levothyroxine absorptioninclude ciprofloxacin (Cipro), raloxifene(Evista), and caffeine in coffee. Morestudy is needed to establish whetherthese interactions are likely to be clinicallyimportant.

How Can These Interactions BeAvoided?

In general, it is not necessary to discontinuethe drug that is reducing levothyroxineabsorption (see box above right). The interactionsgenerally can be circumvented byappropriate adjustment of the dosingtimes of the levothyroxine relative tothe binding agents.