Drs. Horn and Hansten are both professors of pharmacy at the University of Washington School of Pharmacy. For an electronic version of this article, including references if any, visit www.hanstenandhorn.com.
Levothyroxine is widely used to treat patients with thyroid disorders. Unfortunately, the bioavailability of levothyroxine can be reduced by a variety of other medications, leading to reduced levothyroxine effect. One would expect that thyroid hormones other than levothyroxine would interact similarly with the drugs described in this article.
Are Some Patients at Greater Risk?
Patients with little or no endogenous thyroid function are likely to be at greater risk, because they cannot increase endogenous thyroid output in response to the reduced levothyroxine absorption. Some patients taking levothyroxine have partial residual thyroid function, and when their thyroid hormone concentrations fall, they can increase endogenous production of thyroid hormones by releasing thyrotropin. This can compensate somewhat for the inhibition of levothyroxine absorption. Variability in endogenous thyroid function probably accounts for the large variation in the outcome of these interactions.
What Types of Drugs Inhibit Levothyroxine Absorption?
The usual suspects of medications known to be involved in reducing levothyroxine absorption include sucralfate, iron, binding resins, and others.
Avoiding Levothyroxine Interactions
Calcium carbonate is well documented to reduce levothyroxine absorption. Increased thyrotropin concentrations are likely to occur if the calcium carbonate is given chronically with levothyroxine, and in some patients clinical evidence of hypothyroidism may occur. Aluminum hydroxide also appears to inhibit levothyroxine absorption, and limited clinical evidence suggests that magnesium-containing antacids may also interact.
Sucralfate contains a considerable amount of aluminum, and this probably accounts for its ability to reduce levothyroxine absorption. In one study, giving the sucralfate 8 hours after the levothyroxine circumvented the interaction.
Patients on hemodialysis may need treatment with drugs that can bind phosphate in the gut, thus reducing their phosphate load. The phosphate binder sevelamer (Renagel) has been shown to increase thyrotropin concentrations in patients on levothyroxine; hypothyroid symptoms have been reported. Calcium carbonate also can be used as a phosphate binder and it also interacts with levothyroxine, but limited clinical evidence suggests that calcium acetate may not affect levothyroxine absorption.
Evidence from case reports and clinical studies suggests that iron preparations can inhibit levothyroxine absorption and can result in clinical evidence of hypothyroidism. It seems likely that all iron salts would inhibit levothyroxine absorption, although the magnitude may vary among the various preparations.
Cholestyramine is known to bind to a number of drugs, and has been shown to reduce levothyroxine absorption as well. The effect of other binding resins such as colestipol (Colestid), colesevelam (Welchol), and ezetimibe (Zetia) on thyroid absorption is not as well established, but be alert for the possibility.
Other drugs that have been reported to reduce levothyroxine absorption include ciprofloxacin (Cipro), raloxifene (Evista), and caffeine in coffee. More study is needed to establish whether these interactions are likely to be clinically important.
How Can These Interactions Be Avoided?
In general, it is not necessary to discontinue the drug that is reducing levothyroxine absorption (see box above right). The interactions generally can be circumvented by appropriate adjustment of the dosing times of the levothyroxine relative to the binding agents.