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September 3, 2008

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The thyroid medication levothyroxine (LEVO-T, LEVOXYL, NOVOTHYROX, SYNTHROID, THYRO-TABS, UNITHROID) is used to treat hypothyroidism, an endocrine disorder resulting from a thyroid homone deficiency that affects about 4.6 percent of the U.S. population. The medication is used to replace the missing or deficient amount of thyroid hormone. The number of prescriptions for levothyroxine filled each year—more than 75 million U.S. prescriptions in 2007 — makes it one of the mostprescribed drugs in the country.  

Unfortunately, the use of other medications while taking levothyroxine could have one of several kinds of unintended results:  

• Certain medications can decrease the absorption of levothyroxine resulting in lower levels in the blood.

• Other medications can increase the rate at which the body gets rid of levothyroxine, also resulting in lower thyroid levels in the blood.

• Other medications can cause changes of levothyroxine binding in blood

• Levothyroxine can affect the safety or effectiveness of other medications by raising or lowering the levels of these other drugs in the blood.

Drug interactions that reduce absorption of levothyroxine

Some drugs may interact with levothyroxine by thwarting the absorption of this thyroid drug. This effect can be avoided by taking thyroxine considerably before or, in some cases, after the other drug. That allows the levothyroxine to get absorbed without interacting with the second drug.

Antacids often used to treat heartburn and other intestinal distress, including calcium products such as TUMS or ROLAIDS and other antacids, may have absorption-inhibiting effects on thyroid medications. People should take levothyroxine four to six hours before or after taking these antacids.

Iron supplements (FEOSOL, SLOW FE) have been shown to reduce the effect of levothyroxine in some people, although the effect is highly variable from one person to another. Other iron preparations may also have similar effects. Again, we advise taking the levothyroxine four to six hours before or after the iron.

Sucralfate (CARAFATE), used to treat ulcers and other gastrointestinal diseases, appears to inhibit the absorption of levothyroxine. Trials found that this interaction was avoided when the thyroid drug was given eight hours after the sucralfate.

Sevelamer (RENAGEL, RENVELA), which is used to reduce excessive blood phosphate in persons with severe chronic kidney disease, also interferes with the absorption of levothyroxine. Separating the doses of the two types of drugs by at least four to six hours is likely to avert the interaction.

Cholestyramine (Questran) lowers cholesterol by increasing the conversion of cholesterol to bile acids. But it also tends to reduce levothyroxine’s absorption and effect. Similar agents such as colestipol (COLESTID) and cholesevelam (WELCHOL) may have the same effect, although there is not as much evidence for this. We recommend separating all of these medications, known as “bile acid binders,” from the taking of levothyroxine by at least four to six hours.

The antibiotic ciprofloxacin (CIPRO) was associated with reduced levothyroxine effect in case reports, but more information is needed to establish whether the interaction occurs. Until more information is available, it would be prudent to separate doses of ciprofloxacin from those of levothyroxine by at least four hours. The same precaution should apply to other antibiotics in the same class, such as levofloxacin (LEVAQUIN), lomefloxacin (MAXAQUIN), monifloxacin (AVELOX), norfloxacin (NOROX-IN), and ofloxacin (FLOXIN).

Raloxifene (EVISTA), used to treat osteoporosis, may reduce the absorption of levothyroxine, although the evidence to date is not sufficient to establish the extent of the interaction. In one case, separating the two drugs by 12 hours appeared to avert the interaction.

Drugs that increase metabolism of levothyroxine, lowering blood levels

Enzyme inducers stimulate the production of enzymes, which in turn increase levothyroxine from the body. In patients with normal thyroid function, the body compensates for this by producing more thyroid hormone, thus normalizing thyroid levels. But this feedback mechanism is impaired in those taking levothyroxine, and they may not be able to respond appropriately. The result is that they can may become hypothyroid when they take certain enzyme-inducing drugs and may need an increased dose of levothyroxine to make up for the deficiency. Following are several categories of enzyme inducers that can lower blood thyroid levels:  

Antiepileptic drugs used to treat seizures — including carbamazepine (TEGRETOL), oxcarbazepine (TRILEPTAL), phenobarbital (LUMINAL, SOLFOTON), primidone (MYSOLINE), and phenytoin (DILANTIN) — can increase the metabolism of levothyroxine and would require larger doses of the drug.  

Antimicrobial agents used to treat infections also may reduce the effect of levothyroxine. Rifampin (RIFADIN) is a potent enzyme inducer, and is known to have produced hypothyroidism in a patient on levothyroxine therapy. The following antimicrobials are also enzyme inducers and may have a similar effect: efavirenz (SUSTIVA), nevirapine (VIRA- MUNE), rifabutin (MYCOBUTIN) and rifapentine (PRIFTIN).

St. John’s wort is also an enzyme inducer. One study found that it may increase levothyroxine metabolism. Taking the two drugs should be avoided, but if you decide to use the combination, you should tell your doctor and be on the alert for any symptoms of hypothyroidism (e.g., low energy, fatigue, depression, dizziness, weight gain and anemia).

Other drugs that may increase elimination of thyroid hormone include imatinib (GLEEVEC), which is used to treat leukemia and other cancers and may result in hypothyroidism when used together with levothyroxine.

The selective serotonin reuptake inhibitor (SSRI) sertraline (ZOLOFT), widely prescribed for depression, has been associated with a decrease in the effect of levothyroxine. Further studies are needed on this, and on any similar effects of other SSRIs.

Interactions that result in changes of levothyroxine binding in blood

Thyroxine-binding globulin (TBG) is a protein that binds to and carries thyroid hormone in the bloodstream. When the level of TBG is high, levothyroxine is trapped in the bloodstream and cannot get into the tissues where it is needed. If the thyroid is functioning properly, it will compensate for this by producing more thyroid hormones. But if the thyroid is impaired — as is the case for most people taking levothyroxine — an increase in TBG induced by another drug may produce symptoms of hypothyroidism because the thyroid can not produce more hormone.

Estrogens increase TBG, and women who are taking them at the same time they are on levothyroxine may need to increase their dose of the latter. Transdermal estrogen replacement (via patch) does not have much effect on TBG, so this may be preferable for women taking levothyroxine. Oral contraceptives containing estrogens (whether oral or via patch) increase TBG and may increase a woman’s levothyroxine requirements.  

Effects of levothyroxine with warfarin (COUMADIN)

Warfarin (COUMADIN) can interact with levothyroxine, but the results can range from negligible to life-threatening. When a person’s thyroid function is too high, the warfarin’s anticoagulant effects will be magnified and a “normal” dose of warfarin will therefore cause the blood to be too thin and may cause bleeding. Conversely, a person whose thyroid function is too low will not respond normally to the anticoagulant, will be somewhat warfarin-resistant, and the blood will not be thin enough, that is, will clot too easily.

Those who are on stable, appropriate doses of both warfarin and levothyrozine should be all right as long as their thyroid function is stable and the measure of blood thinning, the INR, is in the normal range. But those who are first on warfarin and then later start on levothyroxine run the risk of a magnified effect of warfarin, which can result in dangerous bleeding. In this case, the patient is likely to already be on a large dose of warfarin because the hypothyroidism has rendered them somewhat warfarin-resistant. When the hypothyroidism is corrected by the levothyroxine the warfarin response returns to normal and the blood becomes too thin; life threatening bleeding has occurred from this series of events.

In order to avoid such harmful interactions, patients need to know that their thyroid status can affect their warfarin requirements. More frequent blood tests when starting levothyroxine can monitor a person’s response to the anticoagulant, allowing prompt adjustments as needed.

Patients taking both warfarin and levothyroxine and are already stabilized who then take another drug that reduces the levothyroxine effect (as discussed above), may have the anticoagulant’s effect decrease and thus be at increased risk of developing a blood clot.


In short

Levothyroxine interactions are commonly encountered in medical practice because levothyroxine is widely prescribed as are many other of the interacting drugs. But proper testing and dosage adjustments can prevent adverse outcomes. Those taking levothyroxine must be aware of these interactions, and take remedial action before any side effects occur.

Table. Drugs that interact with levothyroxine  

 Interactions that result in reduced levothyroxine absorption
 calcium carbonate (TUMS)
 calcium carbonate and magnesium hydroxide (ROLAIDS)
 aluminum hydroxide (AMPHOJEL) 
 iron supplements
 ferrous sulfate (FEOSOL, SLOW FE)
 cholesevelam (WELCHOL)
 raloxifene (EVISTA)**
 sevelamer (RENAGEL, RENVELA)
 sucralfate (CARAFATE)**
 ciprofloxacin (CIPRO)
 levofloxacin (LEVAQUIN)**
 lomefloxacin (MAXAQUIN)**
 moxifloxacin (AVELOX)*
 norfloxacin (CHIBROXIN, NOROXIN)**
 ofloxacin (FLOXIN)**
 Grapefruit Juice
 Interactions that result in increased levothyroxine metabolism, lower levels of in the blood
 carbamazepine (CARBATROL, TEGRETOL)
 oxcarbazepine (TRILEPTAL)
 phenobarbital (LUMINAL, SOLFOTON)**
 phenytoin (DILANTIN)
 primidone (MYSOLINE)
 efavirenz (SUSTIVA)
 nevirapine (VIRAMUNE)
 rifabutin (MYCOBUTIN)
 St. John’s wort
 imatinib (GLEEVEC)
 sertraline (ZOLOFT)**
 Interactions that result in changes of levothyroxine binding in blood
 Interaction that results in increased or decreased levels of other drugs
 warfarin (COUMADIN)


 * Do Not Use in Worst Pills, Best Pills
 ** Limited Use in Worst Pills, Best Pills