Colchicine Interactions with Other Drugs Can Be Life-Threatening

In 2005, Worst Pills, Best Pills News warned readers about combining the gout drug colchicine with the antibiotic clarithromycin (BIAXIN), citing a study from Hong Kong suggesting that the combination can be fatal. But newer information about the mechanism of this interaction suggests that many other drugs may also be dangerous if combined with colchicine.                

How does colchicine interact with other medications?

The body treats drugs as if they were foreign chemicals (which they are), and the primary way the body tries to protect itself from too much colchicine is with a substance called P-glycoprotein (PGP). We have PGP in our intestines, liver, kidneys and brain, and the substance acts like a tiny pump to rid the body of certain drugs like colchicine.

Certain drugs, such as those listed in the table that accompanies this article, inhibit the function of PGP, which can result in increased levels of colchicine in the body and colchicine toxicity. In a sense, these drugs poison the pump that clears out the drug.

Other mechanisms for interaction between colchicine and drugs may also be involved, such as inhibition of colchicine metabolism.

What happens if colchicine levels get too high?

Too much colchicine in the body leads to toxicity. People with colchicine toxicity may experience fever, vomiting, diarrhea, abdominal pain and muscle pains.

Even worse, it can impair the bone marrow’s ability to make red and white blood cells, causing severe anemia and dangerously low numbers of white blood cells. When the number of white blood cells is reduced, your body may have difficulty fighting infections. Most people who have died from colchicine toxicity have had bone marrow toxicity or had preexisting kidney problems.

In the October 2005 issue of Worst Pills, Best Pills News, we discussed the dangerous interaction between colchicine and clarithromycin. In 88 patients admitted to the hospital because they had received both of these drugs, of those who received the two drugs together, nine (10.2 percent) died. Only one (3.6 percent) of the 28 patients who received the two drugs sequentially died.

What drugs have caused colchicine toxicity?

Although most cases of colchicine toxicity due to drug interactions have been caused by clarithromycin, any drug that is known to inhibit PGP function would be expected to interact with colchicine and increase the risk of colchicine toxicity. The table that accompanies this article lists drugs that are known to inhibit PGP function.

What You Can Do

Every patient on colchicine — whether on other drugs or not — should be alert for evidence of colchicine toxicity as described above.

The treatment for colchicine toxicity rests on symptomatic measures including gastric lavage (stomach washing/pumping); correction of fluid, electrolyte (salt) and protein loss; and management of bone marrow failure. Platelet transfusions may be required in patients at high risk for bleeding. Mortality rates remain high, despite respiratory and circulatory assistance in the critical care unit. Thus, due to the severity of colchicine toxicity and the difficulty in treating it after it occurs, prevention is crucial.

If you are taking colchicine, try to avoid any of the PGP-inhibiting drugs listed in the table. If it is necessary to use the PGP inhibitor, your physician may decide to stop the colchicine. Your physician also may take other measures to reduce the risk; for instance, in some cases, alternative medications can be used that do not inhibit PGP, such as substituting the antibiotic azithromycin (ZITHROMAX) for clarithromycin or erythromycin (EES, ERYTHROCIN).

If you are taking one or more of the PGP inhibitors in the table, starting colchicine in normal doses may cause colchicine toxicity. If the PGP inhibitor cannot be stopped, the risk of using colchicine may outweigh the potential benefit.

Also, if you are taking colchicine and want to add any other new drugs (prescription, nonprescription or herbal), check with your physician and/or pharmacist to make sure that the new drugs do not interact with colchicine.

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