Glucophage® (metformin) and iodinated contrast media

The Contraindications and Precautions sections in the FDA-approved package insert of the Bristol-Myers Squibb oral hypoglycemic drug Glucophage® (metformin) contain warnings about its use concomitant to the use of iodinated contrast agents. The reason for these warnings is not the presence of a direct drug-to-drug interaction; no such interaction occurs. Rather, the problem is that: 1) intravascular administration of iodinated contrast may cause acute renal failure in a small percentage of individuals, particularly those patients with preexisting, or a predisposition to, renal compromise (e.g., diabetics[!]), and 2) in patients with renal failure, Glucophage, which is excreted by the kidneys, may build up to dangerous levels, causing the potentially fatal condition of lactic acidosis.

The relevant portions of the Glucophage package insert read as follows:

In the CONTRAINDICATIONS section:
GLUCOPHAGE should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may cause acute alteration of renal function. (See also PRECAUTIONS).

In the PRECAUTIONS section:

Radiologic studies involving the use of iodinated contrast materials (for example, intravenous urogram, intravenous cholangiography, angiography and computed tomography (CT) scans with intravascular contrast materials) - Intravascular contrast studies with iodinated materials can lead to acute alteration of renal function and have been associated with lactic acidosis in patients receiving GLUCOPHAGE (see CONTRAINDICATIONS). Therefore, in patients in whom any such study is planned, GLUCOPHAGE should be discontinued at the time of or prior to the procedure, and withheld for 48 hours subsequent to the procedure and reinstated only after renal function has been re-evaluated and found to be normal.

There are three important points to take away from the specific wording of this Glucophage safety labeling:

1) The concern about the occurrence of renal compromise is primarily with iodinated contrast media, because these are the contrast media that carry a significant (though still fairly small) risk for contrast-induced acute renal failure. Current MR contrast agents carry very little (though not zero) risk of causing acute renal failure.

2) The concern is particularly with intravascular administration of iodinated contrast materials. It is only in the IV and angiographic procedures that rapidly administered large doses of iodinated contrast are presented to the kidneys, creating the circumstances that are favorable for renal failure. Small volume and slow-absorption procedures, like myelography and arthrography (which both involve parenteral, but not intravascular, administration), and oral cholecystography, raise little risk of renal failure. However, it would be prudent to temporarily suspend Glucophage use for these procedures as well.

3) The main new point is that there is not any need to stop Glucophage any significant time before contrast administration. The reasoning behind this is as follows:

a) presumably, Glucophage levels in the patient will be fine before the contrast study, so,

b) even if the patient goes into renal failure afterwards, and excretes no further Glucophage for awhile, those levels will simply remain fine unless the patient takes another dose. The important thing is to suspend Glucophage use after the contrast procedure until you are sure that contrast-induced renal failure will not occur. The reasonable time chosen for this observation period is 48 hours.

We hope that, armed with the full and latest package insert statements, and with an explanation of the circumstances of this issue, you'll be able to optimally manage your Glucophage patients who need contrast-enhanced radiographic procedures. If you require further information, or would like to obtain a Glucophage package insert, you may call the Bristol-Myers Squibb Glucophage hot line at 1-800-321-1335.