12/15/09 [Updated 2/5/10] A federal agency has updated warnings about the risk of liver toxicity for all products containing diclofenac, including a new recommendation that liver function be evaluated four to six weeks after starting treatment.  

Diclofenac is a nonsteroidal anti-inflammatory pain reliever that may be applied to the skin or swallowed. It is sold under the brand names Voltaren,  Cataflam and Flector. Diclofenac is also combined with misoprostal in the medication Arthrotec.

According to a spokeswoman for the Food and Drug Administration, the cautions, which resulted from an internal review, apply to both the pills and topical products, though the agency says it has only received reports of liver damage related to the pill forms of the drug through its Adverse Event Reporting System (AERS). 

As of March 18, 2005, the AERS database contained 146 U.S. cases of serious hepatotoxicity (liver toxicity) associated with diclofenac, including 32 cases of liver failure, which have resulted in transplants and deaths.

In a letter to doctors, Novartis Consumer Health and Endo Pharmaceuticals Inc., the companies that make and market a topical version, Voltaren Gel, wrote that its postmarket surveillance found borderline or greater elevations in liver injury tests occurred in 15 percent of diclofenac-treated patients, sometimes as early as the first month of use.

The company also advised that the best way minimize the potential risk for an adverse liver related event in patients treated with diclofenac sodium, is to use the lowest effective dose for the shortest duration possible.

Robert Shaw, MD, a rheumatologist at the Carroll County Arthritis and Osteoporosis Center in Westminster, Md., says physicians have long known to watch for liver damage in people who take diclofenac sodium pills, but that the new warnings make it clear that the gel also carries a risk.

“It’s especially a risk when patients come in and they’re on other medications that affect the liver or kidneys like statins. You’ve got to be aware that the gel can add to the side effect of these medicines,” he adds.

“As rheumatologists, we give methotrexate all the time. If you add the gel on top of that, even though there’s only a slight absorption, it is additive. That’s also true of the over-the-counter anti-inflammatories like Advil, Aleve and especially Tylenol,” Dr. Shaw says. “So I think the take-home message is – yes the gel has fewer side effects than diclofenac pills. But you still need to be ever vigilant to monitor for potential side effects, especially affecting the liver.”