Call to extend NSAID warnings

EXPERTS have backed calls for a new warning label on non-steroidal anti-inflammatory drugs to caution against their use in people who are renally compromised for any reason.

In a letter to the MJA, Ronald Batagol, a Melbourne pharmacist, said the label should apply to all non-prescription NSAIDs, as well as the recently introduced labelling which warns of the renal risk of giving the drugs to children with dehydration due to diarrhoea or vomiting. (1)

Mr Batagol, who has written several books on drug safety, told MJA InSight he initiated the request for the TGA to change the labelling more than 4 years ago, and was pleased to see it recommended in May this year.

In his letter, Mr Batagol said the capacity for NSAIDs to cause renal damage even after short-term use in susceptible individuals was not as well appreciated as the drugs’ gastrointestinal side effects.
    
“It has been well documented that the use of NSAIDs in those who are fluid-depleted, including their short-term use in otherwise healthy individuals, can lead to renal failure, albeit reversible”, he wrote.

The label change — which applies to formulations of diclofenac, flurbiprofen, ibuprofen, ketoprofen and naproxen indicated for oral use in children — advises consumers to ask their doctor or pharmacist before using the medicine in children suffering from dehydration through diarrhoea and/or vomiting.

However, Mr Batagol said he wanted the new warning about renal risk also added to all NSAIDs, including adult formulations.

“We know that people who are renally compromised for any reason are at risk of kidney damage from the use of NSAIDs”, he wrote.

“This, of course, includes those taking some antihypertensive medications containing a diuretic, the well known ‘triple whammy’ effect.”

Associate Professor Stephen Alexander, consultant physician in paediatric nephrology at The Children’s Hospital at Westmead, Sydney, said the TGA’s decision to require new warning labels on NSAIDs for children was appropriate.

“There have been published case reports about NSAIDs causing renal failure in children”, he told MJA InSight.

While there was no long-term data, he said that he was aware of three paediatric cases of renal failure linked to rofecoxib (Vioxx) several years ago.

Professor Alexander cited a 2011 review in the journal Pediatrics which encouraged caution when using ibuprofen in children with dehydration or complex medical illnesses. (2)

The review stated:  “In children with dehydration, prostaglandin synthesis becomes an increasingly important mechanism for maintaining appropriate renal blood flow. The use of ibuprofen or any NSAID interferes with the renal effects of prostaglandins, which reduces renal blood flow and potentially precipitates or worsens renal dysfunction.”

Professor Alexander said four cases of renal toxicity linked to NSAIDs had also been reported in the Archives of Diseases in Childhood in 2007. All of the children had complex medical problems and all had an element of dehydration. (3)

In one case — a 13-year-old girl with relapse of Crohn’s disease who received diclofenac sodium per rectum — renal function remained mildly impaired 3 years later. In the other three cases, renal recovery was rapid and complete after stopping the NSAID and intravenously rehydrating the patient.

The case report authors said virtually all NSAIDs had been implicated in renal dysfunction, but indomethacin appeared to be associated with the highest risk and aspirin the lowest risk.

They qualified that “most cases of NSAID-induced renal impairment are mild and self-limiting” and said although their report did not prove cause and effect, further research was needed.

Dr Timothy Mathew, medical director of Kidney Health Australia, welcomed the call for additional label changes.

He said NSAIDs should also be avoided in renally compromised adults, including those taking diuretics and an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin receptor blockers.

“There are so many warnings on NSAIDs that the argument has always been that there’s no room left for any more, but there is a case for broader education on the risk of renal failure”, he told MJA InSight.

1. MJA 2014; 201: 381
2. Pediatrics 2011; 127: 580-587
3. Arch Dis Child 2007; 92: 524-526

(Photo: Kuttelvaserova Stuchelova / Shutterstock)