NEWS - Nexium (esomeprazole) for reducing risk of NSAID ulcers

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Esomeprazole (Nexium) for reducing risk of NSAID ulcers

Rheumawire

December 7, 2004

Wilmington, DE - The proton pump inhibitor (PPI) esomeprazole (Nexium,

AstraZeneca) has been approved by the US FDA for the new indication of

reducing the risk of gastric ulcers in patients on continuous therapy

with nonsteroidal anti-inflammatory drugs (NSAIDs). The agency also

issued an " approvable " letter for the indication of healing gastric

ulcers associated with NSAID therapy.

Similar indications were recently approved in Europe. The product

successfully completed the EEC Mutual Recognition Procedure in September

and is now awaiting individual national approvals, for 2 indications -

prevention of both gastric and duodenal ulcers associated with

continuous NSAID therapy in patients at risk and the healing of gastric

ulcers associated with continuous NSAID therapy.

Esomeprazole is " effective in substantially reducing NSAID-associated

damage and ulcers, " says Prof Hawkey (University Hospital,

Nottingham, UK), lead investigator of the worldwide esomeprazole NSAID

program, in a press release issued by AstraZeneca. The reduction in

dyspepsia and ulcers was seen both with traditional nonselective NSAIDs

and with selective COX-2 drugs, he adds.

" The advantages of combining a proton pump inhibitor with NSAIDs remain

underappreciated, " says Dr Mark Fendrick (professor of internal

medicine, University of Michigan, Ann Arbor), whom rheumawire approached

for comments. Fendrick has devised a matrix offering guidance on the use

of NSAIDs and coxibs, as previously reported by rheumawire, and has

recently published an update in the wake of the rofecoxib (Vioxx, Merck)

withdrawal [1]. He has consulting agreements with several pharmaceutical

companies, including manufacturers of COX-2 inhibitors, PPIs, and

non-NSAID pain and inflammation therapies.

" I am hopeful that this FDA approval for the use of another proton pump

inhibitor in patients taking NSAIDs will bring more attention to this

very useful combination, " Fendrick commented in an interview.

The other PPI that already has a similar claim is lansoprazole

(Prevacid, TAP Pharmaceuticals), which is indicated for the healing and

risk reduction of the recurrence of gastric ulcers associated with

NSAIDs in chronic NSAID users. Late last year, a combination product

containing lansoprazole and naproxen was launched in the US (Prevacid

NapraPac, TAP Pharmaceuticals).

The 3 other PPIs also marketed are pantoprazole (Protonix, Wyeth),

rabeprazole (Aciphex, Eisai), and omeprazole, the original of these

agents, which is now available generically and also over-the-counter in

many countries, including the US (the OTC brand is Prilosec, marketed by

AstraZeneca and Procter & Gamble). None of these other 3 products have

claims for NSAID-induced gastrointestinal damage, although there have

been studies with omeprazole in this patient population, Fendrick

comments. As they are all products in the same class with the same

mechanism of action, they would all be expected to work, and it is

" unlikely that one PPI would show a clinically meaningful advantage over

another in its ability to reduce NSAID adverse events, " he says.

The PPIs are superior to H2 antagonists in offering protection against

NSAID-induced damage, Fendrick comments. There are randomized studies

showing superiority of the PPIs in both the healing of NSAID-associated

ulcers and demonstrating superior prevention of recurrence of these

ulcers. The PPIs are also a better option than the gastroprotective

agent misoprostol (Cytotec, Searle) in many circumstances, Fendrick

says, adding that this prostaglandin product is little used in the US.

The protection misoprostol offers against NSAID-induced damage is

" roughly equivalent " to that seen with the PPIs, but it has 2

disadvantages - it needs to be taken 4 times daily (vs once daily with

PPIs) and is associated with GI side effects of bloating and diarrhea,

which put patients off using it, he says.

The combination of a PPI with a traditional nonselective NSAID is

particularly useful in patients who are also taking low-dose aspirin for

cardioprotection, says Fendrick. " It remains unappreciated, despite

convincing clinical trial data, that in patients taking aspirin, the

gastrointestinal advantage of a selective COX-2 inhibitor over a

traditional NSAID is seriously reduced and may even be negated, so in

this population, the combination may be more appropriate than a coxib. "

Fendrick adds that, to date, there are little data examining the

GI-reducing properties of combining a PPI with a coxib - the " double

whammy " - and it remains unclear how this combination compares with

alternatives, both in patients taking low-dose aspirin and those who

aren't.

For patients who aren't taking aspirin for cardioprotection, the

combination of a traditional NSAID with a PPI has the potential to be a

better option than a coxib, Fendrick maintains. The combination has been

shown to provide " close to equal levels of gastroprotection " in 1

randomized trial in high-risk patients and likely provides a greater

reduction of NSAID-related dyspepsia, which is far more common although

less clinically serious than the GI damage associated with NSAIDs, he

says. And the combination can work out costing the same or even less

than a coxib, depending on which products are used.

In his most recent update, Fendrick discusses how the withdrawal of

rofecoxib has affected the decisions that now need to be made about

prescribing NSAID therapy. " Clinicians should balance the benefits and

risks of available agents in terms of pain relief and cardiovascular and

gastrointestinal safety, " he writes. " Until the burden of safety is met,

we should consider taking our patients 'back to the future' and use

older, well-studied agents to provide symptomatic relief. "

Zosia Chustecka

Source

1. Fendrick AM. COX-2 inhibitor use after Vioxx: Careful

balance or end of the rope? Am J Managed Care 2004, 10:740-741.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org