View Full Version : Warning for Prexige users
11-08-2007, 04:56 PM
What is it about the Cox 2 inhibitors? First Vioxx, then Celebrex, now Prexige (linked with potentially serious side effects). The article below suggests that Prexige is primarily prescribed for OA but I've had it prescribed as an anti-inflamm for shoulder and knee injury problems over the last 2 years and I know it's pretty commonly prescribed.
Thousands urged to have liver test
August 11, 2007 - 3:43PM
Up to 60,000 users of a drug, which caused the deaths of two Australians and two others to undergo liver transplants, have been warned to stop taking it immediately and undergo a liver function blood test.
The Therapeutic Goods Administration (TGA) today recalled the drug Prexige, used to treat osteoarthritis.
The TGA took less than 24 hours to deregister Prexige and order a recall after it reviewed eight cases where people suffered severe liver damage.
Two of the eight died and two needed liver transplants after using the drug.
Two of the eight cases emerged in March and the other six were revealed in the past six weeks.
"As a result of those case reports we have taken this straight to our drug safety committee who met yesterday...and they recommended that it immediately be deregistered,'' TGA principal medical adviser Rohan Hammett told AAP.
"It's important that patients cease taking the drug immediately and see their doctor to see if they have any liver damage and get advice about what else they should do.''
Prexige was first approved by the TGA in 2004, but has only been in common use since being listed on the Pharmaceutical Benefits Scheme last year.
Novartis Pharmaceuticals produces the drug, which is listed under the technical name Lumiracoxib.
Approximately 60,000 people take Lumiracoxib in Australia, which is prescribed for relief of osteoarthritis, post-operative pain, pain related to dental procedures and painful menstruation.
Dr Hammett said the level of severe cases in Australia was extremely low but the chance of liver damage increased the longer a person used the drug.
"It's important to note that the rate of the cases is still relatively rare...but we should note too that those are just the cases we know about,'' he said.
"There may well be many other patients out there who have a degree of liver damage that hopefully will get better when they stop the drug.''
Dr Hammett said Australia was the first country to recall Prexige, which is a Cox 2 inhibitor - a non-steroidal anti-inflammatory drug.
He said Vioxx, also a Cox 2 inhibitor, was voluntarily recalled worldwide by its manufacturer Merck in 2004 due to adverse health conditions in patients.
"Regulators around the world have been watching this class of drugs very closely since Vioxx and hence we've acted very quickly (over Prexige),'' he said.
Novartis Pharmaceutical Australia said it is "a pretty difficult time'' for the company and it supported the TGA's decision.
"Cleary, patient safety is of the utmost importance,'' Novartis Australia chief scientific officer Nick Kurstjens told AAP.
"And patients on Prexige should stop taking it immediately and contact their doctor to get advice on alternative medication.''
Mr Kurstjens said serious injury, including death, "is a known but rare serious side-effect for all Cox 2 inhibitors and traditional non-steroidal anti-inflammatory drugs.''
He also said its parent company Novartis AG, in Switzerland, had notified the relevant health authorities of the 50 countries where Prexige was sold.
"We're clearly going to be working with the health authorities, giving them the full information so that they can make the relevant decisions,'' Mr Kurstjens said.
More than seven million prescriptions have been issued since Prexige first hit the worldwide market in 2005.
But when asked if Novartis will act as Merck did over the Vioxx incident, Mr Kurstjens said ``no we're not - we're going on a case-by-case basis.''
People with inquiries about the withdrawal of Prexige can ring the TGA info line on 1800 004 599 or Novartis Pharmaceuticals on 1800 671 203.
11-08-2007, 06:41 PM
See front page article:
12-08-2007, 12:00 PM
It concerns me that claims about the effectiveness and reduced side effects of a medication (e.g., Novartis' claims about Prexige) come from the company that benefits from sales and not an idependent research body with nothing to gain.
I stopped taking Prexige (and Mobic) after a prolonged period of use (not at the same time) because of GI side effects and concern about the effect of taking that sort of medication over a prolonged period.
I've found the following herbal/health products just as effective (in terms of pain reduction for OA and other shoulder and knee issues) but without the negative side effects:
Glucosamine/Chondrotin (1500mg/1200mg) (Herron Osteoeze Active) - supposed to help noursh joint cartilage
Fish Oil - anti-niflamm, also has cardiovascular benefits (and great for skin, nails, hair!)
GNC Joint Formula (contains Curcumin, Boswelia, Ginger, Cats claw) - anti-inflamm
'Was taking the G/C and Fish Oil with Prexige or Mobic initially, then stopped taking Prexige / Mobic because of GI problems and immediately had an increase in pain. Then added the GNC joint formula and pain reduced almost straight away (within a week) - I've found it just as effective as Prexige or Mobic.
13-08-2007, 08:30 AM
Oops, forgot to mention....
With regard to Glucosamine/Chondroitin .. there is now plenty of evidence to confirm the benefits of this supplement for "joint health" (and, having used it for the last few years I can also attest to its benefits from a joint pain reduction/improved mobility point of view).
A word of warning however...... my physio (who is a researcher in addition to practicing physio) recently told me that there is new evidence to suggest that G/C can reduce fertility and that it should be avoided if that is a concern for you.
14-08-2007, 01:26 PM
Australia pulls Novartis painkiller Prexige on liver concerns
By Anita Greil
Last Update: 9:04 PM ET Aug 12, 2007
ZURICH (MarketWatch) -- Australia's drugs regulator Saturday canceled the registration of Novartis AG's (NVS : novartis a g sponsored adr
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NVS53.59, -0.95, -1.7%) Prexige, a painkiller that belongs to the same type of drugs as Vioxx, after receiving reports of serious liver damage in patients taking it.
Australia's regulator, the Therapeutic Goods Administration, or TGA, canceled the registration of Prexige, also known as lumiracoxib, because of serious liver-related side effects associated with the use of the drug.
As of August 10, the regulator had received eight reports of serious liver-related adverse reactions to the drug, including two deaths and two liver transplants, said Dr. Rohan Hammett, the agency's principal medical adviser, in a statement.
Prexige belongs to a class of drugs known as Cox-2 inhibitors. These drugs were designed to be easier on the stomach than older pain pills such as ibuprofen and naproxen, which are associated with gastric bleeding in some patients. But several of the Cox-2 drugs became mired in safety issues in recent years.
Merck & Co. (MRK : Merck & Co., Inc
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MRK50.56, -0.32, -0.6%) withdrew Vioxx from the global market in the fall of 2004 after a study showed it elevated patients' risk of heart attacks and strokes. In April 2005, Pfizer Inc. (PFE : Pfizer Inc
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PFE23.89, -0.10, -0.4%) pulled its Bextra pain reliever from the global market amid concerns over its heart risks. Merck and Pfizer are still fighting big lawsuits from patients who took the pills. In the U.S., Pfizer's Celebrex is the only Cox-2 remaining on the market.
Prexige was first approved in Australia in July 2004, but has only recently become widely used since it became eligible for reimbursement, meaning that patients using it don't have to pay for the drug out of their own pocket. "It seems that the longer people are on the medicine, the greater the chance of liver injury," Hammett said. "The TGA is, therefore, advising people to stop taking the lumiracoxib immediately and to discuss alternative treatments with their doctor."
Novartis is collaborating with the Australian regulator, but continues to believe that Prexige has a positive benefit/risk profile in the treatment of appropriate patients with osteoarthritis and acute pain, spokesman John Gilardi said.
Before the Vioxx controversy, Novartis had expected Prexige to become a multi-billion dollar product. The company lowered its expectations for the drug's sales potential after the entire class of drugs came under pressure two years ago, but as recently as this year maintained hopes that Prexige could achieve annual sales of $1 billion, if it were approved in the U.S.
The Food and Drug Administration will decide on approval for Prexige in late September, but most analysts are doubting that the drug will win the U.S. regulator's OK.
Novartis is in the process of rolling out the drug in the European Union, where it received approval last year. Swiss approval for the drug is still pending.
Australia was one of the first countries to approve the drug, which is why it's been sold there at a higher dose than in countries where it was filed later, and after studies showed that the lower dose is as effective but has less side effects.
"The 100 mg dose of Prexige, which is the recommended dose worldwide for treatment of osteoarthritis, hasn't been associated with an unexpected incidence of liver-related side effects," Novartis said.
Since Prexige was first launched, more than seven million prescriptions have been issued worldwide, according to estimates, Novartis said. The drug achieved worldwide sales of $52 million in the six months to June 30, Gilardi said.
Novartis has suffered a number of setbacks this year, including an estimated three-year delay in another potential multi-billion dollar drug, the diabetes treatment Galvus. In March, Novartis was forced to suspend sales in the U.S. of another growth driver, the bowel drug Zelnorm. The drug has since been allowed to go back on sale, although with heavy restrictions. Then Novartis lost a court battle with TEVA Pharmaceuticals (TEVA : teva pharmaceutical inds ltd adr
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TEVA43.14, -0.19, -0.4%) , which is challenging the patent of heart drug Lotrel, and was given permission to go ahead selling it in the U.S., although patent litigation is still ongoing.
Novartis shares closed at CHF64.95 on Friday. The stock has fallen more than 6% so far this year. Like other large pharmaceuticals companies it has underperformed the sector average, which was up due to a strong performance of many of the regions's smaller pharmaceutical companies.
Company Web site: http://www.novartis.com
14-08-2007, 01:29 PM
Prexige warning; no recall here
A drug recall in Australia has not prompted authorities here in New Zealand to follow suit. Australian drug authorities have pulled the pain relief and osteoarthritis drug Prexige from the shelves..
It has been discovered the drug, which is used here, can increase the risk of liver damage.
MedSafe spokesman Stewart Jessamine says they are concerned, and if people are on this medicine they should talk with their doctor because there are other safer options available that do not have the same side effects. Dr Jessamine says in the meantime his people will be collecting data and working out the most appropriate advice for New Zealanders.
Dr Jessamine says liver damage has been found only in people who use the drug long-term. He says most New Zealanders use the drug for less than 10 days at a time. And he says only about 2000 people in New Zealand are on the drug.
The distributors of the drug here have yet to make a move.
14-08-2007, 01:32 PM
Novartis pain drug battles Vioxx stigma
Novartis' Prexige approved in EU, but similarities to Vioxx could present a hard time getting past the FDA.
By Aaron Smith, CNNMoney.com staff writer
November 7 2006: 1:31 PM EST
NEW YORK (CNNMoney.com) -- Novartis plans to bring a new arthritis painkiller to the U.S. market, but analysts say its similarity to the disgraced drug Vioxx could kill its chances of becoming a billion-dollar blockbuster.
The Swiss drug giant Novartis AG (up $0.32 to $61.55, Charts) said Tuesday that its painkiller Prexige was given a green light in the European Union for the treatment of arthritis. Novartis plans to "resubmit" the drug to the Food and Drug Administration in 2007, following the agency's request for more information in 2003.
Compared to Vioxx from Merck & Co., Inc., (up $0.33 to $46.14, Charts) Prexige has a better profile with regard to heart attack and stroke risks. Nonetheless, the drug is a member of the Cox-2 inhibitor class of drugs -- the same as Vioxx -- and could have a hard time winning the approval of American doctors and patients, not to mention the FDA.
"Doctors will be afraid to use this drug and ultimately that's what limits its potential," said Gbola Amusa, analyst for Sanford C. Bernstein. "Even when it's approved, doctors will see a safety issue with the drug and not use it as much."
The big threat to Big Pharma
Novartis spokeswoman Sherry Pudloski said that clinical trials have shown that Prexige is 79 percent better in terms of gastric bleeding than the NSAIDs, with a "comparable level" of cardiovascular risk. In theory, this presents Prexige with an iron-clad profile, as it would have reduced risks of heart attacks, strokes and stomach bleeding.
But despite its solid safety profile, the Vioxx stigma could prevent Prexige from becoming a billion-dollar blockbuster, analysts said.
"By no means does it have blockbuster potential," said Amusa of Bernstein, estimating annual sales of less than $500 million.
"I think that blockbuster is an optimistic assessment," said Les Funtleyder, analyst for Miller Tabak. "In the right population, this is a good drug, except the right population isn't everybody with a pain. The right population is people with severe problems who also have stomach issues. Obviously, the [drug] class comes with some baggage."
Novartis originally submitted Prexige years ago, but the review process was stymied on Sept. 30, 2004. That is Merck's day of infamy, when the company pulled its arthritis painkiller Vioxx off the market after a study showed that the drug increased the risk of heart attacks and strokes. Not only did Merck bid adieu to $2.5 billion in annual sales, but more than 20,000 lawsuits have been filed against the No. 4 U.S. drugmaker since that time. Thousands of former Vioxx patients and their family members blame the drug for their heart attacks, fatal and non-fatal.
The Cox-2 scandal also affected Pfizer Inc (up $0.30 to $27.29, Charts)., the biggest drugmaker in the world. At the request of the FDA, Pfizer took its arthritis painkiller Bextra off the market, losing $1.3 billion in annual sales. But Pfizer's other arthritis painkiller, Celebrex, was never taken off the market.
Clock ticking for Celebrex's U.S. monopoly
Celebrex is the only Cox-2 inhibitor available to U.S. patients and Pfizer is on track to meet its blockbuster sales goal of $1 billion for the year. But that pales in comparison to the Celebrex sales tally of $3.3 billion in 2004. The drug's sales are affected by the Cox-2 stigma. In July of 2005, the FDA made Pfizer add a "black box" warning, the most severe type of warning, to its Celebrex label to reflect risks of heart attacks, strokes and gastrointestinal bleeding.
Vioxx, Celebrex, Bextra and Prexige are all Cox-2 inhibitors. These anti-inflammatories kill pain by reducing swelling in arthritic joints. They have been marketed and prescribed (until 2005, in the case with Celebrex) as easy-on-the-stomach alternatives to over-the-counter members of the non-steroidal anti-inflammatory drugs (NSAID), like ibuprofen and naproxen, which have been linked to stomach bleeding. This class includes Aleve from the German drugmaker Bayer (up $0.10 to $51.45, Charts).
A hard sell to the FDA
Amusa, the Bernstein analyst, said "if there's any other Cox-2 that's going to overcome the safety issues, it's going to be Prexige." But it will still be a hard sell with the FDA, he said, because the agency is trying to repair its reputation from approving Vioxx.
"The FDA is certainly more conservative now than [the European regulators,]" said Amusa. "Let's not forget that they're the ones that got blamed for Vioxx. They don't want to get embarrassed twice. Ultimately, the FDA is going to be very, very cautious here."
14-08-2007, 01:51 PM
Shows that liver abnormalities have been previously recognised in Prexige
16-08-2007, 06:17 PM
Shows that liver abnormalities have been previously recognised in Prexige
I am led to believe that the reason Prexige had been rejected for registration in the USA was because the FDA had actually questioned its liver risk profile and was awaiting more data on this. So you can only assume this risk was widely known?
The problems seem to arise with prolonged daily use, pretty much as they do with most NSAID's.
16-08-2007, 07:02 PM
The problems seem to arise with prolonged daily use, pretty much as they do with most NSAID's.[/QUOTE = Stravious]
... as well as high dosages (according to the reports indicated above).
[QUOTE=Stravious]I am led to believe that the reason Prexige had been rejected for registration in the USA was because the FDA had actually questioned its liver risk profile and was awaiting more data on this. So you can only assume this risk was widely known?
Silly really, for patients to assume that patient health might be more important than billion dollar plus yearly profits. Whatever were we thinking!?
P.S. At a check up today, my GP told me that she'd also found seriously elevated liver enzyme (?) levels in a patient taking Prexige. (She ordered a blood test for something else, was alarmed when she saw the liver enzyme levels and, on investigation, discovered that Prexige was causing it)
20-08-2007, 08:29 PM
Drug safety watch questioned
Australian. Clara Pirani reports | August 18, 2007
ARTHRITIS sufferers could be forgiven for thinking they were experiencing deja vu when they picked up the Sunday newspapers last week. Less than three years after one of the most popular arthritis drugs in Australia was withdrawn after being found to increase the risk of heart attack, headlines claimed that yet another arthritis treatment was being recalled after some patients taking the drug died from liver failure.
The Therapeutic Goods Administration had received eight reports of liver damage in patients taking Prexige, a painkiller used by 60,000 Australians to treat osteoarthritis. The reports included two deaths and two people who required liver transplants.
"The TGA and its expert advisory committee, the Adverse Drug Reactions Advisory Committee, have urgently investigated these reports," the TGA said last Saturday. "ADRAC has today recommended the cancellation of the registration of Lumiracoxib (Prexige) due to the severity of the reported side effects associated with this drug."
While clinicians applaud the TGA's quick action in taking Prexige off the shelves, some claim the case raises questions about how drug safety is monitored in Australia.
Prexige was first sold in Australia in November 2005 but was only widely used after it was listed on the Pharmaceutical Benefits Scheme in August 2006.
The TGA and various medical groups were watching the drug closely for any signs of serious side effects. The National Prescribing Service had gone so far as to publicly state that Prexige should not be listed on the PBS.
Prexige is a Cox-2 inhibitor, one of the new-generation non-steroidal anti-inflammatory drugs (NSAIDs) known to cause fewer side effects -- such as gastric bleeding -- than older anti-inflammatory drugs. However, concerns about Cox-2 inhibitors emerged in September 2004 when pharmaceutical giant Merck withdrew Vioxx, a popular Cox-2 used to treat arthritis, after it was found to increase heart attack and stroke risk.
Then in April 2005, drug company Pfizer withdrew its painkiller Bextra amid concerns that it also was linked to heart disease.
A day before Prexige was listed on the PBS last year, the National Prescribing Service warned there was insufficient information about the drug's safety. "We are warning all GPs that its long-term safety hasn't been proven yet," a NPS spokesman said.
Clinicians were monitoring the drug for cardiac side effects, but no one expected severe, even fatal, liver damage.
"We were aware of cardiac risks associated with this class of drugs," said Lynn Weekes, CEO of the National Prescribing Service. "But these effects on the liver have really come out of the blue. Some side effects are only really seen over time, when a drug is more widely used."
A spokeswoman for Novartis, which makes Prexige, said liver damage was a known but rare side effect of the drug.
Prior to its release, the largest Prexige clinical trial was the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET). TARGET was a one-year trial involving more than 18,000 patients with osteoarthritis that compared a 400mg dose of Prexige to the NSAIDs naproxen (500mg twice-daily) and ibuprofen (800mg three times-daily).
Participants were given a 400mg dose of Prexige once daily for one year.
"This study demonstrated that Prexige had a superior gastro-intestinal safety profile, providing a significant 79 per cent reduction in serious gastro-intestinal complications in patients not taking aspirin compared with traditional NSAIDs (ibuprofen and naproxen)," a Novartis spokeswoman said.
"No statistically significant difference was seen in liver safety between Prexige and the NSAIDs in this study. In this trial, nine cases were judged as probable or possible drug-induced clinical hepatitis: six on Prexige and three on NSAIDs (two on ibuprofen and one on naproxen). All patients recovered fully after treatment was halted."
However, some argue the case proves that companies should be required to conduct studies of drugs after they are approved -- known as post-marketing studies -- because clinical trials will only detect a limited number of side effects.
Lyn March, president of the Australian Rheumatology Association and a rheumatologist at Royal North Shore Hospital, says clinical trials are not set up to test for rare side effects that could occur once a drug is widely used by the public.
"People who volunteer for trials are generally healthy and trials have exclusion criteria for people who already have underlying health problems. And I would imagine that if people develop health problems, like unusual side effects either from the drug or the placebo, they would be dropped from the trial."
The spokeswoman for Novartis said serious liver side effects had been reported rarely for all Cox-2s and non-steroidal anti-inflammatories.
The TGA's principal adviser Rohan Hammett agrees that clinical trials will only detect common side effects, not rare adverse events occuring once a drug is widely used.
"With any drug, the pre-registration trials that are done usually involve between 300 and 500 patients. They are designed to pick up major safety problems that occur at a rate of about 1 in 1000 patients. So anything that happens less frequently than that won't be picked up until the drugs are available on the market."
March would like to see additional testing of drugs before they are listed on the PBS.
"None of these drugs really gets used widely until they are listed on the PBS. I would definitely support increased pharmaco-vigilance in some way."
Lynn Weekes agrees.
"Some side effects are only really seen over time when the drug is more widely used. That's why post-marketing studies are really essential, not just in terms of a drug's safety but also usage. There were studies done initially on the drug (Prexige) up to 400mg, and there was no evidence of liver damage."
According to the TGA, companies are not routinely required to conduct post-marketing studies. However, the TGA can require companies to conduct a post-marketing study as a condition of registration.
The TGA also expects to be informed of the results of any post-marketing safety studies being conducted by a company, whether or not done in response to a request from a regulator.
Drug companies are legally required to report all serious suspected adverse reactions to the TGA/ADRAC, where "serious" is defined as "a reaction that results in death, is life-threatening, results in hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, is a congenital anomaly, or is an other medically important event or reaction".
Doctors are not legally required to report suspected adverse drug reactions to the TGA or ADRAC. However, up to a third of the approximately 10,000 reports of adverse reactions received by TGA each year come directly from general practitioners.
Novartis says it does monitor some of its drugs after they are approved.
"Novartis Australia conducts post-marketing trials on some medications, however these trials are not designed for the sole purpose of collecting adverse-event data," the spokeswoman said.
Chris Kelman, associate professor in population health at the Australian National University, says the current drug regulatory system is outdated and relies on a process of pre-marketing evaluation, followed by periodic reviews of reported adverse events.
Writing recently in the Medical Journal of Australia (2007;186(5):249-252), Kelman proposes a new provisional licensing system that would restrict the use of newly approved drugs until post-marketing data is collated and assessed.
"All applications for new chemical entities would continue to be evaluated by the TGA; however, initial provisional approval would provide a 'Caution -- New Medicine' rating for the drug and have expanded requirements for periodic review.
"Periodic review would be based on accumulated adverse drug reaction reports, recent drug studies, and commissioned Australian observational studies using linked databases. Provisional approval could be upgraded once significant market experience is gained; for example, a medicine could be given a 'gold' safety rating after achieving an agreed benchmark."
Hammett says the TGA sometimes requires companies requesting approval for a new drug to provide ongoing surveillance to ensure consumers are not experiencing any unexpected side effects.
However, the requirements do not apply to all new drugs.
"The 20th version of a blood pressure drug won't have the same requirements because the side effects profile has already been well established," Hammett says. "It's tailor-made according to the risk of the product."
Hammett says the TGA's swift withdrawal of Prexige shows the current system for reviewing drugs is working.
Prexige is available in more than 50 countries around the world, but Australia is the only country to withdraw the drug. Now other national regulators are asking the TGA to share its data.
Hammett says the TGA had closely monitored the drug, knowing that it was relatively new and belonged to a class of drugs that had previously caused dangerous side effects.
"The TGA and the Government were aware of that with this drug, and had discussions with the sponsor about an enhanced post-market vigilance program.
"Novartis, in fact, had a worldwide post-market safety program in place. They are doing ongoing clinical trials internationally, and are sharing that data with us and that was specifically because there was a concern about this class of drug and we wanted to make sure that we had adequate post-market safety measures in place.
20-08-2007, 08:29 PM
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