Prexige 200mg and 400mg tablets to be withdrawn

Media Release

21 August 2007

Prexige 200mg and 400mg tablets to be withdrawn in New Zealand

Consents allowing the supply of 200mg and 400mg tablets of the COX-2 anti-inflammatory medicine Prexige have been revoked in New Zealand by the Medicines and Medical Devices Safety Authority, Medsafe.

Novartis, the pharmaceutical company sponsoring the medicine, is issuing a recall notice to suppliers of the tablets today.

The decision has been reached by Medsafeafter it reviewed local and international safety data for Prexige relating to reports of severe liver damage in patients using this medication at doses of 200mg and above. In making the decision, Medsafe discussed the overall risks and benefits of the use of Prexige with medicines regulators in Australia, Singapore and the United Kingdom.

Medsafe's interim manager, Dr Stewart Jessamine, says Medsafe and the Medicines Adverse Reactions Committee (MARC) concluded that the data for higher doses of lumiracoxib, the active ingredient in Prexige, support an association with liver damage that was greater than that seen for other anti-inflammatory medicines.

"This increased risk of liver damage for Prexige outweighs any of the potential benefits claimed for the 200mg and 400mg dose," Dr Jessamine says.

"We, therefore, have revoked the consent of these doses. However, as there are no products containing 200mg of lumiracoxib marketed in New Zealand only the Prexige 400mg product will be recalled. We believe the recall will affect around 1000 patients who take Prexige 400mg tablets in New Zealand. Anyone who has general concerns should contact their doctor for advice in the first instance."

Medsafe also reviewed the safety of Prexige 100mg the product indicated for use in osteoarthritis.

"The data available from clinical trials and reported side effects in the United Kingdom, Europe, Canada or South America indicate that severe liver damage with Prexige 100mg/day is rare. The frequency with which liver damage is reported for Prexige 100mg does not appear to be significantly different from that seen for other anti-inflammatory medicines," Dr Jessamine says.

Medsafe has accepted the interim advice of the Medicines Adverse Reactions Committee (MARC) that Prexige 100mg should remain on the market and its safety be closely monitored.

To bring this into effect Medsafe has: decreased the maximum daily dose of Prexige to 100mg; limited the approved indication to the treatment of osteoarthritis; and added warning statements to the prescriber and patient information sheets for Prexige advising that patients should have blood tests to assess their liver function before starting treatment and every month thereafter.

"When taking a medicine you must take into consideration both the possible benefits and the potential risks as all medicines can cause severe side effects. Patients taking Prexige 100mg tablets for osteoarthritis should contact their doctor about having blood tests to check and monitor their liver function. I also encourage GPs to report any abnormalities found in these tests to the Centre for Adverse Reactions Monitoring at the University of Otago. Patients taking Prexige for acute pain should contact their general practitioner to discuss other analgesics that may be suitable," Dr Jessamine says.

Medsafe and the Medicines Adverse Reactions Committee (MARC) will continue to closely monitor the safety of Prexige 100mg tablets, and will review its ongoing availability in light of any new data that emerges.

In addition to the recall of Prexige 400mg, Novartis will provide written advice on the safety issues associated with Prexige to pharmacists and doctors. This advice will include the need to conduct monthly monitoring of patients’ liver function and to report any abnormalities to the Centre for Adverse Reactions Monitoring in Dunedin.

Further information is available on the Medsafe website: http://www.medsafegovt.nz/hot/alerts.asp

ENDS

Lucy Taylor Media Advisor, Ministry of Health
04 496 2349 / 027 687 5642

Questions and Answers

What is Prexige?
Prexige is a prescription medicine. It is not funded by PHARMAC. Prexige has consent in New Zealand as 100mg, 200mg and 400mg tablets. The Prexige range of products is approved for use in both Australia and New Zealand for the short-term treatment of acute pain at doses up to 400mg/day; and for the management of osteoarthritis at doses of 100mg/day.

Lumiracoxib, the active ingredient of Prexige, is a COX-2 inhibitor, and belongs to the same class of anti-inflammatory medicines as Vioxx, which was withdrawn worldwide in 2004 due to concerns about its cardiac safety.

What is the issue with Prexige?
The Therapeutic Goods Administration (TGA) of Australia revoked the registration of Prexige due to an increasing rate of reports of severe liver damage in patients taking this medication at doses of 200mg and above. The 8 cases reported in Australia associated with use of Prexige included 2 cases of death from liver failure and 2 patients requiring liver transplants.

Have any adverse reactions been reported in New Zealand?

The Centre for Adverse Reactions in Dunedin has received a total of 15 case reports of adverse reactions to lumiracoxib in the 2 years since it was approved. There are no reports of liver damage (hepatic injury) with this product in New Zealand.

How has the decision to withdraw consent for 200mg and 400mg doses been reached?

All anti-inflammatory medicines are known to cause liver damage and in rare cases use of these medicines can lead to severe side effects such as liver failure. Medsafe and the Medicines Adverse Reactions Committee (MARC) has evaluated safety data from the World Health Organisation (WHO); the Australian Therapeutic Goods Administration (TGA); and the pharmaceutical company Novartis to assess the possible association between use of Prexige and severe liver damage. Medsafe and the MARC concluded that there is evidence of a signal that lumiracoxib carries a risk of severe liver damage but that the strength of the association is unable to be defined on the basis of the currently available evidence. The data supports a clear association with higher doses of lumiracoxib, being 200mg and 400mg, but that for 100mg there is no evidence to suggest the risk of liver damage is higher than that found for other anti-inflammatory medicines. Following completion of its evaluation, Medsafe discussed its findings with the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom, the TGA and the medicines regulator in Singapore, before coming to a decision.

How are the consents withdrawn on the basis of the data evaluation?
Medsafe and the Medicines Adverse Reactions Committee (MARC) recommended that the consent for Prexige 200mg and 400mg tablets be revoked in New Zealand, under Section 35(1)(a) of the Medicines Act 1981, on the grounds that Prexige 200mg and 400mg tablets can no longer be regarded as medicines that can be administered or used safely for the purposes indicated in the application for consent. The Ministerial power to revoke consent under Section 35(1)(a) of the Medicines Act 1981 has been delegated to the Director-General of Health. Revoking consent of the 400mg tablets will necessitate a recall of stock distributed to pharmacy and wholesaler level.

Why are the 100mg tablets of Prexige still available?

The Medicines Adverse Reactions Committee (MARC) recognised that there is a clinical niche for this lower strength of Prexige for patients with osteoarthritis who have not found other treatments to be effective. Additionally, it is not yet clear whether the 100mg tablets carry the same risk of severe liver damage as the higher strength tablets. Medsafe and the MARC recommend that, at present, Prexige 100mg tablets should remain available in New Zealand for the treatment of osteoarthritis. However, to maximise the safe use of this medicine, Medsafe and the MARC recommended that the indications for Prexige be limited to management of osteoarthritis, and that new warning statements be added to the prescribing and consumer information sheets. In addition, it was recommended that Novartis issue a letter to all doctors in New Zealand, to advise them of the need to conduct monthly monitoring of patients’ liver function and to report abnormalities to the Centre for Adverse Reactions Monitoring in Dunedin.

How many patients are affected?

Data supplied by Novartis indicates that in the past 3 months 500-600 people per month have purchased 100mg/day packs of Prexige, and 1000-1100 patients per month have purchased packs of Prexige containing 10 tablets of 400mg strength.

What should patients on this medicine do?
Patients who are worried should contact their GP for advice. Patients taking Prexige for osteoarthritis should contact their GP about having a blood test to assess their liver function. Patients taking Prexige for acute pain should contact their general practitioner to discuss other analgesics that may be suitable.

How are patients and doctors being advised?
The medicine sponsor, Novartis, is issuing a recall for the 400mg Prexige tablets today and this includes writing to doctors and pharmacists.

What is happening in other countries?
Prexige remains on the market in the United Kingdom, Europe and Canada. Medicine regulatory authorities in these counties are also in the process of reviewing the safety data.

ends

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