Ministry of Health Tuesday 21 August 2007, 2:18PM
Media Release from the Ministry of Health
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COX-2 anti-inflammatory medicine Prexige have been revoked in New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,
Novartis, the pharmaceutical company sponsoring the medicine, is
issuing a recall notice to suppliers of the tablets today.
The decision has been reached by Medsafe after 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
"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
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
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:
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
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
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
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
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
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.