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1.
VALDECOXIB
Label
revised to reflect hypersensitivity reactions and skin reactions
USA.
Pharmacia and Pfizer have updated the Warnings section in the product
label for valdecoxib tablets (Bextra) to include hypersensitivity
reactions (anaphylactic reactions and angioedema) and skin reactions
including Stevens-johnson syndrome, toxic epidermal necrolysis,
exfoliative dermatitis and erythema multiform as possible adverse
reactions with the product. The Contraindications section advises
that valdecoxib (Bextra) should not be given to patients who have
demonstrated allergic-type reactions to sulfonamides. These updates
are based on postmarketing surveillance reports of such reactions
occurring with valdecoxib (Bextra) in patients with or without a
history of allergic-type reactions to sulfonamides. In the
US, valdecoxib
(Bextra) is indicated for the relief of signs and symptoms of osteoarthritis
and adult rheumatoid arthritis, and for the treatment of primary
dysmenorrhoea.
Reports in WHO file:
Face oedema 1, oedema peripheral 1
Reference:
'Dear Healthcare
Professional' letter from Pharmacia Corporation and Pfizer Inc,
13 Nov 2002. Available from URL: http://www.fda.gov
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2.
CYCLO-OXYGENASE (COX)-2
INHIBITORS
Reports
of hepatotoxicity
New
Zealand. Seventeen reports
of hepatotoxicity have been received as part of the IMMP (Intensive
Medicines Monitoring Programme) monitoring of selective COX-2 inhibitors,
including three reports of significant liver injury in patients
aged 85, 81 and 61 years, who received rofecoxib for 7 days to 3
months before developing liver injury, ranging from markedly elevated
liver transaminase levels to biopsy-confirmed severe
cholestatic hepatitis. There were also three similar reports of
liver injury in patients receiving celecoxib, although the association
was less clear due to concomitant medications. The remaining reports
involved mild liver function abnormalities with celecoxib (n = 8)
and rofecoxib (3). The IMMP reports of hepatotoxicity with COX-2
inhibitors suggest that 'this type of reaction is an uncommon class
effect of all NSAIAs (nonsteroidal anti-inflammatory agents), both
COX-2 specific and non-specific'.
Reports in WHO-file:
Coxibs; Liver and biliary system disorders 891
Reference: 
Prescriber
Update 24(1): Jun 2003. Available from URL: http://www.medsafe.govt.nz
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3.
CELECOXIB, ROFECOXIB
Neuropsychiatric
events
Australia.
Acute neuropsychiatric reactions may be a class effect of the COX-2
inhibitors, according to the Australian Adverse Drug Reactions Advisory
Committee (ADRAC). ADRAC has received 142 reports of acute neuropsychiatric
reactions associated with celecoxib (Celebrex) and 49 reports associated
with rofecoxib (Vioxx). The most common reactions associated with
celecoxib were confusion (23 reports), somnolence (22) and insomnia
(21), while the most common reactions associated with rofecoxib
were confusion (16) and hallucinations (11). In many cases the onset
of the event occurred within 24 hours of the first dose of the drug,
although some cases occurred following re-exposure.
Reference:
Australian
Adverse Drug Reactions Bulletin 22, Feb 2003.
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4.
ROFECOXIB, CELECOXIB
Case
reports support causal association with liver toxicity
New
Zealand. The recently
published IMMP (Intensive Medicines Monitoring Programme) Prescriber
Update Article on COX-2 inhibitors warns that, as with other Cyclooxygenase
(COX) - inhibitors, liver toxicity may occur with celecoxib and
rofecoxib. 17 reports of hepatotoxicity were received by the IMMP
as part of the monitoring of COX-2 inhibitors. In most reports,
the onset time was less than three months. Three were case reports
(one woman aged 85 years and two men aged 81 and 61 years age) of
significant liver injury occurring in association with rofecoxib.
The other case reports included other known hepatotoxic medicines.
While the clinical details concerning these case reports were not
complete and the clinical investigations reported were not exhaustive,
it is probable that these hepatic events were related to rofecoxib.
There were three other reports of similar toxicity involving celecoxib
where the causal relationship was less clear due to concomitant
hepatotoxic medicines including methotrexate and leflunomide. In
addition, there were 8 reports of mild liver function abnormalities
with celecoxib and three with rofecoxib. Two of these patients recovered
following withdrawal of the COX-2 inhibitor but the outcome of the
others is unknown. Dr David Coulter, Director IMMP writes that hepatotoxicity
is reported infrequently in literature; the IMMP reports suggest
that this type of reaction is an uncommon class effect of COX-2
specific and non specific non steroidal antiinflammatory agents.
COX-2 inhibitors should be discontinued in patients with signs or
symptoms that suggest liver dysfunction.
Reference:
Prescriber
Update Articles, Apr 2003. Available from URL: htto://www.medsafe.govt.nz
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5.
Counterfeit Artesunate Antimalarial Tablets
Dr.
Paul Newton, Centre for Clinical Vaccinology and Tropical
Medicine, Churchill Hospital,
Old Road, Oxford
OX3 7U, England,
UK
Artesunate is a vital life-saving
antimalarial drug, developed in China, and now used extensively in 'South-East Asia for the treatment of falciparum malaria.
It is also commonly available from the private sector. In the late
1990s counterfeit artesunate appeared in the region and has been
disseminated from Vietnam to Burma
(Myanmar).
In 1999-2000 up to 38 % of artesunate, labelled as manufactured
by Guilin Pharma, People's Republic of China, bought in pharmacies
and shops in Burma, Laos, Cambodia, Vietnam and on the Thai/Burma
border contained no detectable artesunatel-2. This has
led to the deaths of an unknown but substantial number of people
who would otherwise have survived their malaria infection3.
A simple, inexpensive Fast-Red dye test allows one to reliably check
the authenticity of artesunate tablets4. The first 'generation'
fakes, which bear a grey sticker rather than a true hologram, are
relatively easy to distinguish from the genuine product but remain
in circulation in South-East Asia.
However, two further sophisticated
'generations' of counterfeit artesunate, labelled as produced by
'Guilin Pharma', have recently been found in Laos and Cambodia with
new, convincing and very well crafted but fake holograms attached
to the blisterpacks (see figures below. Also see www.shoklo-unit.com)5.
The second 'generation' hologram is a true hologram and only appears
to differ from the genuine hologram in the shape of mountain outline
and the lack of the microscopic legend 'Guilin Pharma' printed below
the 'waves'. The printing on the blisterpack is not clear. All have
the same code, and manufacture and expiry dates (code '00902' and
manufacture and expiry dates of '09/00' and '09/03', respectively)
.
The third generation hologram
has a mountain outline similar to the genuine Guilin
product but lacks the microscopic legend 'Guilin Pharma' printed
below the 'waves'. The printing on the blisterpack is crisp and
similar to that on the genuine product, bearing the code '010901'
with manufacture and expiry dates of '09/01' and '09/04', respectively.
It is likely however that artesunate with these 2nd and 3rd 'generation'
fake holograms have or will be made with different dates and codes.
All 'artesunate' blisterpacks with the 2nd and 3rd generation fake
holograms were negative for artesunate by the Fast-Red Dye Test
and contained no artesunate on HPLC analysis. It is feared that
counterfeit artesunate blisterpacks bearing the new sophisticated
fake holograms are widely distributed in Asia, and perhaps Africa,
but because of their similarity to the genuine product they are
unrecognised by pharmacists, health staff and patients. There are
also reports of fake intramuscular artemether, used to treat patients
with severe falciparum malaria, labelled as produced by Kunming
Pharmaceuticals (Kunming, PRC) in Burma (Myanmar) (New Light of
Myanmar, Rangoon, Myanmar; electronic edition, 9th November 2001).
There is an urgent need for
action and we hope that this information might prompt interventions
to combat this under recognised serious public health problem.
Reference
- Rozendaal
J. Fake antimalarials circulating in Cambodia.
Bull Mekong Malaria Forum 2000;
7: 62- 68.
- Newton
PN, Praux S, Green M, Smithuis F, Rozendaal J, Prakongpan S, Chotivanich
K, Mayxay M, Looareesuwan S, Farrar J, Nosten F, White NJ. Fake
artesunate in southeast Asia. Lancet 2001; 357: 1948-1950.
- Newton
PN, Rozendaal J, Green M, White
NJ. Murder by fake
drugs - time for international action. British Medical Journal
2002; 324: 800 - 801.
- Green
MD, Mount DL,
Wirtz RA. Authentication of artemether, artesunate and dihydroartemisinin
antimalarial tablets using a simple colorimetric method. Trap.
Med. Int. Health 2001; 6: 980-982.
- Newton
PN, Dondorp A, Green M, Mayxay M, White NJ
(in press). Fake artesunate antimalarials in southeast Asia. Lancet
Genuine artesunate hologram
Counterfeit artesunate hologram
-2nd generation
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6.
MOROCTOCOG ALFA
Report
of lack of effect in prophylaxis patients
Canada.
Wyeth Canada
is informing physicians of changes to the Precautions and Adverse
Reactions sections of the product monograph for moroctocog alfa
(Refacto, Recombinant Anti-haemophilic Factor). Moroctocog alfa
(Refacto, Antihaemophilic Factor Recombinant) has been licensed
in Canada since 2002 and is indicated for the control and prevention
of haemorrhagic episodes and for routine and surgical prophylaxis
in patients with haemophilia A. Reports of lack of effect, mainly
in prophylaxis patients, have been received during the clinical
trials and in the post-marketing setting with this product (Refacto,
Antihaemophilic Factor) in Canada.
The lack of effect and/or low factor VIII recovery has been reported
in patients with inhibitors and also in patients who had no evidence
of inhibitors. The lack of effect has been described as bleeding
into target joints, bleeding into new joints, other bleeding or
a subjective feeling by the patient of new onset bleeding. The product
insert now reflects these observations and advises that, in view
of these reports of less than expected therapeutic effect, it is
important to individually titrate and monitor each patient's dose
of moroctocog alfa (ReFacto), particularly when initiating treatment,
to ensure an adequate therapeutic response.
Reference:
'Dear Healthcare
Professional' letter from Wyeth Canada, 30 Sept 2003. Available from
URL: http://www.hc-sc.gc.ca
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7.
ROFECOXIB / CELECOXIB
GI
adverse effects
Australia.
A significant number of cases of GI adverse effects associated with
rofecoxib and' celecoxib have been reported to the Adverse Drug
Reactions Advisory Committee (ADRAC), many involving elderly patients
with known risk factors. However,
16 reports of celecoxib-associated peptic ulcer and 16 of celecoxib-
and 5 of rofecoxib associated GI haemorrhage occurred in patients
aged less than 60 years with no stated risk factors. The Committee
points out that 'the serious events reported to ADRAC suggest that
selective COX-2 inhibitors should be treated with similar caution
to other NSAIDs'.
Reference:
Australian
Adverse Drug Reactions Bulletin 22: 15, No.4, Aug 2003.
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