Professional Documents
Culture Documents
1, 2002
EDITORIAL
REGULATORY MATTERS
ARISTOLOCHIA -- More products cancelled (Australia, Canada)................................................. 1
CAPECITABINE -- Interaction with anticoagulants (USA)........................................................... 1
DROPERIDOL -- Strengthened warning section about cardiac arrhythmias (USA)......................... 1
FLUTICASONE PROPIONATE -- New advice for prescribing (UK)................................................. 1
INFLIXIMAB -- Clinical alert: worsening congestive heart failure (Canada, Europe, USA) .............. 2
INFLIXIMAB -- Risk of infections (Worldwide).......................................................................... 2
ITRACONAZOLE -- High dose regimens may precipitate heart disorders (UK) .............................. 3
LEVONORGESTREL -- Emergency contraception to be made available
over the counter (New Zealand) .......................................................................................... 3
LIPOKINETIX -- Reports of liver injury (USA) .......................................................................... 3
KAVA – KAVA -- Piper methysticum and concerns of
liver injury (Germany, Switzerland, UK, USA) ....................................................................... 3
TOLCAPONE -- Renewal of suspension of marketing authorisation (Europe) ................................ 4
TOPIRAMATE -- Warning about ocular syndrome
(acute myopia and secondary angle closure glaucoma) (Canada, USA) .................................... 4
SAFETY OF MEDICINES
BLOOD PRODUCT INFUSIONS -- Risk of fatal acute lung injury (USA) ........................................ 5
CLOZAPINE, OLANZEPINE, QUETIAPINE, RISPERIDONE -- Atypical
antipsychotics and glucose metabolism disorders (Canada) .................................................... 5
DESOGESTREL/GESTODENE ORAL CONTRACEPTIVES -- Low risk
of venous thromboembolism (Europe).................................................................................. 5
DIGOXIN -- Increased toxicity following P-glycoprotein inhibition (Australia)............................... 6
DTaP VACCINE BOOSTERS -- Extensive limb swelling (Australia)............................................... 6
EPOETIN ALFA -- Reports of pure red blood cell aplasia (Canada, USA) ...................................... 7
GLITAZONES -- Important safety reminder (Canada, UK) ......................................................... 7
INHALED CORTICOSTEROIDS -- Use lowest effective dose in children (New Zealand) .................. 8
ISONIAZID, PYRAZINAMIDE, RIFAMPICIN -- Reports of liver disorders (Canada) ......................... 8
LAMOTRIGINE -- Dispensing errors due to name confusion (USA).............................................. 8
LEVOFLOXACIN -- Reports of adverse reactions (Belgium)........................................................ 9
LINEZOLID -- Reports of haematological disorders (UK) ........................................................... 9
MMR vaccine -- Serology tests before giving second dose if ITP occurs (UK) ............................... 9
NITROFURANTOIN -- Peripheral neuropathy (Australia)............................................................ 9
NONACOG ALFA -- Further studies for additional data (Europe) ................................................10
OPRELVEKIN -- Papilloedema in paediatric patient study (USA) ................................................10
RALOXIFENE -- Reports of thromboembolic events (Australia) .................................................10
TIAPROFENIC ACID -- Reports of cystitis (New Zealand) .........................................................11
TRADITIONAL MEDICINES – Adulterants/undeclared ingredients
pose safety concerns (New Zealand, UK) .............................................................................11
TRAMADOL -- Precipitation of serotonin syndrome (Australia) ..................................................12
FEATURE
A Reappraisal of Antipyretic and Analgesic Drugs –- Dr Anthony Wong,
MD, PhD, Medical Director, CEATOX, Instituto da Criança, Department
of Paediatrics, Faculty of Medicine, University of São Paulo, Brazil .........................................15
REGULATORY MATTERS
control, or a reduced re- data from the study to provide listeriosis and pneumocystosis
quirement for oral cortico- more definitive recommendations reported with the use of
steroids. Furthermore, only a to healthcare professionals in the infliximab. Centocor has added a
consultant physician, or a future. The above safety black box warning about these
general practitioner with information has also been opportunistic infections and
appropriate experience in the disseminated via the website of revised the Warnings and
management of asthma, the US FDA(2). The European Adverse Reactions sections in the
should initiate such a Agency for the Evaluation of product label. Centocor advises
dosage. Medicinal Products (EMEA) physicians to review the revised
reinforced the above concerns labelling for infliximab and to
Reference: through its public statements carefully assess the risks and
Current Problems in issued first in October 2001 and benefits of initiating treatment
Pharmacovigilance 27: 10, Aug
later, again in February 2002(3,4). with infliximab in patients who
2001.
have lived in endemic regions.
Reports in WHO-file: cardiac failure
INFLIXIMAB 10.
The latest EMEA Public
Statement on Infliximab issued
Clinical alert: Reference: in February 2002 also informs
1. Media Release, 23 Oct 2001.
worsening congestive health professionals about the
Available from URL: risk of infections including
heart failure http://www.hc-sc.gc.ca
tuberculosis in patients under-
2. ‘Dear Healthcare Professional’
Canada, Europe, USA. letter from Centocor, 18 Oct
going treatment with inflixmab.
Infliximab is a biological 2001. The statement advises that:
therapeutic product indicated for Available from URL: • infliximab is contraindicated
the treatment of rheumatoid http://www.fda.gov/medwatch in patients with tuberculosis
arthritis and Crohn’s disease. 3. EMEA Public Statement or other severe infections
Schering Canada and Centocor (CPMP/3257/01), 24 Oct 2001. such as sepsis, abscesses or
have issued a ‘Dear Healthcare Available from URL:
opportunistic infections;
http://www.emea.eu.int
Professional’ letter for infliximab
4. EMEA Public Statement
(Remicade) through Health • patients should be closely
(CPMP/32/02), 1 Feb 2002.
Canada’s website warning about Available from URL:
monitored for infections
the use of the drug in patients http://www.emea.eu.int including tuberculosis before,
with congestive heart failure during and after infliximab
(CHF)(1). The letter advises that (remicade) therapy, in
INFLIXIMAB accordance with local
• Infliximab therapy should recommendations;
Risk of infections
not be initiated in patients
with CHF Worldwide. In the post- • treatment with infliximab
marketing spontaneous reporting (remicade) must be
• Existing infliximab recipients for infliximab (Remicade), discontinued if the patient
with CHF should discontinue infections are the most common develops serious infections
treatment if their CHF is serious adverse event. Some of or sepsis and that before
worsening the cases have resulted in fatal starting treatment with
outcome. Up to the middle of infliximab all patients must
• Treatment discontinuation 2001, 202 deaths had been be evaluated for both active
should be considered for reported. Nearly 50% of these and inactive (latent)
existing infliximab recipients were associated with infections. tuberculosis. If active
with stable CHF and, if a Up to 31 October 2001 tuberculosis is diagnosed,
decision is made to continue approximately 130 cases of infliximab therapy must not
treatment, close monitoring active tuberculosis with extra- be initiated; if inactive
of cardiac function should be pulmonary location were (latent) tuberculosis is
undertaken. reported worldwide in patients diagnosed, prophylactic anti-
treated with infliximab tubercular therapy must be
The letter is based on the
(Remicade). A ‘Dear Healthcare started before initiating
preliminary results of an ongoing
Professional’ letter from infliximab therapy.
phase II trial assessing the use
Centocor, the Marketing
of infliximab in patients with The statement also informs
Authorisation Holder for
moderate to severe CHF which patients that while infliximab
infliximab (Remicade) was
demonstrated higher incidences (Remicade) continues to be an
posted on the US FDA’s website
of mortality and hospitalisation effective and safe medicine, it
in October 2001 detailing
for worsening heart failure in increases the risk of getting
labelling revisions for infliximab
patients treated with the higher infections, including tuberculosis.
(Remicade) about tuberculosis
dose of 10mg/kg. Centocor will Patients should inform their
(TB) and other serious infections
continue to acquire follow-up physician if they have had TB or
including histoplasmosis,
have been in close contact with a reductions in left ventricular United Kingdom, Norway and
TB patient. In addition, patients function in a recent study, the parts of Canada.
receiving infliximab should report agency reports.
Reference:
symptoms such as shortness of Media Release, 5 Oct 2001.
The agency says that while
breath, swelling in the feet etc. Available from URL:
the available evidence suggests
as these may be signs of heart http://210.48.125.104/moh.ns
that the risk of heart failure with
failure. In general, patients with
short courses of itraconazole is
a severe infection and/or
moderate or severe heart failure
low in healthy, young patients, LIPOKINETIX
prescribers should exercise
may not be treated with Reports of liver injury
caution when prescribing the
infliximab.
drug to at-risk patients. USA. The FDA has received
Amendments to the product multiple reports of persons who
Reports in WHO-file: infection
(various kinds) 46; sepsis 39
information of all itraconazole developed liver injury or liver
formulations have been made to failure while using Lipokinetix, a
Reference: reflect this information. dietary supplement (for
1. ‘Dear Healthcare Professional’
letter from Centocor, 5 Oct Reports in WHO file: promoting weight loss) marketed
2001. cardiac failure 30, cardiac failure by Syntrax Innovations Inc.
Available from URL: right 5, oedema 86, oedema Lipokinetix contains phenyl-
http://www.fda.gov/medwatch peripheral 209, oedema generalized propanolamine (PPA), caffeine,
2. EMEA Public Statement 10 yohimbine, diiodothyronine, and
(CPMP/32/02), 1 Feb 2002.
Reference: sodium usniate. The US FDA has
Available from URL: advised consumers to immedi-
Current Problems in
http://www.emea.eu.int Pharmacovigilance 27: 11-12, Aug ately stop using the product and
2001. to consult their physician if
ITRACONAZOLE experiencing symptoms of
• those with liver dysfunction demonstrated that growth suggestive of hepatitis, and to
suppression can occur with long- discontinue their regimen and
• those who are taking insulin. term exposure to such consult a physician at once if
medication. Medsafe refers to 2 such symptoms occur.
The MCA emphasises that long-term, controlled studies
Reports of liver disorders
patients who receive either drug that found that growth in associated with isoniazid,
should have their liver enzyme children receiving inhaled or pyrazinamide and rifampicin
levels monitored before initiation intranasal corticosteroids was received by the CADRMP*
of therapy, every 2 months for retarded by approximately 1cm,
the next 12 months and mainly during the first year of Anti- Total Number
periodically thereafter. Patients tubercular number of
treatment. In one of these
regimen of fatalities
whose ALT level increases to ≥ 3 studies, it was also found that
reports
times the upper limit of normal initial growth retardation was Isoniazid 258 7
should be reassessed as soon as significantly correlated with a Pyrazinamide 4 0
possible, and if this elevation younger age. The MARC advises Rifampicin 27 1
persists, treatment with the prescribers to be aware of the Isoniazid +
drugs should be terminated. cumulative effect of co- 1 1
pyrazinamide
Reports in WHO file: cardiac failure
prescribing corticosteroids with Isoniazid +
110 6
- rosiglitazone 154, pioglitazone 84; different routes of adminis- rifampicin
pulmonary oedema - rosiglitazone tration. If growth retardation Pyrazinamide
1 0
28, pioglitazone 11; hepatocellular occurs, an alternative treatment + rifampicin
damage - rosiglitazone 14, to corticosteroids should be Isoniazid +
pioglitazone 13; hepatic necrosis - considered. pyrazinamide 19 0
rosiglitazone 4, pioglitazone 5; + rifampicin
hepatitis - rosiglitazone 46, *Medsafe is New Zealand's * Canadian Adverse Drug Reaction
pioglitazone 17 Medicines and Medical Devices Monitoring Program
Safety Authority.
Reference: Reference:
1. Advisory from Health Canada, Reference: Canadian Adverse Drug Reaction
30 Nov 2001. Media Release, Sept 2001. Newsletter 11: 1, Oct 2001.
Available from URL: Available from URL:
http://www.hc-sc.ca
2. ‘Dear Healthcare Professional’
http://www.medsafe.govt.nz.
LAMOTRIGINE
letter from Eli Lilly Canada Inc.,
ISONIAZID, Dispensing errors due
6 Nov 2001.
to name confusion
Available from URL:
http://www.hc-sc.ca
PYRAZINAMIDE,
USA. The FDA has alerted
3. ‘Dear Healthcare Professional’ RIFAMPICIN pharmacists and healthcare
letter from GlaxoSmithKline, 13
Reports of liver professionals of continuing
Nov 2001.
reports of dispensing errors due
Available from URL: disorders
http://www.hc-sc.ca to name confusion involving
4. Current Problems in Canada. A number of reports of antiepileptc tablets lamotrigine
Pharmacovigilance 27: liver disorders associated with (Lamictal) and other
11, Aug 2001. the antitubercular agents medications, most commonly
rifampicin, isoniazid and pyra- Lamisil, lamivudine, Ludiomil,
INHALED zinamide have been received by
the Canadian Adverse Drug
labetolol and Lomotil.
GlaxoSmithKline has developed
CORTICO- Reaction Monitoring Program materials and suggestions for
pharmacists and physicians to
STEROIDS (CADRMP), report authors from
the Canadian Bureau of Licensed help prevent dispensing errors.
Use lowest effective Product Assessment. As at 18 The materials include a ‘shelf
dose in children May 2001, 420 reports of shouter’ for pharmacists that will
suspected liver disorders help differentiate Lamictal from
New Zealand. The New Zealand associated with these 3 anti- other stocked merchandise. A
Medicines Adverse Reactions tubercular agents had been patient-information tear sheet is
Committee (MARC) recommends received by the CADRMP (see also included to be given to
that prescribers evaluate the table). Healthcare professionals patients when prescriptions are
risks and benefits of the use of are reminded of the importance filled, facilitating communication
inhaled or intranasal cortico- of testing for liver disorders in between the dispenser and the
steroids in children, and patients receiving any anti- patients, ensuring that patients
prescribe the lowest effective tubercular regimen. The article receive the correct medication.
dose, reports Medsafe.* These also points out that it is essential
Reference:
recommendations were made in that patients are advised to 1. ‘Dear Healthcare Professional’
response to the findings of remain vigilant for the letter by GlaxoSmithKline,
recent studies, which development of any symptoms
6 Dec 2001. adverse effect of linezolid, and vaccine and ITP. Particular
Available from URL: that close weekly monitoring is attention was given to the
http://www.fda.gov/medwatch/ recommended in the following risk/benefit balance associated
safety patients: with giving a second dose of
2. ‘Dear Pharmacist’ letter by
• those who receive > 10−14 MMR vaccine to patients who
GlaxoSmithKline, Aug 2001.
Available from URL: days therapy developed ITP within 6 weeks of
http://www.fda.gov/medwatch/ their first dose of the vaccine.
safety • those with existing bone The MCA reports that, according
marrow suppression to a recently published study,
the absolute risk of developing
LEVOFLOXACIN • those who are receiving ITP after receipt of a first MMR
Reports of adverse other drugs that may vaccination is 1/22 300 cases
adversely affect (with 2/3 ITP cases attributable
reactions haemoglobin levels, platelet to MMR vaccine); this is lower
Belgium. Levofloxacin (Tavanic) function or blood counts than the risk of developing ITP
has been associated with a with wild measles (common) or
number of adverse reactions, • those with renal rubella infections (1/3000
including 12 cases of tendinitis, insufficiency. cases). The report also points
which have been reported to the The MCA advises that out that the MMR vaccine
Belgian centre for pharmaco- treatment with linezolid should product information is currently
vigilance since the drug's launch be discontinued in any patient being revised to reflect the
in August 2000. Of the 12 who develops significant bone recommendations of the CSM.
reports of levofloxacin-associated marrow suppression, unless Reports in WHO file: purpura
tendinitis, 6 cases involved continued treatment is deemed thrombocytopenic 133
tendon rupture. Also, in 5 cases, essential; in such cases, inten-
concomitant corticosteroid Reference:
sive monitoring should be
therapy may have been a Current Problems in
undertaken with appropriate Pharmacovigilance 27: 15, Aug
contributing risk factor. The management strategies im- 2001.
mean age of the patients was 74 plemented.
years, and it appears that the
risk of tendinitis with levofloxacin Reports in WHO file:
thrombocytopenia 80, anaemia 52,
NITRO-
therapy increases with age. The
centre has also received 8
leucopenia 12, granulocytopenia 7, FURANTOIN
marrow depression 9,
reports of allergic reactions with pancytopenia 16 Peripheral neuropathy
levofloxacin, including 7 of
angioneurotic oedema and 1 of Reference: Australia. The awareness of
anaphylaxis. Current Problems in nitrofurantoin-associated periph-
Pharmacovigilance 27: 14, Aug eral neuropathy, which is a well-
Reports in WHO file: tendinitis 255, 2001. established adverse effect of this
tendon disorder 268, tendon agent, may be declining, says
rupture 49, anaphylactic shock 27,
anaphylactoid reaction 102, MMR vaccine the Australian Adverse Drug
Reactions Advisory Committee
angioedema 61
Serology tests before (ADRAC). A recently published
Reference: giving second dose if case report of this complication
Folia Pharmacotherapeutica 28: 76, has prompted the committee to
Aug 2001.
ITP occurs
remind prescribers to exercise
UK. The UK CSM has caution with the use of
LINEZOLID recommended that patients who
develop idiopathic thrombo-
nitrofurantoin in the elderly,
patients with renal impairment,
Reports of cytopenic purpura (ITP) within 6 and patients who require a long
haematological weeks of receiving their first period of treatment. It adds that
disorders dose of measles, mumps and the risk of developing peripheral
rubella (MMR) vaccine undergo a neuropathy during nitrofurantoin
UK. Since its launch in the UK in serological evaluation prior to therapy may be reduced by
January 2001, 12 reports of receiving a second dose. The paying particular attention to the
haematological disorders associ- second dose is recommended use of the minimum effective
ated with linezolid (Zyvox) have where the patient is not fully dose. Additionally, prescribers
been received by the UK immune against measles, are advised that nitrofurantoin
Medicines Control Agency (MCA). mumps and rubella infections. therapy should be discontinued if
These reports have included These recommendations, which symptoms suggestive of
thrombocytopenia, anaemia, have been published on the peripheral neuropathy occur.
leucopenia and pancytopenia. website of the UK MCA, were
The MCA says that bone marrow made after the CSM reviewed all Of the 18 reports of
suppression is a recognised the available evidence on MMR nitrofurantoin-associated periph-
Centers (AAPCC) lists para- continuing pharmacovigilance in 11. Wong A, Sibbald A, Ferrero F et
cetamol as the single major older, more established drugs. al. Antipyretic effects of
cause of death reported to the dipyrone versus ibuprofen
American poison centers since versus acetaminophen in
References: children: results of a
1994(14,15). In October 2001, the
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