Medsafe also advises
that patients be warned that the initial symptoms of colchicineassociated
toxicity include nausea, vomiting and diarrhoea, and usually occur
2-12 hours after ingestion; if toxicity does occur, patients should
discontinue colchicine immediately and seek medical advice.
Reference:
Prescriber Update, December
2005, 26(2) (http://www.medsafe.govt.nz).
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2.
Glucosamine
Reports
of allergic skin reactions
Australia.
The Adverse Drug Reactions Advisory Committee (ADRAC) has received
51 reports of allergic skin reactions involving glucosamine, including
skin eruptions, pruritus, urticaria and angioedema. According
to ADRAC, Australian labels on products that contain glucosamine
specify whether it is sourced from seafood. ADRAC warns that people
who have a shellfish allergy may be more susceptible to allergic
skin reactions if they ingest glucosamine obtained from seafood.
Patients tolerated other glucosamine-containing product without
adverse reactions in several cases reported to ADRAC.
Reference: 
Australian Adverse Drug Reactions
Bulletin, December 2005, 24(6):23.
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3.
Glucosamine products
86
reports to date in Sweden
Sweden.
The Swedish Adverse Drug Reactions Database contains 86 reports
of suspected adverse reactions associated with glucosamine products
from 2001 until February 2006, according to the Swedish Medical
Products Agency. The Agency says that the majority of these cases
were reported after 2002, when the first glucosamine product,
Artrox, was approved as a drug. According to the Agency, there
are now just over 10 glucosamine products approved in Sweden,
including Artrox, Glucosine, Glukosamin Copyfarm and Glukosamin
Pharma. According to the Agency, previously unknown adverse reactions
of particular interest included the following: angioedema (n =
2), urticaria (1), colitis (2), gastric/duodenal ulcer (3), oedema/lower
limb oedema (3), dizziness (4), arthralgia (2), bronchial asthma/bronchial
asthma aggravated (3), diabetes aggravated (2) and hypercholesterolaemia
(2). There were also three cases of an increased effect of warfarin
during concomitant treatment with glucosamine products.
(Reports in WHO database: All
reactions - 645).
Reference:
Three year adverse reaction
follow-up of glucosamine products as drugs. Swedish Medical Products
Agency, 21 April 2006 (http://www.moa.se).
------------------------------------------------------------------------------------------------
4.
Colchicine
Toxic
in overdose: reminder
New
Zealand. Prescribers
are reminded of the revised dosage advice for colchicine because
of the risk of serious dose-related adverse effects, in a recent
Prescriber Update article. New
Zealand's Medsafe Pharmacovigilance
Team reminds prescribers that colchicine is now indicated as second-line
therapy for acute gout. The team warns that colchicine is extremely
toxic in overdose, and that fatalities have occurred. They say
that the use of high doses in acute gout is not appropriate, especially
in patients who are elderly, have impaired renal or hepatic function,
or weigh less than 50
kg. According to Medsafe, in otherwise healthy
adults, the maximum colchicine dose is 2.5 mg in the first 24
hours and the total dose should not exceed 6 mg over four days
in an acute attack' the dosing interval has been' increased to
every six hours instead of every two to three hours. In addition
the team advises that continued dosing until adverse gastrointestinal
events occur "is no longer considered safe or appropriate".
Medsafe urges prescribers to write clear dosage advice on the
prescription, inform patients of the revised dosage advice, stress
how important it is not to exceed the maximum doses, warn patients
of colchicine toxicity symptoms and advise them to immediately
stop the drug and see a doctor if symptoms occur.
Reference:
Prescriber Update, June 2006,
27(1): 2
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5.
Ibuprofen
Interaction
with low-dose, non-coated aspirin
USA.
The US FDA has warned health-care providers that ibuprofen can
interfere with the anti-platelet effect of low dose aspirin (81
mg per day), potentially rendering aspirin less effective when
used for cardioprotection and stroke prevention. It has been demonstrated
in published and unpublished human ex vivo studies, that ibuprofen
interferes with the anti platelet activity of low dose aspirin
(81 mg, immediate release) when they are ingested concurrently.
The mechanism by which this occurs may be through competitive
inhibition of the acetylation site of cyclooxygenase (COX) in
the platelet. Both ibuprofen (reversible inhibition) and aspirin
(irreversible inhibition) occupy nearby sites on COX, such that
the presence of ibuprofen interferes with aspirin binding. Once
the ibuprofen releases from the binding site, COX will not be
inhibited because some aspirin available to bind will have been
excreted. This ibuprofen interference attenuates the expected
aspirin-mediated irreversible inhibition of thromboxane B2 (TXB2)
production and the expected inhibition of platelet aggregation.
Health-care professionals should advise consumers and patients
regarding the appropriate concomitant use of ibuprofen and aspirin.
They should consider:
- counselling
patients about the appropriate timing of ibuprofen dosing if
they are also taking aspirin for cardioprotective effects.
- with occasional
use of ibuprofen, there is likely to be minimal risk from any
attenuation of the antiplatelet effect of low dose aspirin,
because of the long-lasting effect of aspirin on platelets.
- patients
who use immediate release aspirin (not enteric coated) and take
a single dose of ibuprofen 400 mg should dose the ibuprofen
at least 30 minutes or longer after aspirin ingestion, or more
than 8 hours before aspirin ingestion to avoid attenuation of
aspirin's effect.
- recommendations
about the timing of concomitant use of ibuprofen and entericcoated
low dose aspirin cannot be made based upon available data.
- other
nonselective OTC NSAIDs should be viewed as having the potential
to interfere with the anti platelet effect of lowdose aspirin
unless proven otherwise.
- prescribing
analgesics that do not interfere with the antiplatelet effect
of low dose aspirin for high risk populations.
Reference:
Healthcare Professional Sheet.
United States Food and Drug Administration, 8 September 2006 (http://www.fda.gov).
---------------------------------------------------------------------------------------------
6. Counterfeit medicines: an intent to deceive
Valerio Reggi, IMPACT, WHO
It has been said that imitation is the highest form of flattery. However, we can do without this type L. flattery if it harms our health. 'Brand name' goods such as watches and clothes have always attracted the attention of unscrupulous counterfeiters everywhere in the world. Unfortunately, this menace has also spread to the world of medicines,
putting hundreds and thousands of unsuspecting
lives into serious danger. Counterfeiting is deceptive and immoral in any field.
But in healthcare, it is criminal and simply unacceptable.
What
are counterfeit medicines?
According to WHO, a counterfeit medicine is a product which is 'deliberately and fraudulently mislabelled with respect to identity and/or source'. Counterfeiting can apply to both branded and generic products and counterfeit products may include products with the correct ingredients or with the wrong
ingredients, without active ingredients, with insufficient active ingredients or with fake packaging. It is important
to make a distinction between
counterfeit medicines and other kinds of substandard medicines: all counterfeit medicines
are substandard because they are manufactured and distributed outside of regulatory control and their composition is unpredictable. On the other hand, not all substandard medicines are counterfeit because not all of them have been 'deliberately and fraudulently mislabelled'. Experience has shown that there are 'many kinds' of counterfeit medicines. Counterfeiters have targeted well known as well as unbranded products, expensive as well as inexpensive products. They have even produced fake medicines that do not refer to any existing brand or manufacturer.
What
are the consequences of
counterfeit medicines?
Therapeutic failures and adverse effects would be the more serious consequences. In fact many cases of counterfeiting have been uncovered while investigating therapeutic failure or adverse events observed in patients. But a serious if not fatal consequence is the erosion of confidence in health-care systems.
Where
do we find counterfeit medicines?
Everywhere. No country is outside the counterfeiters' reach, the problem is truly global. Counterfeit medicines are increasingly detected in European and North-American countries. This suggests that even countries with advanced regulatory systems are seriously challenged by this menace. Nor are some medicines free from this disgrace; if widely used medicines such as atorvastatin and paracetamol are counterfeited, so are other, less commonly used products such as growth hormone, paclitaxel and filgastrim. Stated differently, counterfeits can
surface in community pharmacies and in hospitals alike.
Nobody knows the precise extent of the problem. Counterfeits are difficult to detect, investigate or quantify. Rough estimates, mainly based on unpublished reports, suggest that up to 10% of the medicines circulating in the world could be counterfeit. It is very likely that this estimate is not a realistic description of the situation of the best regulated countries of the world.
Yet, even a few dozen cases in a year mean many thousands of tablets and ampoules and
therefore many thousands of patients at risk!
Who
are the counterfeiters?
Counterfeiting medicines has attracted organized crime, but it also requires the cooperation of people with some experience in pharmaceutical manufacturing and distribution. In addition to organized crime, there are small-scale counterfeiting activities. And individuals indulge in it as well, as in the case of Robert Courtney, a Kansas City pharmacist who, in ten years, accumulated at least
US$19 million by diluting injections, often prepared for patients he personally knew. He got a 30-year prison sentence.
Counterfeiting is 'easy business' because:
- it is relatively easy to hide and smuggle medicines: very few countries have customs control that is
specialized in detecting counterfeit medicines;
- most users are not able to distinguish between real and counterfeit;
- manufacturing bad quality medicines does not require huge investment and the equipment is easy to move from one 'counterfeit' site to another;
- in many countries, regulatory and control systems, especially oversight on distribution channels, are ineffective;
- in addition, in most countries, punishment is not sufficiently strong to deter criminals.
And governments face considerable challenges in fighting the menace because of:
- a
lack
of Willingness to recognize the
existence or the seriousness of the problem;
- inadequate
legal framework and
ineffective punishment: counterfeiting medicines is not properly defined and is dealt with in the same way as all other types of counterfeiting;
- weak administrative and coordination measures;
- ineffective control on pharmaceutical manufacturing, importation and, especially, distribution.
Additional factors include national drug policies that prioritize export activities over compliance with good manufacturing practices; ineffective collaboration among
authorities and institutions involved in regulation, control, investigation and prosecution (e.g. Drug regulatory authorities, police, customs and the judiciary); an extremely fragmented distribution channel that increases the opportunities for counterfeiters to infiltrate the system; wide price gaps or extremely high prices in countries that cause patients to 'wander' in search of 'affordable' versions of the medicines; internet vending of medicines; and third-party manufacturing, which, if not properly and carefully organized, may lead to unauthorized and substandard use of manufacturing techniques and packaging materials.
How
to protect public health?
Combating counterfeit medicines requires collaboration, at national, regional and international levels involving all stakeholders of the public sector and the civil society including health
professionals, patients, manufacturers, distributors, as well as communication professionals and the media. But the first step is to sensitize and obtain the commitment of law-makers to introduce adequate legislative measures that clearly define and recognize counterfeiting of medicines as a crime that is different
and far more serious than the counterfeiting of other kinds of goods.
Efficient coordination mechanisms
should be put in place for rapid and effective anti-counterfeit measures without bureaucratic delay. While regulations and controls should not unnecessarily hinder the exportation of medicines, it is necessary to ensure that both exporting and importing countries can apply measures that permit to effectively identify the actual origin of exported medicines. Liberalization and intensification of international trade offer opportunities for trading in medicines
of unclear origin, including counterfeits. It is necessary that national authorities improve border control and develop appropriate international collaboration and exchange of information through international
legal and administrative agreements. Essential stakeholders in these efforts should include Interpol, the Organisation for Economic Co-operation and Development, the World Customs Organization, the World Intellectual Property Organization, the World Trade Organization, and the World Health Organization.
Pharmaceutical manufacturers and their associations are also key players in combating counterfeit medicines. In the past, many companies kept quiet on the cases that were detected, probably fearing negative publicity for the company products. However, this attitude has now changed. Industry has an important role in providing information as well as in developing technologies that help detect and deter the manufacture of counterfeit medicines. In a similar vein, distributors, wholesalers, importers and exporters should develop and effectively implement business practices that make the distribution chain impermeable to counterfeits and open to appropriate verification by national authorities. Purchasing organizations and NGOs should similarly develop appropriate procurement procedures. Other players in this important battle are the health professionals; nurses and pharmacists should stay vigilant to the presence of counterfeits and report suspicious products. Similarly, physicians should
rule out counterfeits as a possible cause of adverse reactions or therapeutic failure. To complete the cycle of protection, the public must do their bit as well: patients must report to their pharmacists and doctors if they sense any irregularity with their medication, if they experience a side effect or a decrease in beneficial effect.
The International Medical Product Anti-Counterfeiting Taskforce, IMPACT was established by WHO with the aim of bringing together all key stakeholders at the international, regional and national level, to effectively combat counterfeit medicines. The Declaration of Rome, included on the next page describes the background and captures the remit of the task force.
DECLARATION OF ROME
18
FEB 2006
The participants of the WHO International Conference 'Combating Counterfeit Drugs: Building
Effective International Collaboration', gathered in Rome on 18 February 2006
- Counterfeiting
medicines, including the entire range of activities from manufacturing
to providing them to patients, is a vile and serious criminal
offence that puts human lives at risk and undermines the credibility
of health systems.
- Because
of its direct impact on health, counterfeiting medicines should
be combated and punished accordingly.
- Combating
counterfeit medicines requires the coordinated effort of all
the different public and private stakeholders that are affected
and are competent for addressing the different aspects of the
problem.
- Counterfeiting
medicines is widespread and has escalated to such an extent
that effective coordination and cooperation at the international
level are necessary for regional and national strategies to
be more effective.
- National,
regional and international strategies aimed at combating counterfeit
medicines should be based on:
a)
political will, adequate legal
framework, and implementation commensurate to the impact of this
type of counterfeiting on public health and providing the necessary
tools for a coordinated and effective law enforcement,
b)
inter-sectoral coordination
based on written procedures, clearly defined roles, adequate resources,
and effective administrative and operational tools,
c)
creating an awareness about
the severity of the problem among all stakeholders and providing
information to all levels of the health system and the public,
d)
development of technical competence
and skills in all required areas,
e)
appropriate mechanisms for
ensuring vigilance and input from healthcare professionals and
the public.
- The WHO
should lead the establishment of an International Medical Products
Anti-Counterfeiting Taskforce (IMPACT) of governmental, non-governmental
and international institutions aimed at:
a)
raising awareness among international
organizations and other stakeholders at the international level
in order to improve cooperation in combating counterfeit medicines,
taking into account its global dimensions
b)
raising awareness among national
authorities and decision-makers and calling for effective legislative
measures in order to combat counterfeit medicines
c)
establishing effective exchange
of information and providing assistance on specific issues that
concern combating counterfeit medicines
d)
developing technical and administrative
tools to support the establishment or strengthening of international,
regional and national strategies
e)
encouraging coordination among
different anti-counterfeiting initiatives.
The IMPACT shall function on
the basis of existing structures/institutions and will in the
long term explore further mechanisms, including an international
convention, for strengthening international action against counterfeit
medicines.
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7.
Non-selective non-steroidal anti-inflammatory drugs (NSAIDs)
Review
completed; overall benefit-risk favourable
Europe.
The Committee for Medicinal Products for Human Use (CHMP) at the
European Medicines Agency (EMEA) has concluded that the benefit-risk
balance for non-selective NSAIDs remains favourable. This conclusion
was based on a review announced in September 2006 of new thrombotic
cardiovascular safety data. An EMEA Press Release states that
non-selective NSAIDs:
