The
Pharmaceutical Journal Vol 266 No 7131 p71-74
The combined measles, mumps and rubella (MMR) vaccine remains the safest way
to protect children against these diseases, according to the Committee on Safety
of Medicines and the Joint Committee on Vaccination and Immunisation.
At a press briefing held at the Department of Health on January 12, Professor
Alasdair Breckenridge (chairman, CSM) said that there was a “large body of evidence”
to support the long-term safety of the MMR vaccine. However, there was a lack
of quality safety data for the single component measles, mumps and rubella vaccines.
Commenting on concerns about the MMR vaccine’s proposed relationship with autism
and inflammatory bowel disease, he said that four recent specific studies had
shown no link.
Professor Michael Langman (chairman, JCVI), also speaking at the press briefing,
said that children were currently at risk from preventable diseases, such as
measles. Recent measles outbreaks in unvaccinated populations in Ireland and
the Netherlands had led to deaths. In Japan, where single component vaccines
had been used, rather than the combined MMR vaccine, 79 deaths from measles
had been reported between 1992 and 1997. No deaths from measles had been reported
in the United Kingdom since 1990, he said.
Dr David Salisbury (head of immunisation, Department of Health) commented that
the uptake for MMR vaccination had fallen from around 92 per cent in 1995-96
to around 88 per cent at present. However, there were indications that the uptake
might be increasing again. The Department’s own market research among young
mothers showed that confidence in the MMR vaccine was rising as a result of
the meningitis C vaccination campaign. It would be unfortunate if that confidence
was undermined by unfounded stories, he said.
The DoH says that much of the press reporting has been based on a study by Dr
Andrew Wakefield (Royal Free Hospital, London) which is expected to be published
shortly. (Dr Wakefield and colleagues first suggested a causal link between
the MMR vaccine and autism or inflammatory bowel disease in a study published
in the Lancet in 1998 [PJ, March 7, 1998, p329].) The CSM has
performed a detailed review of all the evidence relating to the safety of MMR
vaccine and has advised the Government that giving it is safer than giving the
components separately.
During the press briefing, Professor Langman made reference to a 14-year follow-up
study of 1.8 million individuals immunised with MMR vaccine in Finland. In this
study, Dr Annamari Patja (Helsinki university central hospital, Finland) found
that 173 potentially serious reactions that were reported to be vaccine-related
resulted from the three million doses administered by the end of 1996 (Pediatric
Infectious Diseases 2000;19:1127). The researchers say that 45 per cent
of these events were probably caused by some other factor and that serious events
causally related to MMR vaccine are rare and greatly outweighed by the risks
of acquiring the infections naturally.
The researchers also comment that no cases of inflammatory bowel disease or
autism were detected during the study. They say that this finding was important
because if there was “an association with MMR vaccination after such a short
interval as suggested, this prospective study design would undoubtedly have
disclosed at least some cases”.
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Many health professionals have reservations about giving children the second
dose of measles, mumps and rubella (MMR) vaccine, according to research carried
out in North Wales. Furthermore, the wide variation in knowledge and practice
regarding MMR vaccination may be influencing advice given to parents (British
Medical Journal 2001;322:82).
Dr Marko Petrovic (department of public health, North Wales health authority)
and colleagues questioned 140 health visitors, 204 practice nurses and 165 general
practitioners in North Wales about their views on MMR vaccination. Of those
who said they gave advice on immunisation to parents, nearly half had reservations
about the second dose of the vaccine and 3 per cent disagreed with the policy
of giving it.
The researchers found that nearly a fifth of the GPs had not read the MMR section
in the “green book” (Immunisation Against Infectious Disease) and that 29 per
cent said that they had not received the Health Education Authority’s factsheet
on MMR immunisation.
They comment that about a third of practice nurses believed that autism and
Crohn’s disease might be linked to MMR vaccination, despite expert advice to
the contrary. In addition, 80 per cent of all the health professionals questioned
were not aware of the documented association between the vaccine and idiopathic
thrombocytopenic purpura. Dr Petrovic et al conclude that many health
professionals do not know about, or use, nationally available resources on immunisation.
In response to the study, the Department of Health said on January 11: “It is
important for health professionals to keep up to date with all the available
scientific literature, and this study shows that those health professionals
who were more informed were more confident about the vaccine”.
Professor Martin Kendall (chairman, British National Formulary joint formulary
committee) said in a press release issued on January 11: “This study effectively
highlights the shortcomings of the current methods of disseminating important
information. Prescribers and other health care professionals need easy access
to up-to-date and reliable information on medicines, including vaccines.”
The DoH is currently producing an updated factsheet on MMR for health professionals
and a new leaflet for parents. More information is available on the Department’s
website (www.immunisation.org.uk).
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Training material on emergency hormonal contraception (EHC) is enclosed with
this week’s Pharmaceutical Journal. A Centre for Pharmacy Postgraduate
Education (CPPE) booklet provides full information about pharmacy supply of
EHC, and a practice checklist, produced by The Journal and the CPPE,
serves as a reminder of the key points.
The CPPE booklet contains information on the clinical aspects of emergency contraception
and advice on how to deal with requests for emergency contraception.
The booklet includes specific advice for potential contraceptive pill failures.
It says that failure of the combined pill can occur after two or more pills
are missed from the first seven pills of a packet, or four or more pills are
missed mid-packet. If two or more pills are missed from the last seven pills
of a packet, EHC is not required, provided the woman misses the pill-free break
and starts taking her next packet immediately after finishing the current one.
For progestogen-only pills, failure can occur if one or more pills is missed
or taken more than three hours late.
Advice that should be given to women when supplying EHC is covered. The main
points are:
One concern that pharmacists have, and that the CPPE booklet highlights, is
that women may request EHC repeatedly. The booklet says that EHC should not
be used as a regular contraceptive but there is no reason for supply to be refused
simply because it is a repeat request. It points out that there is no evidence
to suggest that women would use EHC as regular contraception.
Fears over the pharmacist’s legal liability regarding EHC supply are also discussed.
The booklet uses the example of supplying EHC to a woman who is already pregnant
but gives false information. The booklet states that there is no evidence to
suggest that EHC would harm an unborn child. In terms of liability, it suggests
that pharmacists should ensure that they can demonstrate that their pharmacy
has appropriate systems in place, such as a written checklist of information
to obtain before supplying EHC. The booklet also contains an action plan to
help with preparations for the supply of EHC.
Meanwhile, the CPPE says that it is responding to vigorous demand for places
on its EHC training workshops. Dr Peter Wilson (director, CPPE) told The
Journal on January 16 that it is the first time that demand has been so
high. Places on the initial 100 workshops were filled, so a further 70 workshops
were added and 20 more are currently in preparation. He said that the CPPE would
be writing to everyone on a waiting list for a place once a date became available.
All workshops would take place by the end of March, he added.
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Caffeine ingestion may increase the risk of first-trimester spontaneous abortion
among non-smoking women, according to Swedish researchers.
Dr Sven Cnattingius (Karolinska institute, Stockholm, Sweden) and colleagues
assessed the risk of caffeine intake during pregnancy in 562 women who had had
a spontaneous abortion during their first trimester and in 953 matched controls.
The researchers found that, among non-smokers, the risk of an early spontaneous
abortion doubled with a caffeine intake of 500mg or more per day. The increase
in risk was related to the amount ingested. However, among smokers, ingesting
caffeine was not found to be associated with an excess risk. The authors say
that smoking increases the rate at which caffeine is eliminated and the effect
of maternal smoking may conceal an effect of caffeine on the risk of spontaneous
abortion. They add that caffeine is metabolised more slowly in pregnant women
than in non-pregnant women and reducing caffeine intake during early pregnancy
might be prudent (New England Journal of Medicine 2001;343:1839).
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Pharmacists in rural areas should advise pregnant women to avoid close contact with sheep during lambing periods, as it may risk the health of their unborn child. The National Assembly for Wales’s departments of health and agriculture, which issued the warning, say that, although the number of reports of infection from contact with sheep is extremely small, it is important that pregnant women are aware of the risks.
Droperidol (Droleptan) products will be discontinued from March 31, and will
not be available in pharmacies shortly after this date, the Committee on Safety
of Medicines (CSM) has announced.
In a statement issued on January 10, the CSM says that the action was taken
voluntarily by Janssen-Cilag (the United Kingdom manufacturer of Droleptan)
following a risk-benefit assessment requested by the Medicines Control Agency.
The assessment had raised concerns about the potential effect of droperidol
on the cardiac QT interval.
Prescribers are advised by the CSM that droperidol can continue to be used for
its licensed acute use (to calm manic, agitated patients) while supplies are
available, but that no new patients should be given the drug for chronic use.
In addition, the CSM says that treatment with droperidol should not be stopped
until a suitable alternative has been identified.
Existing patients currently receiving droperidol as a chronic therapy should
be recalled for review by their psychiatrist and switched to an alternative
treatment. The CSM advises that chronic droperidol therapy should be reduced
over a period of one or two weeks while replacement antipsychotic therapy is
initiated.
Janssen-Cilag has written to health care professionals informing them of the
product’s discontinuation. The company says that the oral formulations of droperidol
will be discontinued to prevent their use in chronic conditions and that the
injectable form will no longer be commercially viable. Droperidol is currently
indicated for tranquillisation and emergency control in mania. The injection
is also indicated for the treatment of cancer chemotherapy-induced nausea and
vomiting, postoperative nausea and vomiting, and for use in anaesthesia as premedication.
Dr David Taylor (chief pharmacist, Maudsley hospital, London) told The Journal
on January 16 that the discontinuation of droperidol was entirely justified.
He said that the move was in line with recent restrictions on the use of thioridazine
(PJ, December 16, 2000, p877)
and the withdrawal of cisapride (PJ, July 29, 2000, p152)
and had come about because companies recognised the dangers of using drugs that
prolonged the QT interval.
Commenting on alternative treatments for acute control of mania, he said that
haloperidol was probably droperidol’s closest relative and could be used. However,
it had important differences - it was not as sedative as droperidol, it had
a longer duration of action and it also prolonged the QT interval (although
the extent to which it did this was not known). Dr Taylor added that intramuscular
formulations of atypical antipsychotic drugs would soon be available and would
increase treatment options. In addition, the more rigorous licensing process
that was in place now meant that newer drugs had much clearer risk-benefit profiles.
Further information on the discontinuation of droperidol can be obtained from
Janssen-Cilag’s medical information department (tel 0800 731 8450) or the MCA
central inquiry point (tel 020 7273 0000, e-mail info@mca.gov.uk).
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Researchers in the United States have called for more effective ways of communicating
drug safety data, after finding that action taken by the Food and Drug Administration
(FDA) in 1998 had “no material effect” on the prescribing of cisapride.
Dr Walter Smalley (Vanderbilt university school of medicine, Nashville, Tennessee)
and colleagues studied the prevalence of inappropriate use of cisapride in three
sites, both before and after the FDA had issued a warning to health care professionals
to say that the drug was contraindicated in patients at risk of cardiac arrhythmias.
In the year before the FDA took action, the proportion of patients prescribed
cisapride in the three sites, despite having a condition or taking concomitant
medication that contraindicated its use, was 26, 30 and 60 per cent. In the
year after, these figures were 24, 28 and 58 per cent, respectively, which the
authors say equates to a reduction of about two patients per 100 cisapride users
at each site.
“The exposure of these patients to inappropriate cisapride use, despite the
prominent publication of case reports, label changes and Dear Health Care Professional
letters, highlights the need to develop more effective methods for modifying
practice to reflect new information about a drug’s risks and benefits,” the
researchers say.
The medicines most commonly given to patients inappropriately at the same time
as cisapride were amitriptyline, erythromycin and clarithromycin. The most common
conditions in which contraindicated use of cisapride occurred were heart failure
and other ischaemic heart disease.
The total number of cisapride users at the three sites before the FDA’s action
was 24,840 and there were 22,459 users afterwards (Journal of the American
Medical Association 2000;284:3036). Cisapride products were discontinued
in both the US and the United Kingdom in July, 2000 (see PJ, July 29,
2000, p152).
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Selective cyclo-oxygenase 2 (COX-2) inhibitors may be appropriate for patients
with asthma and aspirin intolerance, according to researchers.
Dr Barbro Dahlén (Karolinska hospital, Stockholm, Sweden) and colleagues gave
increasing doses of celecoxib (Celebrex) to 27 patients with stable, chronic
asthma in whom aspirin had caused a drop in forced expiratory volume in one
second of 20 per cent or more.
The authors say that patients given a 200mg dose of celecoxib did not suffer
bronchoconstriction or extrapulmonary reactions. However, they add that, until
larger, long-term studies confirm this finding, patients with asthma and aspirin
intolerance should only be given selective COX-2 inhibitors under research conditions.
In a letter to the New England Journal of Medicine (2001;344:142), they
speculate that inhibition of COX-1 is the likely link between bronchospasm and
ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). The summary of
product characteristics for celecoxib states that the drug is contraindicated
in patients who have experienced asthma after taking aspirin or NSAIDs.
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Trizivir, a preparation combining three antiretroviral agents in one tablet,
was launched by Glaxo Smithkline this week. Each tablet contains abacavir, lamivudine
and zidovudine and is suitable for adults with HIV starting treatment or those
for whom adherence is a problem.
However, the company recommends that, because of potential hypersensitivity
reactions to abacavir (PJ, August 19, p259),
the individual components should be given separately for the first six to eight
weeks of treatment. In clinical trials, approximately 4 per cent of subjects
receiving abacavir developed hypersensitivity reactions, some of which were
fatal. In patients diagnosed with a hypersensitivity reaction, treatment with
abacavir must be discontinued immediately and never restarted, says the company.
At the product’s launch on January 16, Dr Emanuel Vlahakis (HIV medical adviser,
Glaxo Smithkline) said that one advantage of the new formulation was that it
allowed patients to take only two tablets a day. He also commented that the
cost of 30 days’ supply of Trizivir was equivalent to the total cost of the
individual components (see p94).
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Elan Pharma has launched a lozenge containing fentanyl citrate for the treatment
of breakthrough pain in patients who are already receiving opiates for chronic
pain. The lozenge, called Actiq, is mounted on a handle and is intended to be
sucked to maximise the amount of drug that crosses the buccal mucosa (see p94).
In a press release issued on January 15, Elan Pharma said that Actiq provided
rapid pain relief and had demonstrated superior pain relief to immediate release
morphine, the usual treatment used for breakthrough pain in the United Kingdom.
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The Cystic Fibrosis Trust is piloting a scheme to provide information about
the disease through computer kiosks in hospitals.
Patients will be able to access information about all aspects of cystic fibrosis
by touching a computer screen, according to the trust and topics of interest
can be printed out. The scheme, sponsored by Pathogenesis, is to be piloted
at six hospitals in the United Kingdom. They are: Southampton General hospital,
London Chest hospital, Great Ormond Street hospital, Frimley Park hospital,
Nottingham City hospital and the Royal Manchester children’s hospital.
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Further evidence supporting the health benefits of reducing salt intake
is provided by a new study. The results indicate that a low sodium intake,
particularly in combination with a diet high in fruit, vegetables and
low-fat dairy produce, lowers blood pressure. |
 Study confirms that low salt intake reduces blood pressure |
The United States Food and Drug Administration has declined to approve gemifloxacin
mesylate (Factive), a quinolone antibiotic that was under review for the treatment
of respiratory tract infections. The manufacturer of the product is Glaxo Smithkline.
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The December, 2000, issue of the Drug and Therapeutics Bulletin includes
a review of cytochrome P450 enzymes and their effect on drug metabolism. The
review includes a discussion of how various polymorphisms of the enzymes can
affect the efficacy of drugs, which may explain why some individuals have either
poor or exaggerated responses to certain drugs (2000;38:93).
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The first two women have been recruited for a British trial of a vaccine against
cervical cancer.
Ultimately, 24 women who have had abnormal cervical smears will be given different
doses of the vaccine, which boosts the immune response against human papilloma
virus. The trial is being carried out at St Mary’s hospital in Manchester. Results
are expected in 2002 but it is likely to be 10 years before a vaccine becomes
widely available, according to the Imperial Cancer Research Fund and the Cancer
Research Campaign which are funding the trial.
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A vaccine that provides active immunisation against meningococcal meningitis
serogroups A, C, W135 and Y has been launched by Smithkline Beecham
(now Glaxo Smithkline).
The vaccine, ACWY Vax, is recommended for subjects at risk of meningitis, such
as those living in or travelling to areas where the disease is epidemic or highly
endemic (see p94).
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Smithkline Beecham (now Glaxo Smithkline) has ended clinical investigation
of lotrafiban because of concerns over the drug’s efficacy and safety. The company
said recently that a phase III trial had been under way to test the efficacy
of lotrafiban in preventing recurrent strokes and heart attacks. However, an
independent data and safety monitoring board had recommended that the trial
be stopped.
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The World Health Organisation (WHO) has issued a warning to holidaymakers to
take all possible precautions against malaria. The organisation has acted after
receiving “numerous” reports recently of travellers, particularly to Africa,
returning home with the disease.
“Travellers often have the misconception that if they travel to malaria areas
for very short periods of time, they do not need to worry about malaria prophylaxis,”
said Dr David Heymann (executive director for communicable diseases, WHO). However,
it was possible to receive just one bite that would inoculate the malaria parasites,
he added.
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