The
Pharmaceutical Journal Vol 266 No 7130 p43-45
Positive results reported
for GP-pharmacist collaboration
Study shows coronary benefits of HRT
Second rabies vaccine available in the UK
“No justification” for renal dose dopamine in critically ill patients
Overdiagnosis of asthma linked with obesity?
First once-weekly treatment for osteoporosis launched
Study results reveal true cost of hip fracture
Clinical studies begin on oral contraceptive for men
Lisinopril for migraine prophylaxis?
US warning of lactic acidosis with HIV drugs
Capecitabine-docetaxol combination may improve breast cancer survival
Pharmacists and general practitioners (GPs) can work together to deliver improved
care for patients with angina, research suggests. A specified model of care
was delivered by five community pharmacists, through pharmacist-run clinics,
to 208 patients with stable ischaemic heart disease at eight general practices,
in a five-month study conducted by researchers from the University of Manchester.
The model of care was based on smoking cessation, dietary advice, exercise,
and treatment with aspirin, beta-blockers or statins.
Patients were reviewed by the pharmacists, who developed individualised care
plans and referred patients to GPs for investigations or medication review (with
recommendations relating to angina medication made by the pharmacist). The views
of GPs and pharmacists following the study were recorded.
Most of the therapeutic interventions suggested by pharmacists to GPs were accepted
and implemented. This, the authors say, illustrates a dependent prescribing
role for pharmacists within the confines of the study protocol. The study had
a positive impact on the relationship between GPs and pharmacists. There was
a high level of confidence in, and acceptance of, community pharmacists in the
management of patients with ischaemic heart disease among the GPs.
Most of the pharmacists reported a closer, more constructive relationship with
the GPs, many of whom wanted to continue working with the pharmacists.
One GP commented: “There is no doubt that he [the pharmacist] could become a
member of the team here. There is obviously a lot more work we can do together
. . . [in] big areas like gastrointestinal disease. . . . I could see him interviewing
these patients, getting their prescriptions sorted out, telling them what their
drugs are for, perhaps even converting them to cheaper therapy.” All participating
pharmacists were comfortable with the prospect of extending their role into
more direct patient management.
The study is published in the International Journal of Pharmacy Practice
(2000;8:275).
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Results from a new study support the hypothesis that hormone replacement therapy
(HRT) may be associated with coronary benefits.
In an analysis of data from the Nurses’ Health Study, female nurses with no
history of heart disease who used HRT after the menopause were found to have
fewer maj-or coronary events. However, the risk for stroke appeared to increase
with HRT use.
Dr Francine Grodstein (Harvard medical school, Boston, United States) and colleagues
followed 70,533 nurses for up to 20 years, between 1976 and 1996, and identified
1,258 major coronary events (non-fatal myocardial infarction or fatal coronary
disease) and 767 strokes. When all cardiovascular risk factors were considered,
the risk for major coronary events was lower among current users of HRT, including
short-term users, than in women who had never used HRT (relative risk, 0.61
[95 per cent confidence interval, 0.52-0.71]). Duration of hormone use had little
influence on the observed inverse association.
In contrast to this, women taking 0.625mg or more of oral conjugated estrogen
daily had a significantly increased risk of stroke (relative risk, 1.35 [1.08-1.68]
for doses of 0.625mg/day and 1.63 [1.18-2.26] for doses of 1.25mg/day or more).
Women taking estrogen plus progestin had a relative risk for stroke of 1.45
(1.10-1.92).
Overall, the risk for combined cardiovascular disease (major coronary heart
disease plus stroke) was lower among women taking estrogen than for women who
had never used HRT (relative risk, 0.57 [0.39-0.83] for 0.3mg estrogen daily,
0.81 [0.70-0.95] for 0.625mg/day and 0.95 [0.76-1.20] for 1.25mg/day or more).
However, the researchers found little relationship between current use of combination
HRT and combined cardiovascular disease.
The researchers comment that women must make informed decisions about their
hormone use and should consider alternatives to healthy ageing that pose no
risks, such as physical activity, a healthy diet and smoking cessation (Annals
of Internal Medicine 2000;133:933).
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Rabipur, a vaccine for the prophylaxis and treatment of rabies, is now available
in the United Kingdom. The vaccine will be distributed through MASTA (Medical
Advisory Services for Travellers Abroad) (net price, £22.15 for one dose).
Rabipur provides effective protection from day 14, with 100 per cent seroconversion
by day 28, for up to five years. The summary of product characteristics for
the vaccine says that for pre-exposure prophylaxis, reinforcing doses are generally
required every two to five years.
In comparison, the summary of product characteristics for Aventis Pasteur MSD’s
human diploid cell rabies vaccine (HDCV) says that a single reinforcing dose
should be given at two or three year intervals to those at continued risk. Aventis
Pasteur told The Journal on January 9 that both vaccines were highly
immunogenic and that the risk of local and systemic reactions were the same
for both.
Type III hypersensitivity reactions had been reported with HDCV in the United
States after booster doses and were attributed to a component of the vaccine,
beta-propiolactone. Beta-propiolactone is also present in Rabipur.
A spokesman for MASTA said that Rabipur, which was cultivated in purified chick
embryo cells, was subjected to a repeated purification process which reduced
the risk of allergenic response to the vaccine.
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Low-dose dopamine does not protect critically ill patients from renal dysfunction,
according to researchers from Australia and New Zealand.
The researchers, members of the ANZICS (Australian and New Zealand Intensive
Care Society) clinical trials group, say that physicians commonly use low-dose
dopamine in critically ill patients because, in healthy volunteers, it increases
renal blood flow and induces natriuresis and diuresis.
In a randomised trial, 324 patients admitted to 23 intensive care units were
assigned to receive either a continuous infusion of dopamine (2µg/kg/min)
or placebo.
The researchers found no difference in peak serum creatinine concentration between
the dopamine and placebo groups (245 [standard deviation 144] vs 249
[147] µmol/L). In addition, they found that low-dose dopamine did not
reduce the number of patients requiring renal replacement therapy (35 vs
40) or the average length of stay in the intensive care unit (13 vs 14
days). No differences were found in other clinical markers of renal function.
The researchers conclude that low-dose dopamine “does not confer a clinically
significant degree of renal protection” in this group of patients but add that
a need for effective nephroprotective agents remains (Lancet 2000;356:2139).
In a leading article (ibid, p2112), Dr Helen Galley (department of medicine
and therapeutics, University of Aberdeen) comments: “The results of this well-designed
trial may at last have the desired effect on those who remain enthusiasts for
renal dose dopamine. . . . There is no justification for using renal dose dopamine
in the critically ill.”
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Obese people may be overdiagnosed with asthma, a new study indicates. Australian
researchers found that obese people with symptoms of dyspnoea and wheeze were
frequently diagnosed with asthma, although they had no evidence of airway obstruction,
reduced flow rates or airway hyperresponsiveness. The researchers comment that
the prevalence of asthma in this group was likely to be similar to that in the
rest of the population.
In contrast, the researchers found that underweight people were undertreated
for asthma. In this group, there was a significant increase in shortness of
breath and wheeze, reduced flow rates and a higher prevalence of airway hyperresponsiveness.
Underweight people had a low level of medicines use which the authors suggest
indicates undertreatment of asthma.
The study was based on pooled data of asthma and obesity prevalence from 1,971
adults (Thorax 2001:56:4).
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Alendronate (Fosamax) once-weekly 70mg tablets were launched by Merck Sharp
& Dohme this week. The product is licensed for treatment of osteoporosis
in postmenopausal women to prevent fractures.
The company says that a recent double-blind, multinational study has shown that
a once-weekly dose of 70mg alendronate is therapeutically equivalent to a 10mg
daily dose. The study showed that increases in spine, hip and total body bone
mineral density, along with reductions in biochemical markers of bone resorption
and bone formation, were equivalent for the different regimens. A lower incidence
of serious upper gastrointestinal adverse effects and a trend towards a lower
incidence of oesophageal events was seen with once-weekly 70mg dosing.
Merck Sharp & Dohme says that increases in bone density are related to the
cumulative dose of alendronate in bone, rather than the frequency of dosing,
allowing the use of a once-weekly dose without the need for a slow-release formulation.
Twenty-eight days’ supply of Fosamax Once Weekly 70mg (four tablets) costs the
same as an equivalent supply of the daily treatment regimen (net price, 28 tablets
£23.12).
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Results from a recent National Osteoporosis Society (NOS) study have revealed
that the annual spend on treatment of hip fracture is £1.7bn, or almost
£5m a day. Three years ago, estimates put the cost of treating hip fracture
at about half this figure, the charity says.
The NOS says that for a long time it has warned that the true cost of “this
largely preventable and under treated” disease was far greater than previously
calculated.
Speaking at a conference of the International Osteoporosis Foundation recently,
Mrs Linda Edwards (director, NOS) said that a strategy was needed that would
particularly direct resources to fracture prevention. She said that she hoped
that the national service framework for older people might help set priorities
for services and funding.
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A clinical trial testing the efficacy, safety and acceptability of an oral
contraceptive for men has begun, Organon Laboratories announced on January 5.
In the one-year study, 120 men from six centres in four European countries (including
the United Kingdom) will be given etonogestrel (a progestogen) 300µg daily,
together with testosterone replacement injections given every four or six weeks.
Organon says that the results of the trial are expected by the end of 2002 and,
if they are positive, a product could reach the market some time after 2005.
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Lisinopril (Zestril, Carace) is a useful prophylactic treatment for migraine,
researchers from Norway say.
Dr Harald Schrader and colleagues (department of neurology, Norwegian university
of science and technology, Trondheim) tested the efficacy of lisinopril for
this indication after observing that patients with hypertension who suffered
from migraines had fewer attacks when taking the drug.
Lisinopril treatment resulted in a reduction of about 20 per cent in the primary
efficacy parameters measured (hours with headache, number of days with headache
and number of days with migraine).
Dr Schrader et al say that most of the drugs currently recommended for
migraine prophylaxis cause adverse events that prevent their use long term but
that lisinopril was effective and well tolerated.
A total of 60 subjects were recruited for the trial. They took placebo for a
four week run-in period while the frequency of their migraine attacks was determined.
They then received either lisinopril (10mg daily for one week followed by 10mg
twice daily for 11 weeks) or a placebo (once or twice daily, as appropriate)
before undergoing a two-week washout period and then swapping to either placebo
or lisinopril for a further 12 weeks.
Complete data were obtained for 47 trial participants, as other subjects had
either not complied (n=8) or had been withdrawn from the study (n=5). Of the
patients who withdrew, three did so because of adverse events. Side effects
most commonly experienced by trial subjects included coughing, fatigue and dizziness.
The authors comment that migraine without aura seems to be more common in people
with a angiotensin converting enzyme DD gene and suggest that lisinopril might
be effective because these migraineurs have higher angiotensin converting enzyme
activity (British Medical Journal 2000;322:19).
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Clinical triallists have been warned that pregnant women being treated for
HIV with a combination of didanosine and stavudine may be at increased risk
of developing lactic acidosis.
Bristol-Myers Squibb, manufacturer of didanosine (Videx) and stavudine (Zerit),
has written to health care professionals alerting them to the risk following
three cases of fatal lactic acidosis in pregnant or postpartum women taking
the drugs. The letter says that the combination should be used with caution
during pregnancy and only if the benefit outweighs the risk (ie, when there
are few remaining treatment options).
Two cases occurred in clinical trials and a third was reported through postmarketing
surveillance. The US Food and Drug Administration has also received several
reports of non-fatal lactic acidosis in pregnant women taking the combination.
The letter was sent to all health professionals involved in clinical trials,
including some based in the United Kingdom.
Currently, both drugs carry warnings of the potential for development of lactic
acidosis. However, the FDA says that data suggest that women may be at higher
risk of this adverse reaction and that it is unclear whether it is potentiated
by pregnancy. As a result, the labelled warnings for didanosine and stavudine
will be changed in the US to include the new information.
However, no immediate change will be made in the UK. A spokeswoman for Bristol-Myers
Squibb told The Journal on January 9 that the company was waiting for
feedback from the European Agency for the Evaluation of Medicinal Products before
making a label change in Europe. She expected that a decision would be made
at the end of January or beginning of February.
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Combining capecitabine (Xeloda) with docetaxel (Taxotere) may give better
survival rates in patients with metastatic breast cancer than docetaxel alone,
say researchers.
At the 23rd annual San Antonio Breast Cancer Symposium held in the United States
recently, Dr Joyce O’Shaughnessy (Baylor-Sammons Cancer Centre, Dallas, Texas)
presented, on behalf of the Xeloda Breast Cancer Study Group, the results of
a phase III trial involving 511 women.
The women, who all had metastatic breast cancer resistant to or relapsing after
anthracycline-based treatment, were given either a combination of oral capecitabine
and intravenous docetaxel or docetaxel alone. Overall tumour response rate was
41.6 per cent in the group receiving combination treatment compared with 29.7
per cent in the docetaxel-only group. Median survival and progression-free survival
of those who received the combination were 13.7 months and 6.1 months, respectively,
compared with 11.1 and 4.2 months in the docetaxel-only group, the researchers
say.
Dr Robert Leonard (department of oncology, Western General hospital, Edinburgh),
one of the investigators involved with the trial, commented in a press release:
“Patients receiving the capecitabine-docetaxel combination had an overall 25
per cent decreased risk of death, which translates into a clinically valuable
benefit on patient survival at 12 months.”
Diarrhoea, stomatitis, nausea and “hand-foot” syndrome were more common in women
receiving combination therapy. The doses used in the study were 100mg/m2
intravenous docetaxel on day one of each 21-day treatment cycle or 1,250mg/m2
oral capecitabine twice daily on days one to 14, with one week rest, plus 75mg/m2
intravenous docetaxel on day one of each 21-day treatment cycle. Roche Pharmaceuticals,
the manufacturer of capecitabine, says that the drug is not licensed in the
United Kingdom. The company hopes to apply for a licence for treatment of metastatic
breast cancer in the summer. It adds that a licence for treatment of colorectal
cancer is expected early this year (PJ, November 4, p677).
[ Capecitabine is a fluoropyrimidine that is converted to 5-fluorouracil by
thymidine phosphorylase in malignant tissue]
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