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Independent prescribing became a reality in 2007 when the first pharmacist
in Britain wrote a prescription unhindered by the constraints of a clinical
management plan (PJ, 24
February 2007, p209).
Although this may have
been a fairly straightforward step for the pharmacist involved — Beth
Hird, senior practice pharmacist at Nottinghamshire County Teaching Primary
Care Trust, had already been working as a supplementary prescriber — it
was, nevertheless, a historic step for the profession.
Further progress for advanced clinical practitioners was seen throughout
the year. A rigorous accreditation process for pharmacists with special
interests was revealed in May (PJ, 5
May 2007, p515) and a consultant
pharmacist was appointed in the field of oncology.
Because of devolution, pharmacists in Scotland witnessed a different
set of developments in 2007 — electronic transfer of prescriptions
started to take hold (PJ, 8
December 2007, p642), paving the way for
the acute medication service. And the country’s minor ailment service
bedded down in 2007, with 15 per cent of people registering for the service
by June (PJ, 29
September 2007, p340).
In England and Wales, provision of clinical services under the community
pharmacy contract came under scrutiny. The value of medicines use reviews
(MURs) was questioned by MPs (PJ, 23
June 2007, p727) and research from
Keele University suggested that some pharmacists were unsure about the
difference between MURs and clinical medication reviews. A major evaluation
of the contract, presented at the British Pharmaceutical Conference in
September, revealed that 60 per cent of pharmacies were providing MURs
and prescription intervention services with 87 per cent providing at
least one enhanced service (PJ, 15
September 2007, p280). The recent
introduction of a more user-friendly MUR form (PJ, 22/29
December 2007, p701) will, perhaps, encourage pharmacists to perform
more MURs in 2008.
While pharmacy bodies continued to call for more centrally funded services
(PJ, 27 January
2007, p95), it was those negotiated locally — from
provision of unscheduled care in Dumfries and obesity management in Coventry
to a pharmacy-led service for pregnant women in Birmingham and provision
of varenicline under a patient group direction in east London — that
illustrated pharmacy’s potential for delivering clinical services.
The year ended with a vote of confidence in pharmacy when the Government
announced plans for dealing with an influenza pandemic: a consultation
suggests community pharmacists will be given powers to supply medicines
and provide services in a more flexible manner (PJ, 1
December 2007, p609).
Furthermore, Lord Darzi, the health minister
charged with leading a review of primary care services, indicated his
support for provision
of oral contraception through pharmacies without prescription (PJ, 15
December 2007, p669).
In terms of new medicines, 2007 delivered a handful of innovations
as well as the usual trickle of me-too drugs. Cardiovascular system
A new treatment option for patients with essential hypertension — aliskiren — was
launched in September by Novartis and was, arguably, the most important
new product to emerge in 2007 for fighting cardiovascular disease (see
below). Sitaxentan sodium (Thelin) was also made available to specialists
in March for the treatment of patients with pulmonary arterial hypertension.
Safety concerns in the field of cardiovascular medicine arose for aprotinin,
which lost its licence for the prevention of major blood loss during
coronary artery bypass graft surgery. (PJ, 8
December 2007, p641). Early
findings from a clinical trial suggest that the drug increases the risk
of death compared with other antifibrinolytics. Aliskiren Aliskiren (Rasilez) is the first direct renin inhibitor to
become available in the UK and is licensed either as monotherapy or for
use with other antihypertensives. (Cardiologists expect it to be used
mostly in combination.)
By inhibiting renin, aliskiren blocks the conversion of angiotensinogen
to angiotensin-I, in turn reducing the conversion of angiotensin-I to
angiotensin-II, a step that triggers vasoconstriction. Published data
suggest it could reduce systolic blood pressure by a further 4–5mmHg
when added to a high-dose angiotensin receptor blocker or the angiotensin-converting
enzyme inhibitor ramipril.
Diabetes
Patients with type 2 diabetes saw a couple of therapeutic innovations
hit the market in 2007. The new arrivals included two first-in-class
medicines — exenatide, an incretin mimetic, and sitagliptin,
a dipeptidyl peptidase type 4 inhibitor (see below). Insulin-dependent
patients, however, had their therapy options reduced when Pfizer announced
that it was to stop marketing Exubera, its inhaled
insulin
product. The company decided further investment was unwarranted after
its product failed to gain acceptance among patients and doctors.
The safety of the thiazolidinediones rosiglitazone and pioglitazone was
much debated throughout 2007: a number of studies raised concerns about
an increased risk of bone fracture and heart attack. A review of evidence
conducted by the European Medicines Agency concluded that the drugs’ benefits
continue to outweigh risks for their approved indications (PJ, 27
October 2007, p460). However, the regulator recommended careful evaluation of
individual risk when considering rosiglitazone as therapy for diabetic
patients with ischaemic heart disease.
Exenatide Developed by Lilly and Amylin Pharmaceuticals,
exenatide (Byetta) improves beta cell function by mimicking the effects
of a naturally occurring
incretin hormone protein called glucagon-like peptide-1. Exenatide also
suppresses inappropriate secretion of glucagon, decreasing beta cell
workload and increasing beta cell response. It also slows emptying of
food from the stomach
Exenatide is indicated for the treatment of type 2 diabetes in combination
with metformin or a sulphonylurea, or both, in patients who have not
achieved adequate glycaemic control on maximally tolerated doses of these
oral therapies. A benefit of this drug is that the dose does not need
to be altered to match meal size or planned activities. However, limitations
include potentially dose-limiting nausea and vomiting, and some patients
may find the twice daily injections unacceptable.
Sitagliptin Sitagliptin, marketed as Januvia by Merck, Sharp & Dohme,
prevents inactivation of incretin hormones, which are released steadily
by the intestine throughout the day and are increased in response to
a meal. Incretin hormones enhance insulin secretion and reduce glucagon
secretion, thereby reducing blood glucose levels. Incretin hormones are
inactivated by the DPP-4 enzyme and inhibitors of DPP-4 help prevent
this inactivation. Sitagliptin offers an option for add-on therapy when
either metformin or a thiazolidinedione do not provide adequate glycaemic
control with diet and exercise.
Arthritis
Patients with rheumatoid arthritis who have failed on anti-tumour necrosis
factor therapy have seen their treatment options expand with the introduction
of a new immunosuppressant, abatacept (see below).
Another anti-inflammatory agent — lumiracoxib (Prexige) — had
its marketing authorisation suspended by the Medicines and Healthcare
products Regulatory Agency in November because of concerns about liver
damage (PJ, 24 November
2007, p575).
Further restrictions on the use of piroxicam were issued in 2007 because
of the risk of gastrointestinal side effects and serious skin reactions
(PJ, 30 June 2007,
p760).
Abatacept Abatacept (Orencia) inhibits T-cell activation
and interrupts the inflammatory process in rheumatoid arthritis. Marketed
by Bristol-Myers
Squibb, it is a genetically engineered fusion protein of the cytotoxic
T-lymphocyte-associated antigen
4-Ig G1. It modulates a key co-stimulatory signal required for full activation
of T lymphocytes and reduces the effects of pro-inflammatory macrophages
and B-cells leading to a reduction in joint inflammation and destruction.
Abatacept is licensed for use in combination with methotrexate.
Malignancy
A number of therapeutic advances in oncology were seen. The most notable
new medicine was lenalidomide, launched in June by Celgene (see below).
Another antineoplastic agent, nelarabine (Atriance), was launched by
GlaxoSmithKline in September. It is licensed for the treatment of patients
with T-cell acute lymphoblastic leukaemia and T-cell lymphoblastic
lymphoma.
Licence extensions for existing therapies also bolstered the arsenal
of cancer drugs. Roche’s erlotinib (Tarceva), used in combination
with gemcitabine, gained a new indication for metastatic pancreatic cancer.
Bevacizumab (Avastin), another Roche product, widened its reach with
licence extensions for first-line treatment of metastatic breast cancer
and for advanced or recurrent non-squamous, non-small cell lung cancer
in combination with carboplatin and paclitaxel.
The market for two more
Roche products expanded with licence extensions for capecitabine (Xeloda) — for
first-line treatment of advanced gastric cancer in combination with a
platinum-based regimen — and trastuzumab (Herceptin), in combination
with an aromatase inhibitor, for the treatment of postmenopausal patients
with hormone-receptor positive metastatic breast cancer.
Other licence extensions included hepatocellular carcinoma for sorafenib
(Nexavar; Bayer) and advanced renal cell carcinoma for sunitinib (Sutent;
Pfizer).
A second human papillomavirus vaccine, GSK’s Cervarix, appeared
on the market some 11 months after the launch of Gardasil (Sanofi Pasteur/MSD)
in 2006. A national vaccination programme for 12- to 13-year-old girls
will start in 2008 (PJ, 3
November 2007, p490).
Lenalidomide The oral therapy lenalidomide (Revlimid)
has anti-neoplastic, anti-angiogenic, pro-erythropoietic and immunomodulatory
properties,
although its mechanism of action is not fully understood. It is used
in combination with dexamethasone for the treatment of multiple myeloma
in patients who have received at least one previous therapy.
A limitation
of erythropoietic agents is the potential to cause thrombosis and
they should be discontinued at haemoglobin levels above 13g/dl. Structurally
related to thalidomide, lenalidomide is contraindicated in pregnancy
and in women of childbearing potential unless conditions relating
to
contraception or abstinence are met. Infections
An interesting clinical development in the area of infectious disease
was seen when Pfizer introduced the first CCR5 antagonist for the treatment
of HIV (maraviroc) in the autumn (see below). Another protease inhibitor
reached the market in March when Janssen-Cilag launched darunavir.
Treatment options for hepatitis B expanded when Novartis launched telbivudine,
a thymidine nucleoside analogue, in June (see below).
In the field of HIV, the recall of Roche’s Viracept (nelfinavir)
in June, because of contamination with a genotoxic substance, meant that
patients, including those taking the drug as part of HIV post exposure
prophylaxis, had to switch to alternative therapies. Following a temporary
suspension of its marketing authorisation, steps were made to reintroduce
Viracept to the EU market in September.
On a more positive note, the option to reduce the pill burden of some
HIV patients came in December when Gilead launched Atripla, a fixed-combination
tablet containing efavirenz, emtricitabine and tenofovir
disoproxil.
Maraviroc Maraviroc (Celsentri) selectively binds to
the human chemokine receptor CCR5, preventing CCR5-tropic HIV-1 from
entering cells. Patients
with advanced disease harbour viruses that can enter cells via both the
CCR5 and CXCR4 co-receptors. There have been concerns that use of a CCR5
inhibitor in patients with viruses that use the CXCR4 co-receptor might
force viruses to switch to the potentially more pathogenic CXCR4-tropic
state.
Not all patients infected with HIV will be suitable to receive maraviroc
and it is licensed for treatment-experienced adult patients in whom only
CCR5-tropic HIV-1 is detectable. Another word of caution is that CCR5
antagonists could potentially impair a patient’s immune response
to some infections and this should be taken into account when treating
infections, such as active tuberculosis and invasive fungal infections.
Darunavir In common with other protease inhibitors, darunavir (Prezista)
is intended to be co-administered with ritonavir. It selectively inhibits
the cleavage of HIV-encoded polyproteins in infected cells, preventing
the formation of mature infectious virus particles.
Telbivudine Marketed as Sebivo, telbivudine is indicated
for the treatment of adults with chronic hepatitis B infection who have
compensated liver
disease and evidence of viral replication, persistently elevated serum
alanine aminotransferase levels and histological evidence of active inflammation,
or
fibrosis. The advantages of telbivudine over lamivudine appear to be
centred on larger reductions in hepatitis B virus DNA. Telbivudine is
not recommended as monotherapy for patients with established viral resistance
to lamivudine.
Eye conditions
Treatment options for neovascular (wet) age-related macular degeneration
(AMD) — a condition that results in loss of central vision — continued
to grow in 2007. February saw the launch of ranibizumab (see below),
which, like its 2006 predecessor pegaptanib sodium (Macugen), inhibits
vascular endothelial growth factor.
Another monoclonal antibody, bevacizumab, currently licensed for treatment
of certain types of cancer but not for AMD, is reported to provide visual
outcomes similar to ranibizumab, but costs less.
Ranibizumab Ranibizumab (Lucentis) is a humanised recombinant monoclonal
antibody fragment targeted against human vascular endothelial growth
factor (VEGF) A and administered by intravitreal injection. The fact
that it binds to all isoforms of VEGF-A has been suggested as a reason
why it has performed better than pegaptanib, which inhibits VEGF165 alone.
Ranibizumab is administered monthly for three consecutive months. Patients
are reviewed monthly thereafter for further visual deterioration, and
treated with further monthly injections as needed.
Ranibizumab is currently under scrutiny from the National Institute for
Health and Clinical Excellence. And although NICE appears unimpressed
with pegaptanib, the institute has suggested a novel dose-capping scheme
for ranibizumab (PJ, 22/29
December 2007, p706). Under the proposed scheme
the NHS would cover the cost of up to 14 ranibizumab injections for patients
meeting specific criteria for wet AMD, with any subsequent injections
paid for by Novartis, the drug’s manufacturer.
Other therapeutic areas
Among the remaining medicines launched during 2007 there was a handful
of firsts. Idursulfase (Shire Pharmaceuticals) is the first enzyme
replacement treatment for people suffering from Hunter syndrome. Marketed
as Elaprase, it is a purified form of iduronate-2-sulfatase lysosomal
enzyme, and is produced by recombinant DNA technology in a human cell
line.
Patients with another rare condition — paroxysmal nocturnal haemoglobinuria
(PNH) — can now be offered treatment following the launch of Alexion’s
monoclonal antibody drug eculizumab. Until now PNH patients have received
only supportive care. Eculizumab prevents the development of a protein
that mediates corpuscle destruction in PNH. Designated as an orphan drug,
eculizumab (Soliris) is the first drug to be assessed under the European
Medicines Agency’s accelerated assessment procedure.
Mircera (methoxy polyethylene glycol-epoetin beta) was launched in September
by Roche. The injection is licensed for the treatment of anaemia associated
with chronic kidney disease. The drug is the first in a new class of
erythropoiesis stimulating agents known as continuous erythropoietin
receptor activators. Compared with erythropoietin, Micera has a slower
association to and faster dissociation from the receptor, an increased
activity in vivo, as well as an increased half-life.
Other new medicines launched in 2007 are listed in Panel 1 (below).
Panel 1: Other new medicines
launched in 2007
• An allergen extract (Grazax) developed by ALK-Abelló. The
sublingual tablet is licensed for grass-pollen-induced rhinitis and
conjunctivitis.
• A chewable tablet containing lanthanum carbonate (Fosrenol) launched
by Shire. Lanthanum is a non-calcium phosphate binding agent used
to control hyperphosphataemia in chronic renal failure patients
on dialysis.
• Paliperidone (Invega), a once daily, prolonged-release atypical
antipsychotic from Janssen-Cilag. It is an active metabolite of
risperidone and is not extensively metabolised in the liver.
• Mecasermin (Increlex; Ipsen), a recombinant human insulin-like
growth factor-1 for the long-term treatment of growth failure in
children and adolescents with severe primary insulin-like growth
factor 1 deficiency.
• A novel anticonvulsant — rufinamide (Inovelon) — launched
by Eisai. The drug is for patients with Lennox-Gastaut syndrome,
a severe and difficult-to-treat form of epilepsy that begins in childhood.
• Colesevelam hydrochloride (Cholestagel; Genzyme). The drug, the
first of its kind to be available in the UK in tablet form, impedes
the reabsorption of bile acids in the intestine. It is used to
reduce low density lipoprotein-cholesterol levels in patients with
primary
hypercholesterolaemia.
• An antifungal agent anidulafungin (Ecalta) launched by Pfizer.
This echinocandin antimycotic is used for the treatment of invasive
candidiasis in adults who are not neutropenic. |
Safety concerns and new guidance
In addition to the safety concerns outlined above, UK and European
regulators issued advice about allergic reactions to strontium ranelate
(PJ, 24
November 2007, p579) and the risks associated with erythropoietins
and overcorrection of haemoglobin concentrations in patients with
chronic renal disease (PJ, 8
December 2007, p637).
They also recommended
stronger
warnings about the risk of depression in overweight patients treated
with rimonabant (Acomplia) and in smokers trying to quit with the
help of varenicline (Champix) (PJ, 22/29
December 2007, p706).
New guidance on the use of medicines in the NHS issued in 2007 is
highlighted in Panel 2 (below).
Panel 2: New guidance
Recommendations on the cost-effective use of medicines
within the NHS continued to be made by NICE, the Scottish Medicines
Consortium
and the All-Wales Medicines Strategy Group. Their rulings can
be found online (www.nice.org.uk, www.scottishmedicines.org.uk and www.wales.nhs.uk, respectively).
Technology appraisals conducted by NICE included those on: • Adalimumab, etanercept and infliximab for ankylosing spondylitis
• Naltrexone as relapse prevention for drug misusers and methadone
and buprenorphine for opioid-dependency
• Ezetimibe for primary hypercholesterolaemia
• Cincelet for secondary hyperparathyroidism
• Omalizumab for uncontrolled asthma
• Bortezomib for multiple myeloma
As part of its bortezomib guidance, NICE gave the go-ahead for
a scheme in which the NHS is refunded the cost of the drug by the
manufacturer in cases where patients fail to respond adequately
(PJ, 27
October 2007, p461).
Halfway through the year, NICE also successfully defended its guidance
on the use of Alzheimer’s drugs, which had been challenged
in the High Court. The court rejected claims that NICE had acted
irrationally and unfairly in reaching its recommendation that patients
with moderate Alzheimer’s disease, but not those with mild
disease, should receive donepezil, galantamine or rivastigmine
(PJ, 18
August 2007, p169). |
POM-to-P switches
2007 did not bring any major POM to P switches. However, a number of
proposals were made and pharmacists can expect to see the following
medicines on pharmacy shelves before 2008 is out:
• Tranexamic acid for heavy menstrual bleeding
• Naproxen for dysmenorrhoea
• Azithromycin for asymptomatic chlamydia infection
• Diclofenac for short-term relief of headache, dental pain, period
pain, rheumatic and muscular pain, backache and the symptoms of colds
and influenza
These and other clinical developments will be covered in The Journal’s
news pages as they happen.
ACKNOWLEDGMENT Katrina Simister, managing editor, new medicines scheme,
National Prescribing Centre.
Identify knowledge gaps
1. Can you list three new drugs launched last
year?
2. Which innovative product for diabetes did Pfizer decide to stop marketing
in 2007 because it had failed to gain acceptance from patients and prescribers?
3. Concerns about possible liver damage led to the suspension of which
anti-inflammatory drug’s marketing authorisation in 2007?
Before reading on, think about how this article
may help you to do your job better. The Royal Pharmaceutical
Society’s areas of competence for pharmacists are listed
in “Plan
and record”
This article relates to “drug therapy” (see
appendix 4 of “Plan and record”).
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Action: practice
points
Reading is only one way to undertake CPD and the Society will expect
to see various approaches in a pharmacist’s CPD portfolio.
1. Which medicines launched in 2007 will have most relevance to your
practice? Collate any information on these drugs that might be useful
for your patients.
2. Consider what advice you might give to a patient who is using rimonabant.
3. Check the websites of NICE, the SMC or the AWMSG for guidance launched
in 2007. Discuss the three most relevant pieces of guidance with a colleague.
Evaluate
For your work to be presented as CPD, you need to evaluate your reading
and any other activities. Answer the following questions:
What have you learnt?
How has it added value to your practice? (Have you applied this learning
or had any feedback?)
What will you do now and how will this be achieved?
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