Clinical Pharmacy News summary

A guideline on the secondary care of patients following a myocardial infarction has been issued this week by the National Institute for Clinical Excellence...[more]

Pharmacists with expertise in dermatology are ideally placed to improve the education and care of patients using dermatology products, according to the authors of a report published on April 23...[more]

Doctors have been advised to review immediately patients being treated with levacetylmethadol (Orlaam) for opioid dependence and to switch them to an alternative treatment, such as methadone...[more]

St John's wort extract is not effective as a treatment for major depression, say psychiatrists from the United States...[more]

Bicalutamide (Casodex) reduces the risk of tumour progression in nearly half of patients with early prostate cancer, trial results have revealed...[more]

IC351, a phosphodiesterase-5 inhibitor, improved erections in 64 per cent of men with diabetes-related erectile dysfunction, according to phase III data presented at the 16th annual European Association of Urology meeting in Geneva this month...[more]

A new approach to drug treatment of Alzheimer's disease is being investigated by French researchers...[more]

Micellar drug delivery combined with ultrasound can selectively and efficiently deliver drugs to drug-resistant tumour cells, say American researchers...[more]

A new conjugate vaccine to prevent meningitis caused by Neisseria meningitidis serogroup B has entered phase I trials in Belgium...[more]

A vaccine that combats the ability of the human immunodeficiency virus to mutate is being manufactured for human testing...[more]

First clinical practice guidelines from the NICE: but will they add to the NSF?

A guideline on the secondary care of patients following a myocardial infarction has been issued this week by the National Institute for Clinical Excellence. It is the first of the NICE's clinical practice guidelines that are being produced to provide practitioners with evidence-based advice. However, the value of the guideline has been called into question.

Helen Liddell, pharmaceutical and prescribing adviser, Rotherham Health Authority, told The Journal this week: “NICE guidelines are welcomed as an authoritative source from which to audit current practice but how much this guideline adds to the National Service Framework on Coronary Heart Disease is debatable.”

The guideline makes recommendations on the care of patients who have survived a myocardial infarction (MI), with the aim of decreasing subsequent early deaths. It identifies when specific drugs, such as statins, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, antiplatelet agents, calcium channel blockers and potassium channel activators, should be used. It also provides recommendations for cardiac rehabilitation and diet. Specific advice on the care of patients who have previously had an MI and have heart failure, and for patients with diabetes is also given.

Ms Liddell said that the guideline was less specific than the NSF and might be less useful in practice. “In some areas, the guideline appears contradictory. For example, it states that beta-blockers can be started at any time post-MI but then goes on to debate whether this can be safely undertaken in primary care.” Ms Liddell thought that elements of the guideline might be useful for GPs who consistently met all the NSF standards. “However, in Rotherham, rather than implementing the NICE guideline we shall be concentrating on implementing the NSF standards. For many GPs, the differences between them might be confusing,” she concluded.

The NICE says in the guideline that there is “genuine uncertainty about how to prioritise or sequence available drugs to patients presenting with a prior MI”. In terms of drug treatment, the new guideline recommends that, for patients who have had an MI and who do not have heart failure:

• Long-term treatment, first with a beta-blocker and an antiplatelet drug, and then with a statin and ACE inhibitor should be offered. (The guideline notes that not all ACE inhibitors or statins have a licence for this indication.)
• Beta-blockers and ACE inhibitors should be considered for the management of symptoms (eg, in stable angina) or risk factors (eg, hypertension).
• Calcium channel blockers, nitrates and potassium channel activators should only be used in patients who are intolerant of beta-blockers and ACE inhibitors. (Verapamil or diltiazem should be considered initially. Subsequent treatment with other drugs in these categories is then appropriate.)
• Treatment with beta-blockers, antiplatelet drugs and ACE inhibitors should be initiated while patients are in hospital. (If this does not happen, it should be initiated as soon after discharge as possible.)
• Patients discharged from hospital who are not already taking a statin should be assessed and have treatment initiated 12 weeks after the MI.

For patients with prior MI who have heart failure:

• Long-term treatment, first with an ACE inhibitor and then a beta-blocker should be offered. These patients should also be treated with an antiplatelet drug.
• Moderate to severe heart failure should be treated with spironolactone.
• Patients are likely to continue to need symptomatic treatment with a loop diuretic. In patients with mild symptoms of heart failure, spironolactone might represent a reasonable choice of adjuvant symptomatic therapy.
• There is no evidence available on whether to recommend the use of statins in this group of patients. Statin use will be influenced by clinical and practical considerations, such as whether patients were treated with them before developing heart failure.

In terms of when drug treatment should be started, the guideline states that:

• ACE inhibitors and antiplatelet drugs should be initiated while patients are in hospital or as soon after discharge as possible.
• Beta-blockers can be initiated at any time and treatment should start with low doses, which should be slowly increased, for example at fortnightly intervals, over a period of up to 12 weeks. (The guideline notes that it is unclear whether beta-blockers can be initiated safely in primary care and suggests that discussion about this should take place at a local level.)
• Spironolactone can be initiated at any time. In patients with moderate to severe symptoms of heart failure it would be reasonable to initiate spironolactone before beta-blockers.

The guideline recommends that for both groups of patients (with and without heart failure) treatment can be continued indefinitely unless there is a clear reason to stop.

For patients who have had an MI and who have diabetes, the guideline states that intensive insulin therapy initiated post-MI reduces mortality and that therapy should continue for at least three months.

The NICE's clinical practice guidelines are derived from guidelines produced by clinical and patient organisations. They are designed, says the NICE, to help health professionals and patients make the right decisions about health care in specific circumstances. The NICE says that health professionals are expected to take the guidelines fully into account when exercising clinical judgement for individual patients.

The guideline on MI is derived from a guideline originally commissioned by the Department of Health from the Centre for Health Services Research, University of Newcastle upon Tyne, and the Medicines Evaluation Group, Centre for Health Economics, University of York.

A second guideline issued this week provides recommendations on best clinical practice for avoiding pressure ulcers (see panel).

Andrew Dillon, executive director of the NICE, said of the guidelines: “The Institute is confident that they reflect best practice for the care of patients in the NHS in England and Wales.” The NICE says that local health communities will need to review existing service provision against the guidelines and that local guidelines and protocols should be reviewed and revised accordingly. The full guidelines are available on the NICE website (www.nice.org.uk).

Pressure ulcers

The guideline on pressure ulcers (bed sores) includes advice on the early identification of at-risk patients, and on the provision of preventive interventions. It does not make recommendations for wound care management of existing pressure damage.

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Pharmacists can help to improve the care of patients with skin disease

Pharmacists with expertise in dermatology are ideally placed to improve the education and care of patients using dermatology products, according to the authors of a report published on April 23.

The Dermatological Care Working Group, which produced the report, includes general practitioners, nurses, a pharmacist and a representative of the Skin Care Campaign.

The report was published “to encourage improved quality of dermatology care in the primary care setting”. Care at this level should support that given in secondary care and is not intended to compete with it, the authors say.

They add that pharmacists are key members of teams involved in development of local protocols and in defining referral pathways. In addition, community pharmacists are “well placed to ensure that patients understand how to use their prescribed treatments... Patients need to be informed about how much and how often the preparations should be used to achieve optimal results”.

Wider educational programmes targeting the public are required, particularly in relation to skin cancers, sun protection, common dermatoses, skin preparations that are available over the counter, and patient organisations, the report says.

It states that many chronic skin diseases can be well controlled by self-management, but non-compliance and incorrect use seem to be problems, particularly with topical treatments. This could be because patients are not given enough information about their disease and its treatment. It adds that even dermatologists pay little attention to instructing patients about accurate dosage of topical medication.

Services should be targeted at the treatment of conditions in which the greatest benefits will be achieved, such as eczema, psoriasis, acne and leg ulcers, the report says. The report is available from the website www.skincarecampaign.org.

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Patients taking Orlaam should be switched to alternative therapy

Doctors have been advised to review immediately patients being treated with levacetylmethadol (Orlaam) for opioid dependence and to switch them to an alternative treatment, such as methadone.

The advice comes from the European Agency for the Evaluation of Medicinal Products (EMEA) after a reassessment of the risk/benefit ratio of levacetylmethadol. The reassessment followed reports of life-threatening cardiac disorders (see PJ, January 6, p8).

The advice states that patients maintained on levacetylmethadol can be transferred directly to methadone at a daily dose of 80 per cent of the levacetylmethadol dose. The initial methadone dose must not be given until at least 48 hours after the last levacetylmethadol dose. If the patient's doctor decides to withdraw treatment completely, the EMEA says that both gradual reduction (5 to 10 per cent dose decrease each week) and abrupt withdrawal schedules have been used successfully. Patients being treated with levacetylmethadol should not stop taking the drug suddenly without seeking medical advice and should contact their prescriber immediately.

The EMEA has recommended that the drug's marketing authorisation be suspended and says that supplies of the drug are to be progressively withdrawn from pharmacies to allow patients time to switch to alternative therapies.

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St John's wort ineffective for major depression

St John's wort extract is not effective as a treatment for major depression, say psychiatrists from the United States.

Dr Richard Shelton, department of psychiatry, Vanderbilt University, Nashville, and colleagues, compared the efficacy of a standardised extract of St John's wort (up to 1,200mg daily) with placebo over eight weeks in 167 outpatients with major depression.

The number of patients who achieved a response (defined by the rate of change in score on the Hamilton Rating Scale for Depression) did not differ between the two groups. In addition, there was no significant difference between the responses of the two groups of patients when measured using other rating scales.

The researchers also analysed separately the results for patients with less severe initial depression but, again, found no difference between the placebo group and patients receiving St John's wort.

“Persons with significant major depression should not be treated with St John's wort, given the morbidity and mortality risks of untreated or ineffectively treated major depression,” the authors conclude (JAMA 2001;285:1978).

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Bicalutamide effective in early prostate cancer

Bicalutamide (Casodex) reduces the risk of tumour progression in nearly half of patients with early prostate cancer, trial results have revealed.

The study, which was presented recently at the 16th annual meeting of the European Association of Urology in Geneva, showed that after a median follow-up of 2.6 years, progression was reduced by 43 per cent in patients receiving bicalutamide 150mg plus standard care, compared with that in patients who received standard care alone. Standard care was defined as “watchful waiting”, radical prostatectomy or radiotherapy.

Mr John Anderson, consultant urological surgeon at the Royal Hallamshire Hospital in Sheffield, said: “Prolonging the time to clinical progression will confer significant benefits for patients with early prostate cancer.”

According to AstraZeneca, the manufacturer of bicalutamide, these data will form the basis of a licence submission in the UK for use of the drug to treat early prostate cancer.

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New drugs for erectile dysfunction show promise

IC351, a phosphodiesterase-5 inhibitor, improved erections in 64 per cent of men with diabetes-related erectile dysfunction, according to phase III data presented at the 16th annual European Association of Urology meeting in Geneva this month.

Men with diabetes can experience erectile dysfunction because of diabetic neuropathy.

Professor Inigo Sáenz de Tejada, of the Ramón and Cajal Hospital in Madrid, said that the 64 per cent response rate was “impressive”. In the study, 216 men with mild to severe diabetes-related erectile dysfunction were randomised to receive either placebo or IC351 at doses of up to 20mg for 12 weeks.

Treatment with IC351 significantly improved sexual function compared with placebo, regardless of the patient's age and the duration or severity of the erectile dysfunction or diabetes (25 per cent of men in the placebo group experienced an improvement in erections). Headache and dyspepsia were the most frequently reported side effects but seemed to be dose-related and transient.

Vardenafil

In another presentation at the meeting, phase II trial data for vardenafil, also a phosphodiesterase-5 inhibitor, showed that the drug improved erections and increased the ability to complete sexual intercourse.

A group of 580 men aged between 21 and 70 years with erectile dysfunction were divided into four groups and given either placebo or vardenafil 5mg, 10mg or 20mg not more than once a day.

Vardenafil improved erectile function, regardless of its cause or severity, or the age of the sufferer. Side effects were generally mild, and those most frequently experienced were headache, flushing, rhinitis and dyspepsia.

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A new approach to Alzheimer's?

A new approach to drug treatment of Alzheimer's disease is being investigated by French researchers.

Dr Agnès Petit (National Centre of Scientific Research Institute of Molecular and Cellular Pharmacology, Valbonne) and colleagues say that new synthetic drugs that are potential inhibitors of gamma-secretase might prevent the accumulation of amyloid-beta and, therefore, the progression of Alzheimer's disease.

Amyloid-beta “plaques” occur in the brains of patients with Alzheimer's disease but it is not known whether this is a cause or a consequence of the disease.

Amyloid-beta is produced from amyloid precursor protein (APP) by gamma secretase, and blocking this enzyme might prevent accumulation of amyloid-beta, the researchers say.

They add that the newly synthesised drugs act specifically on amyloid-beta production without affecting gamma-secretase cleavage at sites other than the central nervous system, and may have few side effects as a result (Nature Cell Biology 2001;3:507).

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Micelles used to target resistant cancer cells

Micellar drug delivery combined with ultrasound can selectively and efficiently deliver drugs to drug-resistant tumour cells, say American researchers.

Dr Natalya Rapoport, from the University of Utah, presented results from research using cell lines at a recent American Chemical Society meeting in San Diego.

“Our idea is to encapsulate drugs in polymeric micelles, wait for their accumulation at the tumour, and then trigger drug uptake at the tumour site by focused ultrasound,” Dr Rapoport said.

The researchers used a specific type of polymeric micelle called pluronic micelles to deliver anti-cancer drugs to multidrug-resistant cancer cells in culture. They found that drug encapsulated in pluronic micelles selectively targeted resistant cells while decreasing drug uptake by sensitive cells. Application of ultrasound increased drug uptake by both types of cell.

Dr Rapoport comments that by using these techniques together it is possible to deliver drugs selectively and efficiently to sensitive and resistant tumour cells.

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Meningococcal group B vaccine trials begin

A new conjugate vaccine to prevent meningitis caused by Neisseria meningitidis serogroup B has entered phase I trials in Belgium. The vaccine has been designed to provide protection in all age groups.

Speaking at a recent European vaccine manufacturers' conference in Switzerland, Dr Peter Fusco, senior director of microbiology and immunology, Baxter (the vaccine's manufacturer); said that the application of conjugate technology in developing the vaccine could provide protection against all meningococcal B strains.

The company says that the vaccine has been produced by attaching a chemically modified version of the meningococcal group B polysaccharide to a recombinant protein carrier, porin B. The meningococcal B protein produced appears to stimulate the immune system to produce antibodies that destroy encapsulated meningococcal B bacteria.

Baxter says that it is hopeful that the vaccine will be readily combinable with other existing, and yet to be developed, conjugate vaccines. “A combination of two conjugate vaccines for meningococcal groups B and C would prevent virtually all cases of meningococcal disease in Europe,” the company says.

Baxter expects that the vaccine will be available by 2005.

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Vaccine to combat HIV's ability to mutate

A vaccine that combats the ability of the human immunodeficiency virus to mutate is being manufactured for human testing. The manufacturer, Epimmune, plans to start trials with the vaccine, both in non-infected and infected individuals, either later this year or early next year.

In a press release issued earlier this month, the company says that the vaccine has been designed to provide immunity against several strains of HIV, including those prevalent in the United States, Europe, Africa and India.

In animal models, the vaccine was found to stimulate multiple anti-HIV cytotoxic T-cell immune responses.

Dr Mark Newman, vice-president of the infectious disease program at Epimmune, says that the vaccine is made up of protein fragments that are selected from non-mutating regions of multiple HIV proteins. “As a result, it is expected to be harder for the virus to develop variants that can escape the vaccine-induced immune response,” he says.

The company adds that the vaccine will be manufactured using technology that has been shown in animal studies to increase the efficiency of vaccine uptake by immune cells and to enhance potency.

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