Clinical Pharmacy News summary

MS drug treatments compared Clinical trials results have indicated that there could be differences in the efficacy of newer drug treatments for relapsing-remitting multiple sclerosis (MS)...[more]

MS sufferers could benefit from combination therapy Patients with relapsing-remitting or secondary progressive multiple sclerosis (MS), who do not respond to monotherapy with interferon beta-1b (Betaferon), might benefit from the addition of mitoxantrone (Novantrone, Onkotrone)...[more]

Primary care practitioners need to become “genetically literate” Primary care practitioners must become “genetically literate” to cope with likely increases in the availability of DNA-based tests, and the demand from patients for genetic information and advice...[more]

Children not affected by sedating antihistamines Antihistamines might have different sedating properties in children and adults, American researchers suggest...[more]

NICE guidance on gemcitabine issued Guidance on the use of gemcitabine (Gemzar) for pancreatic cancer has been issued by the National Institute for Clinical Excellence this week...[more]

Botulinum toxin guidelines issued Guidelines on the use of botulinum toxin for treatment of spasticity were launched in London at the end of last month...[more]

Inappropriate prescribing in the elderly hard to change A medication review programme, aimed at reducing the number of potentially inappropriate prescriptions (PIPs) given to elderly patients, has not reduced polypharmacy, a Canadian study has shown...[more]

Concerns raised over safety of propofol Safety concerns about the use of propofol (Diprivan) in children have been raised by the United States Food and Drug Administration (FDA)...[more]

Drug-resistant HIV increasing in UK Transmission of drug-resistant human immunodeficiency virus-1 (HIV-1) in the United Kingdom is increasing...[more]

Stress management and tricyclics reduce chronic tension headaches by half A combination of a tricyclic antidepressant and stress management therapy can reduce the frequency of chronic tension headache by as much as a half, say researchers from Ohio University...[more]

Oral warts linked to antiretrovirals Patients taking antiretroviral therapy might have an increased risk of developing oral warts, according to researchers from the University of California, San Francisco, United States...[more]

Link between DVT and long-haul air travel still to be resolved The results of the first prospective, randomised, controlled trial to assess the risk of symptomless deep-vein thrombosis associated with air travel have been published this week in The Lancet...[more]

MS drug treatments compared

Clinical trials results have indicated that there could be differences in the efficacy of newer drug treatments for relapsing-remitting multiple sclerosis (MS).

Dr Omar Khan, department of neurology, Wayne State University School of Medicine, Detroit, United States, and colleagues conducted an open-label, non-randomised study involving 156 patients with relapsing-remitting MS who had not previously received treatment for the disease.

The aim of the study was to compare the effect of no treatment, interferon beta-1a (Avonex), interferon beta-1b (Betaferon) and glatiramer acetate (Copaxone) on relapse rate.

Compared with untreated patients, subject given interferon beta-1b or glatiramer had a significant reduction in relapse rate, whereas there was no significant reduction in those treated with interferon beta-1a. “The results of this study indicate that treatment with immunomodulating therapy is beneficial compared to no treatment in treatment-naive relapsing-remitting MS patients,” the researchers say.

The mean number of relapses at the end of the one-year trial period was 0.97 in the untreated controls, 0.85 in those receiving interferon beta-1a (P value = 0.309), 0.61 in the interferon beta-1b group and 0.62 in patients receiving glatiramer (P values = 0.002 and 0.003, respectively; confidence intervals not given).

The researchers also calculated the percentage change in relapse rate for the groups. This increased in untreated subjects by 2.53 per cent and decreased by 23.3 per cent, 43 per cent and 37.8 per cent in the interferon beta-1a, interferon beta-1b and glatiramer groups, respectively.

A relapse was defined as the appearance of new, or worsening of previous, neurological symptoms lasting at least 48 hours, accompanied by objective change on neurological examination, in a patient who had been clinically stable for the previous four weeks.

Patients received either 6 million units (30µg) interferon beta-1a intramuscularly weekly, 8 million units (250µg) interferon beta-1b subcutaneously on alternate days or 20mg glatiramer subcutaneously daily.

Dr Khan and colleagues note that the fact that the trial was non-randomised and open-label was a limitation but that this method was intended to mirror clinical practice (European Journal of Neurology 2001:8;141).

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MS sufferers could benefit from combination therapy

Patients with relapsing-remitting or secondary progressive multiple sclerosis (MS), who do not respond to monotherapy with interferon beta-1b (Betaferon), might benefit from the addition of mitoxantrone (Novantrone, Onkotrone).

This was the conclusion of Professor Douglas Jeffrey, department of neurology, Wake Forest University Baptist Medical Centre, North Carolina, United States, who presented the findings of a pilot study at the annual meeting of the American Academy of Neurology in Philadelphia on May 10.

The study involved 10 patients with aggressive relapsing-remitting or secondary progressive MS, who continued to have attacks or relapses and who continued to develop brain plaques visible on magnetic resonance imaging (MRI) scans during at least six months of treatment with interferon beta-1b. The researchers found that when mitoxantrone was added to the patients' therapy for six months, relapses and new lesions were reduced by 50 per cent. “The combination therapy shows excellent promise for patients who are not successfully controlled on monotherapy,” Professor Jeffery said.

Mitoxantrone received a licence for MS treatment in the US last year but is not licensed for this indication in the United Kingdom. Both Wyeth, the UK manufacturer of Novantrone, and ASTA Medica, the UK manufacturer of Onkotrone, told The Journal on May 9 that MS was not an area that they were currently researching, and neither company had plans to apply for a licence for treatment of the disease.

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Primary care practitioners need to become “genetically literate”

Primary care practitioners must become “genetically literate” to cope with likely increases in the availability of DNA-based tests, and the demand from patients for genetic information and advice.

This is the view of Dr Jon Emery, department of public health and primary care, University of Cambridge, and Professor Susan Hayflick, Oregon Health Sciences University, Portland, United States.

Dr Emery and Professor Hayflick say that genetic medicine is already beginning to enter primary care in the form of testing for predisposition to certain cancers, and as screening and diagnostic tests for common recessive disorders, such as cystic fibrosis. Traditionally, clinical geneticists have dealt with counselling of couples and families affected by genetic disorders.

However, increasing use of genetic information to tailor drug selection and dosage and to predict the risk of developing common conditions, such as diabetes and cardiovascular disease, means that, soon, clinical genetics services will be overwhelmed.

Primary care is well placed to support an integrated genetic service, they say. “We must not miss this opportunity to prepare primary care.” (BMJ 2001;322:1027).

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Children not affected by sedating antihistamines

Antihistamines might have different sedating properties in children and adults, American researchers suggest.

A study involving 63 children aged between eight and 10 years found that neither diphenhydramine nor loratadine had an effect on alertness or ability to learn. Researchers from the National Jewish Medical and Research Centre say that the study highlights physiological differences between adults and children, and raises doubts over the assumed effects of antihistamines in children. The study will be published in the May issue of The Journal of Pediatrics.

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NICE guidance on gemcitabine issued

Guidance on the use of gemcitabine (Gemzar) for pancreatic cancer has been issued by the National Institute for Clinical Excellence this week. Andrew Dillon, NICE chief executive, said in a press release on May 8: “Gemcitabine is a clinically and cost effective way to offer patients additional months of life.”

The guidance states that gemcitabine can be offered as first-line chemotherapy to patients with advanced pancreatic cancer if they have a Karnofsky performance score of 50 or more (the Karnofsky performance score is a measure of a patient's ability to perform certain ordinary tasks). It adds that patients who are suitable for curative surgery or who have a Karnofsky performance score of less than 50 should not be offered gemcitabine.

The guidance has been welcomed by Health Minister John Denham and Welsh Assembly Health Minister Jane Hutt. In a press release issued on May 8 by the Department of Health, Mr Denham said: “Stamping out the post-code lottery of care is one of the Government's top priorities.” The Department expects the guidance to lead to gemcitabine being offered more consistently to certain patients diagnosed with pancreatic cancer — since it was licensed in 1995, its uptake across the United Kingdom has been variable.

The NICE estimates that the total number of patients requiring gemcitabine would be 600 to 840 per year and that, based on this number, the total additional cost to the National Health Service would be between £816,000 and £3m per year. Copies of the full guidance are available on the NICE website (www.nice.org.uk).

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Botulinum toxin guidelines issued

Guidelines on the use of botulinum toxin for treatment of spasticity were launched in London at the end of last month.

Recommendations are made about the correct selection of patients for botulinum toxin treatment, follow-up, documentation, and training of clinicians in administering the toxin. Dr Anthony Ward, consultant in rehabilitation medicine at the North Staffordshire Rehabilitation Centre, said that the document “aims to assist clinicians treating adults with spasticity by providing guidance on the correct use of botulinum toxin as part of an overall patient management programme”.

Botulinum toxin is a local muscle relaxant, which reduces the effects of localised spasticity such as pain and spasm.

Copies of “The management of adults with spasticity using botulinum toxin: a guide to clinical practice” are available free from Freepost (KT4211), Byfleet, Surrey KT14 7DR.

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Inappropriate prescribing in the elderly hard to change

A medication review programme, aimed at reducing the number of potentially inappropriate prescriptions (PIPs) given to elderly patients, has not reduced polypharmacy, a Canadian study has shown.

Dr Jacques Allard, of the department of family medicine at the University of Sherbrooke in Quebec, and colleagues carried out a randomised, controlled trial involving 266 patients aged over 75 years to evaluate the impact of an intervention programme on the prescribing of PIPs.

The programme involved a review of patients' drugs and diagnoses by a multidisciplinary team which included a pharmacist. The team analysed patients' drug profiles and identified possible problems. They then sent suggestions to the patients' general practitioners, along with documentation justifying their recommendations. A total of 147 recommendations were made by the team, 37 of which were accepted by the patients' general practitioners. The researchers suggest that the low level of acceptance could have been influenced by a lack of consensus on certain questions related to drug use (for example, whether to treat hyperlipidemia in patients over 75 years of age).

To assess the impact of the intervention programme, the number of PIPs was measured both before and after the programme, with a one-year period between the two measures. The researchers found that the mean number of PIPs per patient in the experimental group (assigned to the intervention) fell by 0.24 (standard deviation, 0.69) compared with 0.15 (standard deviation, 0.52) in the control group. The difference was not statistically significant.

The researchers comment that the lack of effect of the intervention programme might have been because it only involved a single intervention over a one-year period. “Many events could have occurred ... which could have had an impact on the drug profile.”

The study is published in the Canadian Medical Association Journal (2001;164: 1291).

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Concerns raised over safety of propofol

Safety concerns about the use of propofol (Diprivan) in children have been raised by the United States Food and Drug Administration (FDA).

The FDA has written to health care providers in the US to highlight concerns about the use of propofol for sedation of paediatric patients in intensive care.

The issue was highlighted following a study of 327 paediatric patients that compared propofol (1 and 2 per cent) with other medicines, such as lorazepam, chloral hydrate, fentanyl, ketamine, morphine and phenobarbital. The study showed an increase in the number of deaths in patients treated with propofol compared with the other treatments. The FDA says: “Careful review of the deaths failed to reveal a correlation with underlying disease status; nor did the review reveal a definite pattern to the causes of death.” It recommends that further trials are needed.

A spokeswoman for AstraZeneca, the manufacturer of propofol, told The Journal on May 1 that the company was not planning to issue a similar letter in the United Kingdom. Any such action would be taken in consultation with the appropriate regulatory bodies, she said.

AstraZeneca has evaluated data from the study and believes that there is no causal relationship between the use of propofol and the deaths.

The spokeswoman said that the current licensed indications for propofol did not include sedation of children aged under 16 years in intensive care (this is also the case in the US). The data from the trial have no implication for propofol's use for adult sedation, she added.

A spokeswoman for the Medicines Control Agency told The Journal on May 1 that propofol was not licensed for the indication examined in the trial and that the Committee on Safety of Medicines had previously reminded UK doctors that propofol is not recommended for unlicensed use.

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Drug-resistant HIV increasing in UK

Transmission of drug-resistant human immunodeficiency virus-1 (HIV-1) in the United Kingdom is increasing. New approaches to encourage safer sexual behaviour within all sectors of the population are urgently needed, according to Dr Kholoud Porter and colleagues from the UK Collaborative Group on Monitoring the Transmission of HIV Drug Resistance.

The researchers evaluated 69 patients between June 1994 and August 2000 for the development of drug resistance within 18 months of becoming infected with HIV. Drug resistance was detected in 14 per cent of these patients and was found to be associated with reverse transcriptase or protease gene mutations. The risk of being infected with drug-resistant virus increased over time and the estimated prevalence of transmitted drug-resistance in people infected with HIV in 2000 was 27 per cent.

The researchers comment: “As unprotected sex among those at highest risk of HIV infection increases, the likelihood of being infected by a person who has taken antiretroviral drugs is increased”. They add that the prevalence of drug resistance in people infected with HIV may be increasing because highly active antiretroviral therapy (which includes two nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or one or two protease inhibitors [British National Formulary, March 2001]) was being used more often. The study is published in the BMJ (2001;322:1087).

Another study, presented recently at the seventh annual conference of the British HIV Association, showed that after six months of treatment, a regimen containing efavirenz had a higher rate of success than a regimen containing nevirapine or a protease inhibitor. The data were obtained from a database held at the Chelsea and Westminster Hospital and the Royal Free and University College Medical School, London, and involved 888 patients.

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Stress management and tricyclics reduce chronic tension headaches by half

A combination of a tricyclic antidepressant and stress management therapy can reduce the frequency of chronic tension headache by as much as a half, say researchers from Ohio University.

A total of 203 patients who suffered chronic tension headache were randomised to one of four treatments — placebo, a tricyclic antidepressant (up to 100mg amitriptyline daily, as tolerated), stress management therapy, or a combination of a tricyclic and stress management therapy.

Dr Kenneth Holroyd, department of psychology, and colleagues found that patients receiving any treatment experienced a reduction in headache activity compared with the placebo group.

However, about two-thirds of the subjects who received combined treatment experienced a reduction in the severity of headaches of at least 50 per cent, compared with about one-third of the subjects who received either a tricyclic or stress management therapy alone.

The stress management therapy included muscle stretching exercises, relaxation techniques and instruction on identifying and managing stressors that led to headaches. Patients who could not tolerate amitriptyline were given nortriptyline (up to 75mg daily, as tolerated) (JAMA 2001; 285:2208).

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Oral warts linked to antiretrovirals

Patients taking antiretroviral therapy might have an increased risk of developing oral warts, according to researchers from the University of California, San Francisco, United States.

A study of 1,280 patients showed that patients given highly active antiretroviral therapy (HAART) had a six-fold increase in incidence of oral warts compared with patients not taking antiretrovirals. Patients given antiretroviral therapy, as opposed to HAART, had a three-fold increase.

The increase in the occurrence of oral warts, and its apparent association with antiretroviral therapy, was somewhat unexpected, although a link had been suggested previously, Dr Deborah Greenspan, department of stomatology, and colleagues comment. They note that some opportunistic infections can occur as CD4 cell counts improve: “The reconstitution of the immune system might be functionally incomplete and its effectiveness might, therefore, vary. This situation could lead to the development of oral warts, in the context of an overall reduction in opportunistic infections.” (Lancet 2001;357:1411.)

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Link between DVT and long-haul air travel still to be resolved

The results of the first prospective, randomised, controlled trial to assess the risk of symptomless deep-vein thrombosis associated with air travel have been published this week in The Lancet (2001;357: 1485).

Data from the study, led by John Scurr, consultant surgeon at University College and Middlesex Hospital, London, suggest a link between DVT and long-haul air travel. However, the authors of an accompanying leading article argue that the issue remains unresolved (ibid, p1461).

Mr Scurr and colleagues found that of 200 passengers taking a long-haul flight, those wearing compression stockings throughout the flight had no evidence of symptomless DVT (assessed by ultrasonography within 48 hours of flying). Of the passengers not wearing compression stockings, 10 per cent were found to have symptomless DVT in their calf veins.

Jack Hirsh and Martin O'Donnell from McMaster University, Ontario, Canada, say, in the accompanying leading article, that the reported incidence of symptomless thrombosis among the controls in Mr Scurr's study was at least 40-fold higher than previous estimates. They suggest that the high reported rate might have been due to biased ultrasonographic assessment. They add that the positive ultrasonographic tests in Scurr's study were not confirmed by venography.

Dr Hirsh comments: “If the results of the randomised trial are valid, they should be easy to reproduce, and if confirmed they would clearly establish lengthy air travel as an important risk factor for thrombosis.”

He adds that until more definitive information becomes available, it is reasonable to continue to recommend simple measures for long-distance travellers, such as regular muscle contraction and adequate hydration.

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