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The Pharmaceutical Journal Vol 266 No 7148 p668-670
May 19, 2001

Clinical Pharmacy News summary

Role for pharmacists in reducing the problem of benzodiazepine addiction — according to Sheena Macgregor, prescribing adviser for Borders Primary Care NHS Trust, Roxburghshire, Scotland...[more]

Appetite suppressants lose their licences again The licences for the appetite suppressants phentermine (Duromine, Ionamin) and amfepramone (Tenuate Dospan) have been withdrawn for a second time...[more]

Treatment for actinic keratosis launched A new treatment for patients with the pre-cancerous skin condition actinic keratosis is now available following the launch of Bioglan's Solaraze...[more]

Serious risks associated with terbinafine and itraconazole The United States Food and Drug Association has warned American health care professionals that itraconazole (Sporanox) tablets have been linked with a risk of developing congestive heart failure, and that both itraconazole (Sporanox) and terbinafine (Lamisil) tablets can cause liver failure...[more]

Weekly contraceptive patch could be as effective as OC A contraceptive patch (Ortho Evra) appears to be as effective as oral contraceptives (OCs) in preventing pregnancy and could be easier to use, trial results suggest...[more]

Malarone gains licence for malaria prophylaxis Malarone (atovaquone/proguanil) is now available for the prophylaxis of Plasmodium falciparum malaria, in addition to its existing indication for the treatment of malaria...[more]

Polio vaccine not to blame for HIV pandemic Three articles published in Nature have refuted suggestions that an oral polio vaccine used in Africa during the 1950s began the pandemic of HIV-1...[more]

Role for montelukast in allergic rhinitis Montelukast is useful in treating seasonal allergic rhinitis, a new study shows. The drug was found to provide relief from symptoms such as nasal congestion on awakening...[more]

Effective prevention of chronic kidney transplant rejection New trial results suggest that tacrolimus (Prograf) and the Neoral formulation of ciclosporin are better at preventing long-term rejection of transplanted kidneys than the older Sandimmune preparation...[more]

APBI report warns that UK could lose its leading role in genomics research If the use of new medicines in the United Kingdom is not encouraged, then the research, development and manufacture of these products will be carried out elsewhere, according to a report published this week by the Association of the British Pharmaceutical Industry...[more]

Raising the profile of indigestion A leaflet intended to raise awareness of the causes, symptoms and types of indigestion, and to help people visiting a pharmacy to describe their symptoms properly, has been launched...[more]

Alzheimer's disease linked to low vitamin levels Low levels of vitamin B₁₂ or folate might predispose people to developing Alzheimer's disease (AD), researchers suggest...[more]

Role for pharmacists in reducing the problem of benzodiazepine addiction

Pharmacists have a role to play in assisting patients addicted to benzodiazepines, according to Sheena Macgregor, prescribing adviser for Borders Primary Care NHS Trust, Roxburghshire, Scotland.

Ms Macgregor told The Journal on May 16 that, despite increased medical and public awareness of the long-term effects of benzodiazepines, many patients still requested sleeping tablets, or “something to help them cope” with a difficult life event.

Ms Macgregor's comments follow a BBC Panorama programme that highlighted the degree to which benzodiazepines are being prescribed in the United Kingdom. The programme's presenter claimed that more than one million adults in Britain were addicted to tranquillisers prescribed by their general practitioners. This was despite guidance that was issued in 1988 by the Committee on Safety of Medicines, which stated that benzodiazepines should not be prescribed for more than four weeks at a time.

Speaking on the programme, which was broadcast on May 13, Professor Louis Appleby, the National Director for Mental Health at the Department of Health, said: “There are seven million prescriptions each year for these drugs but our data does not tell us how many people are on them long-term.” He added that changing prescribing practice required more than just guidelines, and that practice changed slowly.

Commenting on what pharmacists could do to help alleviate the problem, Ms Macgregor said that prescribing advisers should recommend that benzodiazepines are not added to computer repeat prescription records. This would avoid patients accessing further supplies without their GP reviewing the prescription. “Patients need to be advised that the prescription is for a few weeks only and should be informed of the alternative options that are available.” She added that, in some areas, alternative resources could be an option, for example, sleep clinics, community psychiatric nursing or clinical psychology support.

Ms Macgregor added that prescribing advisers could encourage GPs to review benzodiazepine prescribing and assist them with developing withdrawal strategies. Practice-based and community pharmacists could also provide support for motivated patients to discontinue their medication gradually.

Professor Martin Kendall, chairman of the Joint Formulary Committee of the British National Formulary, told The Journal on May 16: “In the right context, benzodiazepines have an important place in therapeutics, but, despite clear guidance on how they should be prescribed, there are still some concerns about inappropriate use.

“The Joint Formulary Committee recognises that doctors still see individuals who have become dependent on benzodiazepines. This is why the BNF not only describes the effects of benzodiazepine dependence and sudden withdrawal but it continues to offer advice on how patients are best weaned off the drug.”

BNF guidance

The guidance, which is summarised in the British National Formulary (No 41, p166), states:

Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic or psychotic illness.
The use of benzodiazepines to treat short-term “mild” anxiety is inappropriate and unsuitable.
Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or subjecting the individual to extreme distress

The BNF also provides guidance on withdrawal of benzodiazepines. It states that a benzodiazepine can be withdrawn in steps of about one-eighth of the daily dose every fortnight. It also suggests a protocol for patients who have difficulty withdrawing from the drugs.

Appetite suppressants lose their licences again

The licences for the appetite suppressants phentermine (Duromine, Ionamin) and amfepramone (Tenuate Dospan) have been withdrawn for a second time.

The products first lost their United Kingdom licences in April 2000 (see PJ, April 15, 2000, p572) but had them reinstated after challenges to the decision by the drugs' respective manufacturers (see PJ, April 29, 2000, p646 and August 19, 2000, p260). The latest withdrawals follow legal action and are not due to any new safety concerns, says the Medicines Control Agency.

The MCA adds that the withdrawal should be completed by June 10, 2001, and has advised pharmacists that they should retain enough stock to fill prescriptions until this date. After June 10, all stocks should be returned to suppliers.

The MCA has also issued prescribing advice, stating that no further patients should be started on the two drugs. Prescribers are advised that dosage reduction of phentermine or amfepramone should be gradual, over at least two weeks, to reduce the risk of withdrawal symptoms.

Treatment for actinic keratosis launched

A new treatment for patients with the pre-cancerous skin condition actinic keratosis is now available following the launch of Bioglan's Solaraze.

Solaraze contains a high concentration of the non-steroidal anti-inflammatory drug diclofenac (3 per cent), which is antidysplastic, in a hyaluronan vehicle. The product is formulated to produce a depot of diclofenac in the epidermis. Commenting on the launch, Dr Barry Monk, consultant dermatologist, Bedford Hospital NHS Trust said on May 10: “Solaraze can be used easily in dermatology clinics to treat large or small areas. It has been effective at reducing the number of actinic keratoses, and is a generally well-tolerated medicine.” He added that the product could offer benefits over existing treatments, which often caused inflammation of the treated area.

Actinic (solar) keratoses are common dysplastic epidermal lesions (areas of thickened, scaly skin) that are thought to be caused by ultraviolet exposure, and which can progress to become squamous cell carcinoma. Existing treatment options for actinic keratoses include cryotherapy and topical fluorouracil.

Serious risks associated with terbinafine and itraconazole

The United States Food and Drug Association has warned American health care professionals that itraconazole (Sporanox) tablets have been linked with a risk of developing congestive heart failure, and that both itraconazole (Sporanox) and terbinafine (Lamisil) tablets can cause liver failure.

The FDA is advising that itraconazole should not be used to treat onychomycosis (fungal infections of the nails) in patients with ventricular dysfunction, such as congestive heart failure (CHF) or a history of CHF. In a recent review of 94 US and international spontaneous post-marketing reports received between September 1992 and April this year, the FDA identified 58 cases linking itraconazole with the development of CHF. Death occurred in 13 of these patients, but the causal relationship was unclear as 10 patients had serious underlying conditions.

In addition, the FDA says that both terbinafine and itraconazole have been associated with serious liver problems, including liver failure and death. Some cases involved patients who had neither pre-existing liver disease nor a serious underlying medical condition. The FDA says that since April this year, it has become aware of 16 cases of liver failure associated with terbinafine tablets, of which 11 resulted in death and two in liver transplantation. As of March this year, the FDA was also aware of 24 cases of liver failure (including 11 deaths) associated with using itraconazole for the treatment of either onychomycosis or systemic fungal infections.

The FDA says that the labelling for both products has been updated and now includes additional contraindications and precautions. Because of the risks associated with both drugs, it is also recommended that health care providers obtain nail specimens for laboratory testing in order to confirm diagnosis before prescribing. The FDA says that the hepatic warning does not apply to topical terbinafine preparations.

The summaries of product characteristics and labelling for both products have yet to be updated in the United Kingdom. A spokesman for Janssen-Cilag, manufacturer of Sporanox, told The Journal on May 15 that changes had been submitted to the Medicines Control Agency and a response was expected shortly. Novartis Pharmaceuticals, manufacturer of Lamisil, told The Journal on May 16 that it was in the process of updating the product's SPC.

Weekly contraceptive patch could be as effective as OC

A contraceptive patch (Ortho Evra) appears to be as effective as oral contraceptives (OCs) in preventing pregnancy and could be easier to use, trial results suggest.

Dr Marie-Claude Audet of the Halles de Ste-Foy Medical Centre, Quebec, Canada, and colleagues randomised 1,417 women of child-bearing potential to receive either a weekly transdermal patch or a triphasic oral contraceptive for either six or 13 menstrual cycles.

Both forms of contraception were as effective as each other at prevention of pregnancy and at reducing the incidence of breakthrough bleeding, but the patch users were more likely to comply with the treatment.

The percentage of cycles in which there was perfect compliance was 88.7 per cent with the patch and 79.2 per cent with the oral contraceptive. The matrix patch delivered 150µg norelgestromin and 20µg ethinylestradiol daily, and was used for three consecutive weeks followed by a patch-free week. It could be applied to the buttocks, upper outer arm, lower abdomen or upper torso (excluding the breasts). A total of 4.6 per cent of all patches were replaced because they became detached, including 2.8 per cent for partial detachment. The oral contraceptive was taken daily from days 1 to 21 followed by placebo for days 22 to 28.

The most commonly experienced side effects in both groups included headache, nausea, breast discomfort and dysmenorrhoea. About 20 per cent of women using the patch experienced application site reactions, although only 2.6 per cent of these discontinued use as a result (JAMA 2001;285:2347).

A spokeswoman for Janssen-Cilag, the manufacturer of the patch, told The Journal on May 16 that it had filed a marketing authorisation for the product with the European Agency for the Evaluation of Medicinal Products in March 2001.

Malarone gains licence for malaria prophylaxis

Malarone (atovaquone/proguanil) is now available for the prophylaxis of Plasmodium falciparum malaria, in addition to its existing indication for the treatment of malaria.

For prophylaxis, it should be started 24 or 48 hours before arrival in an area where malaria is endemic, and continued for seven days after leaving the area. The summary of product characteristics states that, when Malarone is used, the period of stay in the malaria-endemic area should not exceed 28 days. GlaxoSmithKline, manufacturer of the product, says that the short dosing regimen should significantly improve compliance with malaria prophylaxis.

Commenting on the additional indication for the drug, Dr Larry Goodyer, senior lecturer in clinical pharmacy at Kings College London, said: “Malarone is an important new option for malaria prophylaxis. Current evidence indicates that it will give a high level of protection combined with a good side effect profile.”

Polio vaccine not to blame for HIV pandemic

Three articles published in Nature have refuted suggestions that an oral polio vaccine used in Africa during the 1950s began the pandemic of HIV-1 (2001;410:1045, 1046 and 1047).

The theory had been that early batches of live oral polio vaccine grown in chimpanzee kidney cell cultures had become contaminated with a chimpanzee simian immunodeficiency virus (SIV), which had become able to infect a human host.

The first two articles show that none of the vaccines given in the 1950s were prepared with chimpanzee kidneys — macaque monkey kidneys were used. As monkey SIV is only distantly related to HIV, it cannot have been its precursor. The authors of the third article looked at the evolutionary development of HIV-1 and say that analysis of its sequences indicates that the main group of viruses originated before the 1950s vaccination campaign, supporting a model of “natural transfer” from chimpanzees to humans.

Role for montelukast in allergic rhinitis

Montelukast is useful in treating seasonal allergic rhinitis, a new study shows. The drug was found to provide relief from symptoms such as nasal congestion on awakening.

In the two-week study, Dr George Philip, medical director, Merck (United States) and colleagues, randomly assigned 1,302 patients, aged between 15 and 81 years, with seasonal allergic rhinitis to receive either montelukast 10mg, loratadine 10mg or placebo, once daily, during the spring allergy season.

Treatment with montelukast, which is currently licensed in the United Kingdom for prophylaxis of asthma, improved night-time symptoms associated with seasonal allergic rhinitis. The researchers say that montelukast, a leukotriene receptor antagonist, may improve symptoms by reducing underlying inflammatory processes. In the study, a reduction in peripheral blood eosinophils (inflammatory cells activated by leukotrienes) was seen with montelukast. Loratadine was found to improve night-time symptoms but had no significant effect on peripheral blood eosinophils compared with placebo.

The data were presented last week at the European Academy of Allergology and Clinical Immunology conference, Berlin.

The World Health Organisation's guidelines “Allergic rhinitis and its impact on asthma” were also launched at the conference. In a press release, Professor Jean Bousquet, University of Montpellier, said: “It is our hope that these new treatment guidelines will help to address the link between allergic rhinitis and asthma, both in terms of diagnosis and in a combined approach to the treatment of both diseases.”

Effective prevention of chronic kidney transplant rejection

New trial results suggest that tacrolimus (Prograf) and the Neoral formulation of ciclosporin are better at preventing long-term rejection of transplanted kidneys than the older Sandimmune preparation.

The results were presented at Transplant 2001, the annual meeting of the American Society of Transplantation, in Chicago on May 14 by Professor Herwig-Ulf Meier-Kriesche and Professor Bruce Kaplan, from the University of Michigan Medical School.

The study looked at the incidence of chronic allograft failure (ie, rejection of the kidney) four years post-transplant in 29,786 people, who were given Sandimmune, Neoral or tacrolimus. They found that the relative risk of chronic allograft failure in patients who received Neoral and tacrolimus was significantly lower than that of patients given Sandimmune. Compared with Sandimmune, the relative risk figures for Neoral were 0.60 (95 per cent confidence interval [CI] 0.53�0.67) and 0.68 (CI 0.56�0.81) for tacrolimus.

The authors comment: “This data, along with prospective trials demonstrating decreased acute rejection rates with both agents, offers strong advocacy for their use as opposed to Sandimmune.”

APBI report warns that UK could lose its leading role in genomics research

If the use of new medicines in the United Kingdom is not encouraged, then the research, development and manufacture of these products will be carried out elsewhere, according to a report published this week by the Association of the British Pharmaceutical Industry.

The report states that the UK is a world leader in the genomic revolution but that this is highly dependent on the relationship between the National Health Service and the pharmaceutical industry. It goes on to describe the progress made in the field of genomics and the challenges faced by both the NHS and British pharmaceutical industry.

Commenting on genomics research, Professor Tony Moffat, chief scientist, Royal Pharmaceutical Society, said: “A better knowledge of genomics will help us individualise medicines for patients, so that they are both safer and effective. As a profession, we must ensure that pharmacy plays its proper role in the new methods for prescribing and delivery of medicines.”

Raising the profile of indigestion

A leaflet intended to raise awareness of the causes, symptoms and types of indigestion, and to help people visiting a pharmacy to describe their symptoms properly, has been launched.

The leaflet is part of a campaign that arose after a survey conducted by the CHIC (Consumer Health Information Centre) showed that few people understand the cause of heartburn (of those surveyed, 19 per cent thought that heartburn was caused by acid around the heart). The campaign aims “to help people suffering from heartburn to communicate their symptoms more effectively when consulting a health professional such as a pharmacist... It is also designed to remind people about the valuable role that the pharmacist plays, and emphasise that over-the-counter remedies are an effective and safe way of helping yourself feel better”, says the CHIC.

“A guide to treating the symptoms of indigestion” has been produced by the CHIC in collaboration with the Royal Pharmaceutical Society and National Pharmaceutical Association. It can be obtained free from Consumer Health Information Centre, PO Box 16382, London WC1A 2QB, or by telephoning 020 7404 7842.

Alzheimer's disease linked to low vitamin levels

Low levels of vitamin B₁₂ or folate might predispose people to developing Alzheimer's disease (AD), researchers suggest.

A Swedish study assessed the incidence of AD in 370 people aged 75 years and older who were not taking supplements of vitamin B₁₂ or folate. After three years, people with low levels of either vitamin had twice the risk of developing AD (relative risk 2.1, 95 per cent confidence interval 1.2�3.5) compared with people with normal levels. A similar risk was found for people with low levels of both vitamins.

The researchers conclude that vitamin B₁₂ and folate may be involved in the development of AD. Previous studies had found that older people had low levels of vitamin B₁₂ and folate, and that vitamin deficiency might be linked with neurological disorders. The researchers suggest that vitamin B₁₂ and folate might lead to the development of AD by increasing levels of homocysteine, which has a neurotoxic effect (Neurology 2001:56:1188).