The Pharmaceutical Journal Vol 265 No 7126 p860-862
December 09, 2000 Articles

The impact of amfebutamone (bupropion) on National Health Service smoking cessation services

By Ann McNeill and Miriam Armstrong

The pharmacy plan for England highlights the role of the pharmacist in smoking cessation. In June, 2000, amfebutamone (bupropion) hydrochloride - marketed as Zyban - was licensed for smoking cessation as a prescription only medicine available on the National Health Service. The likely impact of amfebutamone and its effect on the new NHS smoking cessation services are discussed in this article, as are the implications for the pharmacist's role in smoking interventions. The article builds on new smoking cessation guidance to pharmacies sent out recently by the Pharmacy Healthcare Scheme and on the original and updated evidence-based smoking cessation guidelines. Although this article relates largely to England, it will be relevant for other parts of the United Kingdom

In June, 2000, the Medicines Control Agency granted a licence for amfebutamone (bupropion) hydrochloride - marketed by Glaxo Wellcome as Zyban - as a prescription only medicine to be used for smoking cessation (with motivational support) in the United Kingdom. This is an exciting development because amfebutamone, originally developed as an antidepressant in the United States, is the first new type of pharmacological treatment to be licensed since the first nicotine replacement therapy (NRT) was introduced into the market in 1981.
The Department of Health also announced that amfebutamone would be available on NHS prescription,¹ unlike the majority of nicotine replacement therapies then on the market which were "blacklisted ". However, the Secretary of State for Health has recently announced that it proposes to make NRT available on NHS
prescription² following a process of consultation. Furthermore, the Committee on Safety of Medicines is being asked to consider whether NRT can also be made available for general sale.
Public health groups have called for access to NRT to be widened, so that NRT can be made available on the NHS³ as well as being available through pharmacies and on general sale.^4,5 All routes are effective and there is an ethical argument that cigarettes should not be more widely available than NRT.
The use of NRT in smoking cessation has been demonstrated to be highly cost effective.⁵ It was recently estimated that the cost per discounted life year saved from a societal perspective, ranged from £212 (brief advice) to £873 (an integrated smoking cessation service involving brief advice, self-help, NRT and specialist cessation service). These figures compare very favourably with most health care procedures; for example, a recent international review found the median societal cost of over 310 medical interventions to be £17,000 per life year gained. Given that amfebutamone has a similar cost and efficacy pattern (see below) to NRT, it will also be a very cost-effective treatment.

What is amfebutamone and how effective is it?

Amfebutamone was originally developed as an atypical antidepressant having central dopaminergic and adrenergic actions. To date, there have been four trials^6–9 (two fully published) that have clearly demonstrated the efficacy of amfebutamone in smoking cessation. Its exact mechanism of action is unknown as the drug works equally well in smokers with and without a past history of depression.
Amfebutamone will clearly have an impact on smoking cessation in the UK. However, some of the media coverage promoting a 30 per cent success rate and amfebutamone being twice as effective as NRT should be interpreted cautiously for the following reasons:

• The trials so far have been carried out in the US with frequent behavioural counselling sessions being offered alongside the drug. The effectiveness has not yet been tested on a real-life basis in primary care.
• The 30 per cent success rate is a "point " prevalence rate of abstinence emanating from one of the studies⁹ which compared amfebutamone, placebo, a nicotine patch and a combination of amfebutamone and the nicotine patch. The more widely used and more stringent "continuous " abstinence rates through one year of follow up were 5.6 per cent with placebo, 9.8 per cent with the nicotine patch, 18.4 per cent with amfebutamone alone, and 22.5 per cent with combined amfebutamone/nicotine patch.
• This same study therefore demonstrated that amfebutamone alone was significantly more effective than placebo or the nicotine patch but there was no statistically significant difference between amfebutamone and the combination of amfebutamone with nicotine patch. These findings have been interpreted as amfebutamone being twice as effective as NRT, but a recent review¹⁰ cautioned against making any comparison on the basis of one study and encouraged further comparative studies. In addition, this study only compared amfebutamone with the patch and not other forms of NRT. Further research is also needed to elucidate whether the combination of amfebutamone and NRT is more effective than either treatment alone.

Whom should amfebutamone be prescribed for?

The product information¹¹ emphasises that only smokers motivated to quit should be prescribed amfebutamone. Treatment differs from treatment with NRT¹² as the patient starts amfebutamone treatment while still smoking and sets a target quit date within the first two weeks. The recommended initial dose (150mg to be taken daily for three days, increasing to 150mg twice daily) should not be exceeded because amfebutamone is associated with a dose-related risk of seizure (a rate of 0.1 per cent at doses up to the maximum recommended daily dose). There has been negative publicity recently about seizure risk with amfebutamone¹³ and cancer risk with NRT.¹⁴ On the first, the risk of seizures still appears to be within a 0.1 per cent risk and this is broadly similar to other antidepressants. The publicity on NRT and cancer originated from an in vitro study suggesting that some metabolites of nicotine from cigarette smoke can be transformed into nitrosamines. There is no evidence of this happening in people using NRT. Undesirable effects of amfebutamone may also be observed, the most notable being dry mouth and insomnia.
Amfebutamone should not be used by pregnant or breast-feeding women and is not recommended for use by young people under 18 years of age. It is contraindicated in patients with certain conditions, including epilepsy, eating disorders and severe liver disease.¹² There are drug interactions with theophylline, tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, antipsychotics, beta-blockers, class 1c antiarrhythmics, enzyme inducers and inhibitors, orphenadrine, cyclophosphamide and levodopa.¹³
Prescribing information indicates that patients should be treated for seven to nine weeks with a review at seven weeks, when the treatment should be discontinued if no effect is seen. A pack of Zyban contains 60 tablets, 10 per blister strip. This would constitute just over four weeks' supply at a basic price of £42.85. On cost-efficacy grounds, it may be preferable to supply one pack initially (lasting four weeks) followed by the remainder of the course (another four weeks) if the patient wishes to continue and the therapy is having an effect.⁵
Patients using Zyban will be able to access a Glaxo Wellcome sponsored support programme - "The right time programme " - which includes a starter pack containing various motivational materials, mailings at key time points and the facility to use a free telephone service run by dedicated counsellors.

How does amfebutamone fit within the Government's new smoking cessation services?

In December, 1998, the Government launched its first ever White Paper on smoking, "Smoking kills ".¹⁵ This outlined a comprehensive strategy involving, among other things, a tobacco advertising ban, regular increases in the price of tobacco, increasing controls on smuggling, increasing smoke-free places, a public education campaign (launched in December, 1999, with the strap line "Don't give up giving up ") and new NHS smoking cessation services to help smokers wanting to stop. These services were developed in health action zones in year 1 (1999-2000) and then throughout health authorities in England in year 2 (2000-01). The budget in year 1 was £10m and this was increased to £20m in year 2.
Guidance issued to health authorities¹⁶ identified three levels of smoking cessation service:

• Brief interventions - made opportunistically during routine consultations by any health professional.
• Intermediate services - one to one counselling, for example, as provided by some pharmacies and GP practices. Health professionals delivering these interventions could be reimbursed provided they had been trained, were registered with the local smoking cessation co-ordinator and were willing to follow up patients and fill out forms necessary for the monitoring of the services.
• Specialist clinics - where smokers could be treated either individually or in groups. Again professionals could be reimbursed for providing these, if they met criteria similar to those specified above for the intermediate interventions.

The amount of reimbursement differs between health authorities throughout England. At any of the three levels a smoker could be introduced to the concept of either NRT or amfebutamone as a cessation aid. Both are proven effective aids to a successful attempt to stop smoking and as such are considered to be an integral part of the new NHS smoking cessation services.
Before amfebutamone was granted a licence, nicotine replacement therapies were the only pharmacotherapies considered effective as smoking cessation aids. At the time of publication of the White Paper, as the majority of NRT products were not available on NHS reimbursable prescriptions, some provision was made by the Government to increase the accessibility of NRT to people on low incomes through a voucher system. Those offering intermediate or specialist support could offer one week's free supply of NRT (this has recently been increased to four to six weeks' free supply) to those smokers entitled to free prescriptions who were prepared to receive this support.
The launch of amfebutamone and the decision to prescribe it on the NHS has implications for the new smoking cessation services:
Brief opportunistic interventions Health professionals have been encouraged to take opportunities to advise smokers to stop during routine consultations. The advice should include the offer of support for those who need it and amfebutamone can now be included in the range of support that is currently available. At present, amfebutamone can only be prescribed by a doctor and smokers will have to make an initial visit to their GP to determine if the drug will be clinically appropriate for them.¹⁷ Pharmacists and other health professionals will not be able to supply amfebutamone unless patient group directions are set up by the health authority allowing them to supply under protocol. However, pharmacists offering intermediate interventions could be involved in the assessment of suitability for amfebutamone.
As the effectiveness of amfebutamone from existing trials is linked to frequent behavioural counselling sessions, the Department of Health has suggested that smokers receiving amfebutamone from their GPs could be directed to the specialist services for further support.¹⁷ As the likelihood of success in giving up improves with additional specialist support when using either NRT or amfebutamone, pharmacists should be able to provide further specialist support or be able to suggest other support services (see below).
Intermediate and specialist smoking cessation services As well as behavioural support, the intermediate and specialist smoking cessation services can now offer amfebutamone as an alternative to NRT.

The pharmacist's role in the new smoking cessation services

Pharmacists have been shown to play an important role in smoking cessation,^18–20 through their opportunistic contact with people who are in good health as well those who are ill, their ability to advise people about their smoking behaviour and their expert knowledge of the role that medicines can play in improving health and reducing illness.
Opportunistic advice Pharmacists should opportunistically ask customers if they smoke (there are many appropriate triggers such as customers purchasing cough medicines, smokers' toothpaste, pregnancy tests, folic acid, etc) and where appropriate offer advice to smokers to stop.²¹
Intermediate and specialist smoking cessation interventions The recently published updated smoking cessation guidelines²² highlight the role of the pharmacist in delivering intermediate and specialist smoking cessation interventions. By combining data from two recent randomised trials in the UK, the guidelines indicated a positive effect of a structured package of behavioural support and NRT provided by pharmacists, compared with unstructured care. Community pharmacy personnel therefore have the potential to make a significant contribution to national smoking cessation rates.²³
To be eligible to provide the intermediate and specialist levels of support in the new NHS smoking cessation services, the pharmacist must be appropriately trained and be approved by the local smoking cessation co-ordinator. Support should involve an initial consultation, with weekly follow-ups for the first month and then longer term follow-ups as appropriate for monitoring. The initial consultation will involve assessment of motivation and readiness to quit, agreement on a quit date and advice on and provision of NRT and/or amfebutamone (as appropriate).²⁴ Weekly support should be offered for the first month and the patient needs to be followed up at one month for monitoring feedback.
National voucher scheme Pharmacists also have a role to play through the voucher scheme. In June, 2000, a national framework agreement for the supply of NRT was agreed between the Department of Health and the major manufacturers of NRT products. Health authorities may decide to participate in this agreement or make their own arrangements for the supply of NRT. Under the terms of the framework agreement, health authorities can obtain retrospective rebates on the trade price of NRT products. Smokers entering the smoking cessation services who are eligible for the one week's supply of NRT are given vouchers which they can exchange for NRT products in participating pharmacies. The pharmacist retains the discretion to decide which product is most suitable for the patient. The pharmacist can only be reimbursed for the cost of the product on the submission to the health authority smoking cessation co-ordinator of a fully completed voucher.
Pharmacists can supply NRT products in exchange for vouchers, or continue selling any of the six nicotine replacement therapies currently available over the counter (gum, patch, nasal spray, inhaler, sublingual tablet, lozenge or nicotine nasal spray). A recent study which compared four of the NRT products found no differences in overall efficacy or effects on withdrawal discomfort. However, it is possible that products may be differentially effective for different target groups. Until this is known, other than where specified below, personal preferences should guide the choice. The pharmacist is ideally placed to help the customer choose the products that suit them best.
Guidance about amfebutamone Pharmacists, in their role as expert advisers on medicines, may be approached by smokers asking about amfebutamone and whether it is suitable for them. Alternatively they will sometimes need to assess suitability for NRT or amfebutamone as part of providing an intermediate level intervention.
Smokers should be advised about both amfebutamone and NRT as they have both been shown to be effective in smoking cessation and currently it is not known if either is superior. Neither is, however, a "magic bullet "; the smoker will still need strong motivation to quit. In both cases, smokers should be advised of the added value of obtaining support from the specialist smoking cessation services. Pharmacists could then give further specialist support or provide information on local services.
The following scenarios may be helpful in deciding what action to take:

• If the customer is interested in having amfebutamone then they need to be advised to visit their GP who will assess their suitability and, if appropriate, prescribe it. Customers who have been prescribed amfebutamone should be advised on the most appropriate way to take the product and of the increased chance of success if they receive ongoing motivational support.
• If the customer is interested in NRT or is not suitable for amfebutamone or does not want to visit the GP, then the offer of NRT should be made. If the customer has tried NRT but failed they may wish to try it again or try another type. They should be reminded of the need for an adequate dosing regimen and the recommended period (usually from eight to 12 weeks) and that ongoing support will increase their chances of success.
• Customers should be informed of the availability and types of services offered by specialist smoking cessation services.
• Customers should be encouraged to take leaflets on self-help advice from the pharmacy - for example, No Smoking Day leaflets offer practical support and solutions to problems faced by those trying to give up. Manufacturers' materials may also be of help.
• Customers can be advised of the NHS Smoking Helpline on 0800 169 0 169 or the NHS Pregnancy Smoking Helpline on 0800 169 9 169.

Conclusion