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Prescribing Advice for GPs

An NHS Prescribing Advisers' Blog

Chlorpromazine Stock Problems

Some oral dosage forms of Largactil® (Chlorpromazine) have been discontinued by the manufacturer for commercial reasons. 10mg tablets, 100mg tablets and the Forte Suspension (100mg/5ml) have all been discontinued.

The largest problem appears to be affecting the 10mg tablets; there is no generic version of this product widely available. 100mg tablets and oral syrup available in 25mg/5ml and 100mg/5ml strengths remain available as generic products.

Action: Patients who are being prescribed chlorpromazine 10mg tablets should be identified and have their treatment reviewed.

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Bowel Cancer drug review unpopular

The BBC has reported that several charities have criticised a decision not to make two anti-cancer drugs available on the NHS.

Bevacizumab (Avastin®) and Cetuximab (Erbitux®) have been appraised by NICE for use in metastatic colorectal cancer. NICE has recently made a final appraisal determination (FAD) available and while the process consultees can lodge an appeal is unlikely to change before publication.

The FAD recommends that these drugs are not used as they are not cost-effective. NICE has based their decision upon the cost to the NHS to improve the quality of life of a patient with metastatic colorectal cancer. NICE currently use a benchmark of £30,000 per Quality-adjusted life-year (QALY). Neither of these drugs meets that benchmark and in some prediction models are the cost per QALY was more than 3 times the NICE benchmark.

Action: Clinicians may wish to be aware of this information as patients may ask questions following media coverage.

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Smoking and risk of MI

An international study published in The Lancet has examined the link between tobacco use (smoking and chewing) and the risk of myocardial infarction (MI).

The case control study involved just over 27,000 patients in 52 countries and collected data on assessed the relationship between risk of acute MI and current or former smoking, type of tobacco used, amount smoked, effect of smokeless tobacco and passive smoking. Adjustments were made for differences in lifestyles between smokers and non-smokers.

The study found that current smokers were approximately 3 times as likely to experience an MI compared to non-smokers; the risk also increased by 5.6% for each additional cigarette smoked. [Odds Ratio 2.95 CI 2.77-3.14] This excess risk fell to 1.87 [CI 1.55-2.24] within 3 years of stopping smoking and to 1.22 [CI 1.09-1.37] after 20 years. Even after 20 years the remaining excess risk was statistically significant.

Action: All forms of tobacco usage should be strongly discouraged in order to prevent cardiovascular diseases.

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DTB review oral antibiotics for acne

The Drugs and Therapeutics Bulletin (DTB) has reviewed the use of oral antibiotics for moderate to severe acne. The review has also been reported in the Guardian newspaper.

The DTB review found that the NHS spent £9.3 million on minocycline last year although it is likely that a proportion of this was not for patients with acne. The same volume of doxycycline would have cost £3.9 million, a saving of £5.4 million.

Clinical Evidence has reviewed this are and found that there is a trade off between harms and benefits for all the tetracycline antibiotics.

The BNF recommends that oral antibiotic therapy should be reserved for second line when topical treatment is not adequately effective or is inappropriate.

Action: Topical treatment is first line for moderate to severe acne. Where oral treatment is necessary, a cost effective option (e.g. doxycycline) should be used and the patient warned about the potential harms.

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Atorvastatin in Stroke

The New England Journal of Medicine has published a study examining the effect of atorvastatin (Lipitor®) on strokes and transient ischaemic attacks (TIAs). The publication of this study has been reported in The Times and the Telegraph newspapers.

The study recruited approximately 4,700 patients who had experienced a stroke between 1 and 6 months prior to randomisation to receive either atorvastatin 80mg or placebo. Follow up was for 5 years and data were collected on fatal and non-fatal stroke, TIAs, cardiovascular events and deaths.

Statistically, there were fewer strokes in the active arm of the study with a reported absolute risk reduction of 2.2%. There was no difference in overall mortality between the groups. There was also an increased risk of haemorrhagic stroke in the active arm.

Journal Watch has appraised the study and noted that the study just achieved statistical significance. Since this is the first study to directly examine the effects of statins on strokes they concluded that it is unclear "whether an 80-mg dose of atorvastatin is necessary to achieve secondary prevention of stroke".

Action: Patients who have already had a stroke should be prescribed a statin as per formulary recommendations to prevent further atherothrombotic events.

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