Latest news and product developments

The latest analysis of the RCGP oral contraception (OC) study suggests that oral contraceptives may be associated with an overall reduction in the risk of cancer (Br Med J online: 11 September 2007; doi:10.1136/bmj.39289. 649410.55).

The cohort of 46 000 women provided 744 000 woman‐years for ever use of an oral contraceptive and 339 000 woman‐years of never use. Longer use was associated with increasing risks of cervical (RR 2.73), and pituitary or CNS (RR 5.51) cancers, but decreasing risks of uterine (RR 0.57) and ovarian (RR 0.38) cancers. OC use was also associated with a lower overall risk of colorectal cancers. The overall risk of any cancer was reduced by 12 per cent (RR 0.88).

Two‐year data revealed at the 29th Congress of the Société Internationale d'Urologie in Paris in September show that dutasteride (Avodart) and tamsulosin combination therapy provides significantly improved symptom control in BPH compared with either therapy alone.

The Combination therapy with Avodart (dutasteride) and tamsulosin (CombAT) study took over 4800 eligible men (age ≥50 years with a prostate volume ≥30cc, serum PSA level ≥1.5‐10ng per ml and IPSS ≥12) who received placebo for four weeks before being randomised in a 1:1:1 ratio to either dutasteride monotherapy (0.5mg per day), tamsulosin monotherapy (0.4mg per day) or a combination of both drugs.

At two years the primary efficacy end‐point was achieved: combination therapy was significantly more effective than either monotherapy, and continuous improvement could be observed throughout the two years. The combination therapy was also well tolerated, although drug‐related adverse events were more common with combination therapy (24 per cent) than either monotherapy (dutasteride 18 per cent, tamsulosin 14 per cent).

Dutasteride, a 5‐α reductase inhibitor, has been shown to be more effective for long‐term use in men than tamsulosin, while tamsulosin, an alpha blocker, has been shown to be effective in the short term. CombAT is the first study to demonstrate that the combination therapy of both drugs could lead to greater symptom improvement over time than an alpha blocker alone.

Novartis has introduced aliskiren (Rasilez), the first direct renin inhibitor for the treatment of hypertension. It is likely to be used in combination with other agents but is also licensed as monotherapy. The commonest adverse effect is diarrhoea.

At the recommended dose of 150‐300mg per day, a month's treatment costs £19.80‐£23.80.

The balance of benefit and risks from HRT may be more favourable for younger women, the MHRA says in its monthly bulletin, Drug Update (September 2007).

GPs considering prescribing HRT should evaluate the potential risks and benefits for each individual, the MHRA says. The bulletin summarises the risks of cardiovascular events and cancers associated with HRT.

Cardiovascular risk is a particular concern for women over 60, whose baseline risk is high; although evidence for the safety of HRT in younger women is limited, their baseline risk is lower.

Overall, the lowest dose of HRT should be used for the shortest possible time, and HRT should be prescribed to prevent osteoporosis only when alternatives are not suitable.

The MHRA also advises in the bulletin that:

• Individual risk of stroke, breast cancer and endometrial cancer should be considered before prescribing tibolone (Livial).

• Nasal formulations of desmopressin are no longer indicated for primary nocturnal enuresis; prescribers are reminded to adhere to product guidance on fluid intake.

• Patients and carers should be warned of the risk of psychiatric effects associated with corticosteroids; symptoms may develop within a few days or weeks in children and adults, and may be more common at higher doses. Patients taking steroids for more than three weeks are reminded not to stop treatment abruptly.

A list of questions and answers for patients is available at www.mhra.gov.uk.

• The use of parenteral B vitamins plus ascorbic acid (Pabrinex) may rarely be associated with severe allergic reactions, but this should not preclude its use for patients who need it.

Switching patients from atorvastatin (Lipitor) to simvastatin may increase the risk of cardiovascular events, according to a UK study presented at the European Society of Cardiology Congress in Vienna.

The analysis, from The Health Improvement Network database, included 11 520 patients taking atorvastatin for at least six months, of whom 2511 were switched to simvastatin.

Switching was associated with a 30 per cent increase in the relative risk of cardiovascular events, though absolute figures have not been reported. Patients who were switched were also more likely to discontinue treatment (21 vs 8 per cent of those continuing atorvastatin).

Details of the conduct of the study, which will be published in the British Journal of Cardiology, are not available.

New systematic reviews have fuelled the controversy over the cardiac safety of rosiglitazone and pioglitazone.

A meta‐analysis of four trials involving 14 291 patients and lasting one to four years found that rosiglitazone was associated with a significantly increased risk of myocardial infarction (relative risk, RR, 1.42) and heart failure (RR 2.09) but not cardiovascular mortality (RR 0.90) (J Am Med Assoc 2007;298:1189‐95).

The second review included 19 trials of pioglitazone involving 16 390 patients, with follow‐up from four months to 3.5 years.

Pioglitazone was associated with a lower risk of composite events (death, myocardial infarction, stroke; hazard ratio, HR, 0.82) but an increased risk of serious heart failure (HR 1.41) (J Am Med Assoc 2007;298: 1180‐8).

Neither review reported significant heterogeneity between the included studies.

Another systematic review of eight controlled and cohort studies concluded that metformin is the only antidiabetic drug not associated with an increased risk of harm in patients with diabetes and heart failure (Br Med J Online First 30 August; doi:10.1136/bmj.39314. 620174.80). The Canadian authors found methodological problems with all studies, and concluded that results for sulphonylureas were conflicting due to differences between the studies.

Health professionals need more education about rational prescribing for children with asthma, say researchers from Australia (Arch Dis Child online: 4 September 2007; doi: 10. 1136/adc.2007.119834).

Analysing trends in asthma medication prescriptions for children in the UK between 2000 and 2006, they found the proportion of steroid inhalers prescribed as combinations increased from 2.7 per cent in 2000 to 25 per cent in 2006.

The authors say this excessive increase is inconsistent with guidance that steroid‐only inhalers should be the mainstay for most people with asthma. Copyright © 2007 Wiley Interface Ltd