SIMVASTATIN

Reclassification process

  The proposal from Johnson & Johnson MSD Consumer Pharmaceuticals for the pharmacy availability of simvastatin 10 mg (Zocor Heart-Pro) was first considered by members of the Committee on Safety of Medicines (CSM) at a clarification meeting in September 2003 and again at a CSM meeting in October 2003. In light of discussions, CSM then advised that consultation could take place to seek views on the pharmacy availability of Zocor Heart-Pro.

  On 17 November 2003 the MHRA started a consultation exercise with a deadline for comments of 16 January 2004. The consultation document (ARM 18) and the outcome of the consultation exercise are displayed on the MHRA's website (www.mhra.gov.uk). One hundred responses were received expressing a wide variety of views on the proposed reclassification. Overall, about two thirds of respondents were in favour of the proposal. The responses received were then referred to the CSM for advice. No new issues were raised in the responses and CSM advised Ministers that simvastatin 10 mg could be safely sold under the supervision of a pharmacist without a prescription.

Safety assessment

  Patient safety is the prime consideration in any decision to make a medicine available over the counter (OTC). It is assessed against strict criteria relating to its safety in the circumstances in which it will be used. Simvastatin has been available in the UK since 1989 and many millions of patients have been safely treated. All medicines have the potential to cause side effects. Most of these side effects are not serious and are predictable from the known actions of the drug. During the use of simvastatin in clinical practice, there have been reports of reactions suspected to be associated with the medicine. As with all statins, simvastatin has been associated with some rare reports of severe muscle damage. The incidence of muscle damage with simvastatin is dose dependent and is more likely to occur at higher doses or when simvastatin is taken with other cholesterol lowering drugs. As the pharmacy medicine contains low dose simvastatin (10 mg) the risk of muscle damage is very small. This is a rare side effect and clear unambiguous advice is in the product information, patient information and information for pharmacists.

Efficacy of simvastatin

  There is a wealth of evidence to support the concept that lowering cholesterol is beneficial and reduces the risk of Coronary Heart Disease (CHD). Similarly there is a wealth of evidence that statins lower cholesterol levels and hence reduce the risk of CHD. The amount by which statins lower cholesterol is dose related, with higher doses resulting in greater absolute reduction. Simvastatin 10 mg has been shown to lower cholesterol levels, however, because the benefit is most demonstrable in patients at higher risk, large scale clinical trials of statins (including simvastatin) have generally targeted high risk patients. The latest research, however, provides good evidence to support the switching of statins to reduce the risk of a first major coronary event in people likely to be at a moderate risk of CHD.

  Numerous endpoint studies with statins confirm that lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of developing CHD. Simvastatin 10 mg produces around a 27% fall in LDL-C or 1.31mmol/l in absolute terms (standardising to a mean starting level in studies of 4.8 mmol/l). Reductions of this order reduce the risk of a major coronary event (CHD death or non-fatal myocardial infarction) by about one third after three years of treatment. The level of absolute risk reduction depends on the starting level of risk. Whilst no specific clinical trials have been conducted with simvastatin 10 mg in this particular patient population, it is reasonable to assume that these benefits would also apply to this group of people given that the effect of lowering LDL-C by simvastatin is consistent between populations, and the relation of LDL-C to risk is linear.

  In the self-medication population selected on the basis of age and sex and risk factor status (smoking, family history of early CHD, overweight or truncal obesity and ethnicity), starting 10-year CHD risk is likely to be in the range of 10-15%. Treatment with simvastatin 10 mg in this population will, therefore, produce a valuable reduction in risk, provided people are compliant with the treatment regimen; coupled with diet and lifestyle changes, the benefits to these individuals will be considerable. It is recognised that there are uncertainties about the effect of taking a statin on compliance with behavioural risk-modifications (such as healthy eating, exercise and smoking cessation).

CONCLUSIONPreventing CHD is a national priority. The National Service Framework for CHD sets out plans to ensure that the best care, in terms of prevention, diagnosis and treatment, is available to everyone. The NSF has prioritised those individuals at greatest risk. Making simvastatin available OTC provides a choice to those at moderate risk of CHD to access a preventative medicine they would not otherwise get on prescription.