12th August 2009
Recently, a number of generic versions of clopidogrel (as either the hydrochloride or besilate salt) have been introduced to the UK market. The existing branded product, Plavix® is based on the hydrogen sulphate salt. There are differences between the generics and Plavix in the indications for which the products are marketed.
Prescribers, pharmacists and medicines management teams need to consider carefully the issues relating to the introduction of generic clopidogrel. It is likely that the cost of generic clopidogrel will become lower than the branded product over the next few months and the potential savings on the drugs bill should be obtained for the licensed indications.
Leadership to develop local policies for off-label use of generic clopidogrel will be required and the major issues for consideration are presented in this blog. Some localities may, after considering the issues with local clinicians, decide that generic prescribing of clopidogrel off-licence may be their preferred policy. Others may wish to postpone a decision, and await further information or advise prescribing for this product only within licence.
What is the background to this?
Recently, a number of generic versions of clopidogrel (based on the hydrochloride, besilate or hydrogen sulphate salt) have received a Positive Opinion/licence from either the EMEA or the MHRA and several have been launched in the UK. The generics available in the UK are based on either the hydrochloride or besilate salt and are marketed for the prevention of atherothrombotic events in patients suffering from myocardial infarction, ischaemic stroke or established peripheral arterial disease but not for use in acute coronary syndrome (ACS).
Plavix (clopidogrel hydrogen sulphate) is the only marketed clopidogrel available in the UK for prevention of atherothrombotic events in both patients suffering from ischaemic disease and those suffering from ACS.
Information from Primary Care Trusts suggests that sanofi-aventis (the manufacturer of Plavix) are advising prescribers, pharmacists and practice managers that Plavix is the only clopidogrel-containing preparation available to treat ACS. Should prescribers wish to ensure that Plavix is dispensed when clopidogrel is prescribed for the treatment of ACS, the company advise that they prescribe by brand name or mention clopidogrel hydrogen sulphate on the prescription.
Why are the generic preparations not marketed for ACS in the UK?
As we understand it, this may be because there are patents in force which preclude the generic manufacturers from including on the SPC the use of clopidogrel with aspirin in ACS.
The EMEA has granted a Positive Opinion to more than 20 generic clopidogrel products, of which eight are for both indications i.e. ischaemic disease and ACS. Both the besilate and hydrogen sulphate salts are represented amongst those eight generics. However, if a generic manufacturer obtains a licence for an indication which is still protected by a patent they cannot market the product in those countries where the patent is active. Both generic clopidogrel BMS and clopidogrel Winthrop (sanofi) received market authorisations in 2008 for both indications.
Patent issues are a complex area and if further relevant information becomes available we will provide an update.
What issues require consideration?
The major issue relates to responsibilities of the prescriber and dispenser of medicines which are outside the product licence. Health care professionals face this situation many times each working day.
Generally speaking, in off-label use, the prescriber and dispenser may acquire greater legal responsibility for the use of a medicine, whereas when prescribing is within the licence the responsibilities are shared between the medicines manufacturer and the prescriber, and sometimes the dispenser. This does not prevent much off-label prescribing when the practice is well established. Indeed, much prescribing for children falls into this category.
In this instance, prescribers and those responsible for advising on local prescribing policies will need to ensure that all potential savings on the drugs bill are obtained following the availability of generic clopidogrel. When clopidogrel is prescribed for one of the indications for which the generic products are licensed, generic use should rapidly become local policy.
When prescribing of clopidogrel is for an indication which is outside the licensed indications of generic clopidogrel local prescribers and prescribing managers will have to consider whether they feel that using one of the generic clopidogrel products off-label is reasonable. In such considerations they may wish to examine the level of risk of using a generic product (which has been granted a licence and is therefore considered to have a reasonable balance of efficacy and safety for myocardial infarction, stroke or peripheral vascular disease) in people with acute coronary syndrome. These are all conditions affecting patients with many similar characteristics and which have similar pathological processes.
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