- TARA PV
WHAT LESSONS HAVE WE LEARNED FROM ASPIRIN?
It is now 125 years since Bayer scientists, principally Felix Hoffman, first synthesised acetylsalicylic acid. Hoffman hoped to find an analgesic for joint pain that avoided the side effects of currently available therapy, principally opiate based. Aspirin is still widely used in rheumatology to the present day. But, in a lesson to those in pharmacovigilance, it was not until 1938 that a dentist reported the association between aspirin and gastric bleeding. Further studies showed that this apparently undesirable event was not purely a local irritant effect but was linked to the antiplatelet activity of the drug.
This led to a rapid interest in a potential new role for aspirin in preventing further episodes in patients who had suffered a stroke, a transient ischaemic attack or a myocardial infarct. However it was not until 1984 that the first randomized study showing the effectiveness of aspirin in secondary prevention after myocardial infarction was published in 1974 in The New England Journal of Medicine. In 1980, aspirin was approved by the US Food and Drug Administration for the secondary prevention of stroke and in 1984 for secondary prevention after myocardial infarction. Aspirin, having been largely usurped in the mid -20th century by paracetamol, ibuprofen and similar non-steroidal anti-inflammatory agents is now one of the most widely used medications in the world.
Such a classic repurposing of an old drug is nothing new, and has been a popular way for companies to extend the life cycle of their products. It has the advantage that most of the pre-clinical development has been undertaken and there is usually a large body of clinical experience allowing us to judge potential safety in the new indication. It remains important that monitoring of even a drug as widely used as aspirin must be continued in new indications without the presumption that the adverse event profile will be unchanged.
Other classic examples of repurposing include minoxidil and sildenafil. Minoxidil was originally developed and marketed as a third line antihypertensive, but its usefulness was limited by the side effect of excessive hair growth, a particular issue for women patients. The observation that minoxidil was associated with hirsutism led the originating company to develop topical formulations which have been marketed world-wide for the treatment of baldness. Sildenafil is another classic example of a side effect becoming the major marketing area. Although developed as a vasodilator for the treatment of hypertension and angina, during the initial investigations it rapidly became apparent that the vasodilatory effects were marked in men by the promotion of penile erections. In the patent lifetime of sildenafil, when marketed as Viagra for the treatment of erectile dysfunction, total sales exceeded $30 billion!
We can all think of other examples of side effects or serendipitous findings having a positive effect on the uptake of products, sales and profits. This should encourage to view pharmacovigilance as not being purely to look for the bad, but possibly to help us identify the beneficial.