It is more than 10 years since the MHRA advised that the decision to prescribe a NSAID should be based on an assessment of a patient’s individual risk factors, including any history of cardiovascular and gastrointestinal illness.
Those around at that time will remember the controversy surrounding the introduction and subsequent withdrawal of rofecoxib from the market.
The MHRA’s Drug Safety Update labels diclofenac as “having a thrombotic risk profile similar to that of at least one coxib (etoricoxib) and possibly others”. So, are all coxibs the same?
The most recent edition of the Palliative Care Formulary has thrown a curve ball with its recommendation to use celecoxib as the first-line NSAID in its patient cohort.
Looking back at the evidence base, we see the CLASS trial randomised nearly 8,000 patients to a supratherapeutic dose (400mg bd) of celecoxib or the maximum dose of ibuprofen (2,400mg) or diclofenac (150mg). The result was a similar number of cardiovascular events in the coxib and NSAID arms but fewer combined symptomatic ulcers or upper GI ulcer complications in the coxib group.
This was not, however, the end of the story. The trial authors were criticised for reporting six-month data only when data at 65 weeks appears to show no clear GI benefits. Also, the dose of celecoxib was not one likely to be used as it is way above BNF dose limits.
Following the withdrawal of rofecoxib, the FDA asked Pfizer (manufacturer of celecoxib) to perform a cardiovascular safety trial (PRECISION). Doses were reasonable (although the ibuprofen dose exceeds that recommended in the UK): celecoxib 100mg bd, ibuprofen 600mg tds and naproxen 375mg bd.
Celecoxib was shown to be non-inferior to ibuprofen and naproxen from a cardiovascular point of view and to have potential GI advantages. However, the study has been criticised for high rates of dropout and numerous indicators of poor efficacy in the celecoxib group.
So what should we prescribe? Waiting for national guidance is clearly appropriate but locally we are asking CCG leads whether individual prescribing by palliative specialists is likely to be questioned at practice level, and whether this use should be detailed within the formulary.
Given the potential for cost savings associated with celecoxib, it will be interesting to see if any areas incorporate it into their prescribing advice before any national recommendation.
Celecoxib 100mg bd = £1.75
Ibuprofen 400mg tds = £2.94
Naproxen 500mg GR bd = £4.16
This column is produced in association with the UKCPA. The views expressed are those of the author and are not necessarily those of either Pharmacy Magazine or the UKCPA. For more information about the UKCPA, access ukclinicalpharmacy.org