GPs have been warned to assess renal function before prescribing the new anticoagulant drug dabigatran and not to give it to patients with severe renal impairment.
The warning follows 12 fatal haemorrhages among elderly patients in Japan who were given the drug. In six cases, the patients had severe renal impairment and the drug was prescribed off-label. The EMEA records 256 fatal haemorrhaging case reports worldwide.
Pulse has learnt that the MHRA is to issue advice on dabigatran in the December issue of its drug safety update, after the manufacturer Boehringer Ingelheim sent to UK prescribers in October saying the drug's prescribing guide and product information summary will be amended.
In advice endorsed by the EMEA's Committee for Medicinal Products for Human Use, Boehringer Ingelheim said GPs should assess patients for renal impairment prior to therapy and exclude any patients with creatinine clearance levels of under 30 ml/minute.
They also said that while on the drug, patients over 75 should have their renal function reassessed annually, and patients at risk of deterioration of renal function should also undergo reassessments, says the company.
Dabigatran is licensed in the EU for the prevention of venous thromboembolism in patients who have undergone total knee or hip replacements, and for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
The EMEA's Committee for Medicinal Products for Human Use will discuss any further developments at a meeting next week, and reports a total of 256 spontanenous case reports of fatal haemorrhaging associated with the dabigatran on their EudraVigilance database, including 21 in the EU.
The agency says this must be seen in the context of increased use and awareness of the drug, which leads to higher than usual side effects.
Professor David Fitzmaurice, a GP in Birmingham and chair of the Primary Care Cardiovascular Society's anticoagulation working group, said: ‘These patients should have renal function assessment anyway, irrespective of the anticoagulant being used.'
‘The issue in Japan was that they did not understand that dabigatran is a powerful anticoagulant and were using inappropriate dosing regimes because of their lack of understanding of how the drug works.'
‘My understanding is that eGFR will be used [for assessment], which is routine now anyway.'
Boehringer Ingelheim's medical director Dr Charles de Wet told Pulse the changes would strengthen the advice about renal function that was given in the original European product information.
‘The original product information does say that one should look at renal function, but it wasn't upfront. One would have thought that most practising physicians would have done this already, but it became clear that physicians didn't always look at renal failure.'
Dabigatran is licensed for patients with severe renal impairment in the US, albeit at a lower dose. Dr de Wet said that this dosage was not in the original study, but was included in the licence at the request of the US Food and Drug Administration.