THE STATE’S drug regulatory body has warned doctors of a potential drug interaction that could put thousands of patients at risk of heart attack.
In its latest Drug Safety Newsletter, the Irish Medicines Board(IMB) told doctors here of its concern that people taking the anti-clotting drug clopidogrel (Plavix) in combination with a commonly prescribed range of acid suppressant drugs – proton pump inhibitors (PPIs) – are at risk of cardiac problems.
PPIs are used in the treatment of peptic ulcers and acid reflux conditions. Brands marketed in Ireland include Losec, Nexium, Protium and Zoton.
The warning comes following the publication of research in the Canadian Medical Association Journal which looked at more than 13,500 patients who were being treated with Plavix after they had an acute heart attack. It found increased rates of hospital readmission for subsequent cardiac events in people taking a PPI in combination with the anti-platelet drug compared with those not taking the combination.
The authors concluded that “concomitant treatment with clopidogrel and proton pump inhibitors should be minimised”.
“Healthcare professionals should re-evaluate the need for starting or continuing treatment with a PPI in patients taking clopidogrel,” the IMB advised doctors.
Commenting on the IMB’s warning, Dr Michael Barry, consultant clinical pharmacologist at St James’s hospital in Dublin, said, “It is an important issue to highlight as thousands of patients are on a combination of proton pump inhibitors and clopidogrel.
“We looked at hospital discharge prescriptions in 2008 and estimate that approximately 3,500 patients are discharged from our hospitals each year on the combination. Over two-thirds of such patients are 70 years or over.”
But he said the research paper had a number of important limitations including the absence of data on cardiac risk factors such as smoking, blood pressure and cholesterol levels between the two study groups.
“The potential impact of other drugs that are metabolised by cytochrome P450 enzymes, for example statins, was not considered.”
This is a reference to enzymes in the liver that clopidogrel and PPIs compete for and are the likely reason for the interaction between them.
“Things are further complicated as there are other publications that query whether the interaction is of clinical significance, [although] the basic science, in vitro studies do support the possibility of an interaction as all the proton pump inhibitors have the ability to inhibit the enzymes responsible for the activation of clopidogrel,” Dr Barry said.
The drug-prescribing expert said it was important to emphasise that all of the proton pump inhibitors have the potential to interact with clopidogrel.
“In practice, what clinicians may consider is substituting a histamine 2(H2) receptor antagonist like ranitidine for the PPI. Ranitidine would not be expected to interact with clopidogrel,” he concluded.