Global action is needed to counter the dangers of substandard life-saving drugs that are putting patients' lives and health at risk, according to heart specialists writing in the new (19 April) issue of Europe's leading cardiology journal, the European Heart Journal.
In an editorial , Drs Felicita Andreotti and Filippo Crea said that raising awareness that poor quality drugs exist may cause patients excessive worry, but lack of vigilance could generate distrust by consumers and professionals.
"It is essential to bring the issue to public attention as a first step in reinforcing surveillance," said Dr Andreotti of the Institute of Cardiology at the Catholic University Medical School in Rome, Italy.
The editorial was prompted by the findings of a German research team testing the quality of batches of streptokinase – a clot-busting (fibrinolytic) drug widely used in the emergency treatment of heart attacks.
Dr Peter Hermentin and his team from ZLB Behring GmbH in Marburg – one of the companies manufacturing streptokinase – tested 16 streptokinase preparations (21 samples) for the streptokinase activity, using a validated assay, and found that only three (including their own) matched the minimum fibrinolytic requirements of the European Pharmacopaeia, the European authority on quality and safety of medicines. The activity of the remainder varied from 86% of the claim on the label right down to just a fifth. European Pharmacopaeia demands activity of 90–111%. There were also differences in composition and purity.
Said Dr Hermentin: "The dose of fibrinolytic agents such as streptokinase must be carefully controlled to maximise therapeutic activity while avoiding adverse effects. Too low a dose won't restore blood flow in the artery and too high a dose could cause a bleed in the brain.
"While we analysed only one sample from most of the batches – albeit testing more than one vial and using two assays in most cases –and therefore can't generalise from our results, there are potentially serious clinical implications. The discrepancy between claimed and actual activity of many streptokinase preparations could cause life-threatening situations in severely ill patients."
Dr Andreotti said that streptokinase belonged to one of a few dozen contemporary groups of life-saving drugs and that it was used to treat one of the most common and suddenly fatal medical scenarios – acute myocardial infarction (heart attack). It ranked among the World Health Organization's essential medications and, like all fibrinolytics, there was a fine balance between efficacy in restoring blood flow to the heart and the risk of causing major bleeds. Strict calibration of the activity was mandatory and must be stated on the manufacturer's label.
"I found it astonishing that only three of the 21 formulations tested – 14.3% – were reported to meet the minimum requirements of the European Pharmacopoeia," she said.
"How can consumers and health professionals be sure that the drugs they use are safe and effective?" she queried. Regulatory approval was based on short and medium term safety and efficacy as demonstrated through clinical trials. But, once a drug reached the open market, systematic long-term evaluation was more difficult, with assessment relying on a combination of government-sponsored vigilance, spontaneous reports and epidemiological monitoring.
Present arrangements were not fully adequate and did not always favour impartial decisions, she said, relying, for instance, on withdrawal by the same agency that approved the initial marketing, or on reports by the manufacturers. Also, current post-marketing control to curb the making and trading of substandard or counterfeit medicines was insufficient.