Neurologists have been warned of a looming shortage of the thrombolytic agent tenecteplase (Metalyse) because limited supplies are being used inappropriately in place of alteplase for the treatment of acute stroke.
Tenecteplase is being adopted with enthusiasm for the treatment of stroke because of its more convenient single bolus dosing compared to the infusion needed for alteplase, according stroke specialist Professor Mark Parsons of the Melbourne Brain Centre at the Royal Melbourne Hospital.
But the drug is not approved for thrombolysis in acute stroke as there is currently a lack of evidence from phase III trials to support its equivalence to alteplase, according to a commentary article in the MJA co-authored by Dr Aletta Schutte and Professor Christopher Levi of the University of NSW.
They note that tenecteplase is currently only approved for use in acute MI, but access to the drug for this indication is under threat because the thrombolytic is now being recommended by most state stroke expert committees and telestroke networks to be used as the sole thrombolytic for stroke.
And any shortage of tenectaplase would be of particular concern in rural Australia where it is the current emergency treatment for acute MI (often pre-hospital) in order to offer timely myocardial revascularisation, they warn.
In their article, the note that the only evidence for tenecteplase in stroke comes from phase II studies in patients with large vessel occlusion stroke, who account for only 20% or less of all thrombolysis-eligible stroke patients. These results should not be extrapolated to milder stroke and it is therefore inappropriate and irrational to be recommending tenecteplase outside of acute MI until phase III studies such as TASTE and ATTEST-2 have been completed, they argue.
With production of tenecteplase unable to be scaled up due to the complexity of its cell culture-based manufacturing process, it is crucial that limited stocks be reserved for use in acute MI, particularly during the pressures of the COVD-19 pandemic, the authors say.
“In the context of a potential shortage, coupled with the absence of high level evidence, convenience should not become a compelling reason to switch to tenecteplase for stroke,” they write.
“Furthermore, in Australia and other large countries, where rapid PPCI [Primary Percutaneous Coronary Intervention] access is limited by geographical constraints, pre-hospital and small hospital lysis programs currently exist for STEMI. These protocols solely use tenecteplase, meaning an interruption in supply would further disadvantage regional/rural patients, a population already suffering poorer cardiovascular outcomes.
They conclude that evidence and common sense dictate that there is no compelling reason to switch to tenecteplase for stroke, when Australia is facing a supply shortage of the drug.
“Difficult times typically call for rational decisions, and not for ‘premature translation’. This is yet another example of unintended consequences, despite the best of intentions, occurring during the COVID-19 pandemic.”