A global shortage of thrombolytic agent tenecteplase has prompted the Therapeutic Goods Administration (TGA) to extend the shelf-life of some batches and approve imports of alternative products.
Australia’s TGA last week warned low stocks of Boehringer Ingelheim’s tenecteplase (Metalyse) injection were expected to extend over the next 18 months.
It has therefore approved a submission from the manufacturer to add another 12 months to the effective life of the powder and pre-filled syringes, “to reduce wastage and maximise access to this essential medicine”.
The TGA said it had also approved the supply of overseas-registered equivalent products under an exemption granted in section 19A of the Therapeutic Goods Act 1989, “to minimise the public health impact of this shortage”.
Pro Pharmaceuticals Group said it would be supplying Canadian and US-registered TNKASE tenecteplase 50 mg powder for solution kit to Australia, for the indication of thrombolytic treatment of the acute phase of myocardial infarction (MI). However the company said the reconstitution of the s19A imported products registered and marketed by Roche Canada and Genentech may be different to Metalyse.
The TGA said that it was also working in collaboration with expert groups, which are developing clinical guidelines to assist healthcare professionals during the tenecteplase shortage.
Shortages of the thrombolytic were predicted in a 2020 article in the MJA, in which neurologists said the complex production process for tenecteplase created capacity limitations that meant it wasn’t possible to scale-up manufacturing to supply enough of the drug to meet increasing demand for use in both MI and stroke.
“This is because tenecteplase is recombinant technology produced by cell culture with a limited production. If this increased demand for tenecteplase outstrips its fixed supply, it will almost certainly lead to a period of tenecteplase being unavailable in Australia,” they warned.
The authors noted that tenecteplase was an attractive alternative to alteplase, particularly in regional areas as it could be given as a single injection rather than an infusion over several hours.
At that time they warned that increasing off label use of the drug for stroke may have flow-on effects for drug supply for patients with MI.
“Concerningly, recent proposals (that have accelerated during the COVID-19 crisis) to adopt tenecteplase as the recommended thrombolytic agent for stroke reperfusion will potentially limit access to tenecteplase for patients with acute MI,” the article said.
“This is of particular concern in rural Australia where tenecteplase is the current emergency treatment for acute MI (often pre-hospital) in order to offer timely myocardial revascularisation,” they wrote.
Professor Stephen Davis, Director of the Melbourne Brain Centre and a Royal Melbourne Hospital stroke specialist told the limbic that use of tenecteplase in stroke was likely continue to rise.
“There is a swing in the stroke world to preferring it over alteplase in some centres,” he said.
He pointed to new research from the Canadian AcT randomised trial of 1,600 patients eligible for thrombolysis showing the single-bolus injection was not inferior to alteplase — it was a “reasonable alternative” — and had similar safety profile.
Separately, the TASTE-A randomised trial conducted through the Melbourne Mobile Stroke Unit found tenecteplase resulted in superior early reperfusion when compared to alteplase.
“The situation now is that there is still one large Australian trial ongoing, so there is some degree of equipoise, but around the world there are quite a number of people using open-label tenecteplase,” he said.
“It’s a much easier drug to give than alteplase. It’s one vial, it’s quick, it’s easier and it looks just as good. Before thrombectomy, our studies showed it was better. There is a swing, which is affected by the current shortage, but people are still using it.”
In New Zealand, which has also been impacted by a shortage of tenecteplase, guidance drawn up by cardiologists, stroke neurologists and emergency medicine specialists advises clinicians that supplies of tenecteplase should be prioritised for out-of-hospital STEMI thrombolysis, including rural and remote facilities.
The advice, endorsed by CSANZ, recommends that alteplase be used as the thrombolytic of choice for STEMI in hospitals, and also as thrombolytic of choice for ischaemic stroke and massive pulmonary embolus.