Clinicians are being advised to conserve tenecteplase wherever possible as a global shortage of the thrombolytic agent extends to alteplase in some regions.

With tenecteplase stocks predicted to remain in short supply for at least the next 18 months, experts groups such as the Stroke Society and Stroke Foundation have released a TGA-backed list of recommended “conservation methods” for clinicians, saying supply “must be prioritised to settings where there are no alternatives”.

One of these settings is pre-hospital thrombolysis – usually in ambulance services.

The other is small rural and remote facilities, meaning metropolitan and larger regional hospitals should limit themselves to alteplase, it says (link).

The advice released on 25 August followed a meeting with stakeholder groups as well as a successful application by tenecteplase importer Boehringer Ingelheim to extend the expiry date on its Metalyse products by 12 months.

“The working group has agreed that usage of tenecteplase must be reduced by at least 35% nationally or stock will be exhausted in Australia by the end of 2022,” it said.

It came after authorities in the UK issued a national patient safety alert warning stocks were also running low on alteplase, with NHS trusts receiving only half their usual supply of both drugs.

Therefore, alteplase stock “should be conserved for patients with acute ischaemic stroke, given the lack of an alternative and the significant risk of harm without receipt of treatment,” the alert issued last week said (link).

The TGA did not follow suit on alteplase, but it did raise the possibility of further expiry date extensions for tenecteplase, saying any out-of-date batches should be set aside and not disposed of, pending further decisions.

It said the shortage was due to manufacturing capacity constraints following increases in global demand.

However, the regulator stopped short of restricting its use to approved indications, of which there is currently just one: thrombolytic treatment in the acute phase of MI.

This was despite being “aware of off-label use, particularly in areas/settings where access or ability to use alternative treatments is limited”.

Guidance is clear

Consultant neurologist Professor Bruce Campbell, the head of stroke at Royal Melbourne Hospital, said the drug had been in frequent use within Victoria and SA for stroke, but less so in some other locations.

He said he was aware of the alteplase supply issues overseas, but said it was the only alternative. Alteplase was administered via bolus and infusion over an hour compared to the 10 seconds required to give tenecteplase, he added.

Professor Campbell, who sat on the TGA’s working group, said the guidance was clear.

“This is so we can have tenecteplase available for the places that can’t use anything else,” he told the limbic.

“In metropolitan hospitals, whether it’s a stroke, a heart attack, pulmonary embolus or anything else, the choice should be alteplase until the shortage passes.”

The licensed drug for stroke is alteplase. I’m responsible for some of the evidence with tenecteplase and I think it is more effective for patients with stroke due to large vessel occlusion, but we don’t have the luxury of using it right now.”

Meanwhile in the UK, Professor Beverley Hunt, a consultant in thrombosis and haemostasis and co-founder of Thrombosis UK, told the limbic that while there was currently a “proper shortage” of tenecteplase and alteplase, there were also “impending shortages of urokinase and streptokinase”.

“We can’t get hold of all agents, and the concern must be that we have thrombolytic agents available not only for acute stroke but also for conditions such as massive pulmonary embolism, which has a 100% mortality rate if left untreated, while there are other limb threatening problems that also need to be considered for stock reserves,” she said.

“We’re not yet at the stage where shortages are affecting treatment outcomes, but the availability of urokinase is very low for the next few months, and it’s worrying that we might have shortages of everything.”

“Therefore, we’re asking clinicians to only use any new thrombolytic where there are evidence-based guidelines available.”