Actilyse Warnings

Treatment with Actilyse must be started as early as possible within 4.5 hours of the onset of symptoms (see Precautions). Beyond 4.5 hours after onset of stroke symptoms there is a negative benefit risk ratio associated with Actilyse administration and so it should not be administered (see Pharmacology: Pharmacodynamics under Actions).
Additional special warnings and precautions in acute ischaemic stroke: Special warnings / conditions with a decreased benefit/risk ratio: Intracerebral haemorrhage represents the major adverse reaction in the treatment of acute ischaemic stroke (up to 15% of patients without any increase of overall mortality and without any relevant increase in overall mortality and severe disability combined, i.e. modified Rankin scale [mRS] score of 5 and 6). Compared to other indications patients with acute ischaemic stroke treated with Actilyse have a markedly increased risk of intracranial haemorrhage as the bleeding occurs predominantly into the infarcted area. This applies in particular in the following cases: All situations listed in Contraindications and in general all situations involving a high risk of haemorrhage.
As time to treatment from onset of stroke symptoms increases, net clinical benefit decreases. Therefore, the administration of Actilyse should not be delayed.
Patients pre-treated with acetyl salicylic acid (ASA) may have a greater risk of intracerebral haemorrhage, particularly if Actilyse treatment is delayed.
Compared to younger patients, patients of advanced age (over 80 years) may have a somewhat poorer outcome independent of treatment. They are also more likely to have more severe strokes which are associated with a higher absolute risk of intracerebral haemorrhage when thrombolysed compared with milder strokes when thrombolysed or with non-thrombolysed patients. Although available data indicate that the net benefit of Actilyse in patients over 80 years is smaller compared with younger patients, Actilyse can be used in patients over 80 years on an individual benefit-risk basis (see Pharmacology: Pharmacodynamics under Actions). Patients of advanced age should be selected very carefully taking into account both the general health and the neurological status.
The therapeutic benefit is reduced in patients that had a prior stroke (see also Contraindications) or in those with known uncontrolled diabetes, thus the benefit/risk ratio is considered less favourable, but still positive in these patients.
In patients with very mild stroke, the risks outweigh the expected benefit (see Contraindications).
Patients with very severe stroke are at higher risk for intracerebral haemorrhage and death and should not be treated (see Contraindications).
Patients with extensive infarctions are at greater risk of poor outcome including severe haemorrhage and death. In such patients, the benefit/risk ratio should be thoroughly considered.
In stroke patients the likelihood of good outcomes decreases with longer time to treatment from onset of symptoms, increasing age, increasing stroke severity and increased levels of blood glucose on admission while the likelihood of severe disability and death or symptomatic intracranial bleedings increases, independently from treatment.
Treatment must not be initiated later than 4.5 hours after the onset of symptoms because of unfavourable benefit/risk ratio mainly based on the following: positive treatment effects decrease over time; particularly in patients with prior ASA treatment the mortality rate increases; increased risk of symptomatic haemorrhage.
Blood pressure monitoring: Blood pressure (BP) monitoring during treatment administration and up to 24 hours seems justified; an intravenous antihypertensive therapy is also recommended if systolic BP > 180 mm Hg or diastolic BP > 105 mm Hg.
Other special warnings: Reperfusion of the ischaemic area may induce cerebral oedema in the infarcted zone.
Due to an increased haemorrhagic risk, treatment with platelet aggregation inhibitors should not be initiated within the first 24 hours following thrombolysis with alteplase.