Actilyse Special Precautions

Actilyse should be used by physicians experienced in the use of thrombolytic treatment and with facilities to monitor the use. As with other thrombolytics, it is recommended that when Actilyse is administered, standard resuscitation equipment and medication be available in all circumstances.
General: Bleeding: The most common complication encountered during Actilyse therapy is bleeding. The concomitant use of heparin anticoagulant may contribute to bleeding. As fibrin is lysed during Actilyse therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all possible bleeding sites (including those following catheter insertion, arterial and venous puncture cut down and needle puncture). The use of rigid catheters, IM injections and non-essential handling of the patient should be avoided during treatment with Actilyse.
Should serious bleeding occur, in particular cerebral haemorrhage, the fibrinolytic therapy must be discontinued and concomitant heparin administration should be terminated immediately. Administration of protamine should be considered if heparin has been administered within 4 hrs before the onset of bleeding. In the few patients who fail to respond to these conservative measures, judicious use of transfusion products may be indicated. Transfusion of cryoprecipitate, fresh frozen plasma and platelets should be considered with clinical and laboratory re-assessment after each administration. A target fibrinogen level of 1 g/L is desirable with cryoprecipitate infusion. Antifibrinolytic agents should also be considered.
A dose >100 mg of Actilyse should not be given in acute myocardial infarction as well as pulmonary embolism and 90 mg in acute ischaemic stroke because it has been associated with an increase in intracranial bleeding.
As with all thrombolytics, the use of ACTILYSE therapy has to be carefully evaluated in order to balance the potential risks of bleeding with expected benefits under the following conditions: recent intramuscular injection or small recent traumas, such as biopsies, puncture of major vessels, cardiac massage for resuscitation; conditions with an increased risk of haemorrhage, which are not mentioned under contraindications.
Patients receiving oral anticoagulants treatment: The use of ACTILYSE may be considered when appropriate test(s) of anticoagulant activity for the product(s) concerned show no clinically relevant activity. For the treatment of acute myocardial infarction and acute pulmonary embolism the following special warnings and precautions apply in addition: Systolic blood pressure > 160 mmHg; advanced age, which may increase the risk of intracerebral haemorrhage. As the therapeutic benefit is also increased in elderly patients, the risk-benefit-evaluation should be carried out carefully. For the treatment of acute myocardial infarction the following special warnings and precautions apply in addition: Arrhythmias: Coronary thrombolysis may result in arrhythmia associated with reperfusion. Referfusion arrhythmias may lead to cardiac arrest, can be life threatening and may require the use of the conventional antiarrhytmic therapies. Glyco-ProteinIIb/IIIa antagonists: The concomitant use of GPIIb/IIIa antagonists increases the risk of bleeding. Thrombo-embolism: The use of thrombolytics can increase the risk of thrombo-embolic events in patients with left heart thrombus, e.g., mitral stenosis or atrial fibrillation. For the treatment of acute ischaemic stroke the following special warnings and precautions apply in addition: Treatment must be performed under the responsibility of a physician trained and experienced in neurological care. For the verification of treatment indication remote diagnostic measures may be considered as appropriate (see Thrombolytic treatment of acute ischaemic stroke under Indications). 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 section Contraindications and in general all situations involving a high risk of haemorrhage; small asymptomatic aneurysms of the cerebral vessels; late time-to-treatment onset; patients pre-treated with acetyl salicylic acid (ASA) may have a greater risk of intracerebral haemorrhage, particularly if ACTILYSE treatment is delayed. Not more than 0.9 mg alteplase/kg bodyweight (max. of 90 mg) should be administered in view of the increased risk of cerebral haemorrhage; patients over 80 years of age may have an increased risk of intracerebral haemorrhage and a reduced net benefit from treatment compared to younger patients. Therefore, the use of ACTILYSE should be weighed carefully against anticipated risks on an individual patient basis. Treatment should 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 (BP) monitoring during treatment administration and up to 24 hours is necessary; i.v. antihypertensive therapy is recommended if systolic BP > 180 mmHg or diastolic BP > 105 mmHg. The therapeutic benefit is reduced in patients who have had a prior stroke or in whom uncontrolled diabetes exists. The benefit/risk ratio is considered less favourable, although still positive in these patients. In patients with very mild stroke, the risks outweigh the expected benefit and they should not be treated with ACTILYSE. Patients with very severe stroke are at higher risk of intracerebral haemorrhage and death and should not be treated with ACTILYSE. 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 a favourable outcome decreases with increasing age, increasing stroke severity and increased levels of blood glucose on admission while the likelihood of severe disability and death or relevant intracranial bleeding increases, independently of treatment. Patients over 80, patients with severe stroke (as assessed clinically and/or by appropriate imaging techniques) and patients with blood glucose levels < 50 mg/dL or > 400 mg/dL at baseline should not be treated with ACTILYSE. 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. As yet, there is only limited experience with the use of ACTILYSE in children.
Use in pregnancy & lactation: Pregnancy: There is limited amount of data from the use of ACTILYSE in pregnant women. Nonclinical studies performed with alteplase in doses higher than human doses exhibited fetal immaturity and/or embryotoxicity, secondary to the known pharmacological activity of the drug. Alteplase is not considered to be teratogenic (see Pharmacology: Toxicology under Actions). In cases of an acute life-threatening disease the benefit has to be evaluated against the potential risk.
Lactation: It is not known if alteplase is excreted into human milk.
Fertility: Clinical data on fertility are not available for ACTILYSE. Nonclinical studies performed with alteplase showed no adverse effect on fertility (see Pharmacology: Toxicology under Actions).
Use in children: ACTILYSE is not indicated for the therapy of acute stroke in children and adolescents under 18 years.
Use in the elderly: For use in patients above 80 years of age, see previously mentioned.