Actilyse Special Precautions

Traceability: In order to improve traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded in the patient file.
The appropriate presentation of alteplase product should be chosen carefully and in accordance with the intended use. The 2 mg presentation of alteplase is not indicated for use in acute myocardial infarction, acute massive pulmonary embolism or acute ischaemic stroke (due to risk of massive under dosing). Only 10 mg, 20 mg or 50 mg presentations are indicated for use in these indications.
Thrombolytic/fibrinolytic treatment requires adequate monitoring. Actilyse should only be used under the responsibility and follow-up of physicians trained and experienced in the use of thrombolytic treatments and with the facilities to monitor that use. It is recommended that when Actilyse is administered standard resuscitation equipment and pharmacotherapy is available in all circumstances.
Hypersensitivity: Immune-mediated hypersensitivity reactions associated with the administration of Actilyse can be caused by the active substance alteplase, gentamicin (a trace residue from the manufacturing process) or any of the excipients. No sustained antibody formation to the recombinant human tissue-type plasminogen activator molecule has been observed after treatment. There is no systemic experience with re-administration of Actilyse. There is also a risk of hypersensitivity reactions mediated through a non-immunological mechanism.
Angio-oedema represents the most common hypersensitivity reaction reported with Actilyse. This risk may be enhanced in the indication acute ischaemic stroke and/or by concomitant treatment with ACE inhibitors (see Interactions). Patients treated for any authorised indication should be monitored for angio-oedema during and for up to 24h after infusion.
If a severe hypersensitivity reaction (e.g. angio-oedema) occurs, the infusion should be discontinued and appropriate treatment promptly initiated. This may include intubation.
Haemorrhages: The most common complication encountered during Actilyse therapy is bleeding. The concomitant use of heparin anticoagulation 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 cutdown and needle puncture). The use of rigid catheters, intramuscular injections and non-essential handling of the patient should be avoided during treatment with Actilyse.
If a potentially dangerous haemorrhage occurs, in particular cerebral haemorrhage, the fibrinolytic therapy must be discontinued and concomitant heparin administration should be terminated immediately. In general, however, it is not necessary to replace the coagulation factors because of the short half-life and the minimal effect on the systemic coagulation factors. Most patients who have bleeding can be managed by interruption of thrombolytic and anticoagulant therapy, volume replacement, and manual pressure applied to an incompetent vessel. Protamine should be considered if heparin has been administered within 4 hours of 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 reassessment after each administration. A target fibrinogen level of 1 g/l is desirable with cryoprecipitate infusion. Antifibrinolytic agents are available as a last alternative.
The risk of intracranial haemorrhage is increased in elderly patients, therefore in these patients the risk/benefit evaluation should be carried out carefully.
As with all thrombolytic agents, the expected therapeutic benefit should be weighed up particularly carefully against the possible risk, especially in patients with: small recent traumas, such as biopsies, puncture of major vessels, intramuscular injections, cardiac massage for resuscitation; conditions with an increased risk of haemorrhage which are not mentioned in Contraindications.
Patients receiving oral anticoagulant treatment: The use of Actilyse may be considered when dosing or time since the last intake of anticoagulant treatment makes residual efficacy unlikely confirmed by appropriate test(s) of anticoagulant activity for the product(s) concerned showing no clinically relevant activity on the coagulation system (e.g. INR≤ 1.3 for vitamin K antagonists or other relevant test(s) for other oral anticoagulants are within the respective upper limit of normal).
Additional special warnings and precautions in acute myocardial infarction and acute massive pulmonary embolism: A dose exceeding 100 mg of alteplase must not be given because it has been associated with an additional increase in intracranial bleeding. Therefore special care must be taken to ensure that the dose of alteplase infused is as described in Dosage & Administration.
The expected therapeutic benefit should be weighed up particularly carefully against the possible risk, especially in patients with systolic blood pressure > 160 mm Hg (see Contraindications) and with advanced age which may increase the risk of intracerebral haemorrhage. As the therapeutic benefit is also positive in elderly patients, the risk-benefit-evaluation should be carried out carefully.
GPIIb/IIIa antagonists: Concomitant use of GPIIb/IIIa antagonists increases the risk of bleeding.
Additional special warnings and precautions in acute myocardial infarction: Arrhythmias: Coronary thrombolysis may result in arrhythmia associated with reperfusion.
Reperfusion arrhythmias may lead to cardiac arrest, can be life threatening and may require the use of conventional antiarrhythmic therapies.
Thromboembolism: 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.
Additional special warnings and precautions in acute ischaemic stroke: Special precautions for use: Treatment must only be performed under the responsibility and follow-up of a physician trained and experienced in neurovascular care. For the verification of treatment indication remote diagnostic measures may be considered as appropriate (see Indications/Uses).
Effects on ability to drive and use machines: Not relevant.
Use in Children: As yet, there is only limited experience with the use of Actilyse in children and adolescents.
When Actilyse is considered for the treatment of acute ischaemic stroke in carefully selected adolescents ≥ 16 years of age the benefit should be weighed carefully against the risks on an individual basis and discussed with the patient and parent/guardian as appropriate. Adolescents ≥ 16 years of age should be treated according to the instruction for the adult population after imaging by appropriate techniques to rule out stroke mimics and confirming arterial occlusion corresponding to the neurological deficit (see Pharmacology: Pharmacodynamics under Actions).