Metalyse 25 mg Special Precautions

The appropriate presentation of tenecteplase product should be chosen carefully and in line with the indication. Metalyse 25 mg is intended for use in acute ischaemic stroke only.
Metalyse 8,000 U (40 mg) is intended for use in acute myocardial infarction only.
Metalyse should be prescribed by physicians experienced in the use of thrombolytic treatment and with the facilities to monitor that use. This does not preclude the pre-hospital use of Metalyse. As with other thrombolytics, it is recommended that when Metalyse is administered standard resuscitation equipment and medication be available in all circumstances.
Treatment must be performed with the involvement of physicians trained and experienced in neurological care. For the indication verification remote diagnostic measures may be considered as appropriate (see Thrombolytic treatment of acute ischaemic stroke under Dosage & Administration).
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.
Bleeding: The most common complication encountered during Metalyse therapy is bleeding. The concomitant use of other active substances affecting coagulation or platelet function (e.g.,heparin) may contribute to bleeding (see also Contraindications).
As fibrin is lysed during Metalyse therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all possible bleeding sites (including those following catheter insertions, 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 Metalyse.
Should serious bleeding occur, in particular cerebral haemorrhage, concomitant heparin administration should be terminated immediately. Administration of protamine should be considered if heparin has been administered within 4 hours 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 reassessment after each administration. A target fibrinogen level of 1 g/L is desirable with cryoprecipitate infusion. Antifibrinolytic agents should also be considered.
The use of Metalyse therapy has to be carefully evaluated in order to balance the potential risks of bleeding with expected benefits under the following conditions: Low body weight <60 kg; Patients receiving oral anticoagulants treatment: The use of METALYSE may be considered when appropriate test(s) show no clinically relevant anticoagulant activity; Recent intramuscular injection or small recent traumas, such as biopsies, puncture of major vessels, cardiac massage for resuscitation.
Intracerebral haemorrhages represent the most frequent adverse event (up to approximately 19% of patients). However, this had not led to an increased overall morbidity or mortality.
The risk of intracranial haemorrhage in acute ischaemic stroke patients may be increased with the use of METALYSE.
This applies in particular in the following cases: all situations involving a high risk of haemorrhage including those listed in Contraindications; late time-to-treatment onset; patients pre-treated with acetylsalicylic acid (ASA) may have a greater risk of intracerebral haemorrhage, particularly if METALYSE treatment is delayed; compared to younger patients, patients of advanced age (over 80 years) may have a somewhat poorer outcome independent of treatment and may have an increased risk of intracerebral haemorrhage when thrombolysed. In general, the benefit-risk of thrombolysis in patients of advanced age remains positive. Thrombolysis in AIS patients should be evaluated on individual benefit-risk basis; treatment must not be initiated later than 4.5 hours after last known well because of unfavourable benefit/risk ratio mainly based on the following: positive treatment effects decrease over time; the mortality rate increases particularly in patients with prior ASA treatment; risk of symptomatic haemorrhage increases.
Hypersensitivity: Immune-mediated hypersensitivity reactions associated with the administration of METALYSE can be caused by the active substance tenecteplase, gentamicin (a trace residue from the manufacturing process) or any of the excipients (see also Contraindications).
No sustained antibody formation to the tenecteplase molecule has been observed after treatment. However, there is no experience with re-administration of METALYSE.
There is also a risk of hypersensitivity reactions mediated through a non-immunological mechanism.
Angio-oedema represents the most common hypersensitivity reaction reported with METALYSE. This risk may be enhanced in the indication acute ischaemic stroke and/or by concomitant treatment with ACE inhibitors.
Patients treated with METALYSE should be monitored for angio-oedema during and for up to 24h after administration.
If a severe hypersensitivity reaction (e.g. angio-oedema) occurs, appropriate treatment should be promptly initiated. This may include intubation.
Blood pressure monitoring: Systolic blood pressure (BP) >180 mmHg or diastolic BP >105 mmHg, or uncontrolled arterial hypertension, should be treated rapidly and aggressively in order to minimise delays to initiate thrombolysis.
BP monitoring up to 24 hours after tenecteplase treatment is necessary. Intravenous antihypertensive therapy is recommended if systolic BP >180 mmHg or diastolic BP >105 mmHg.
Special patient groups at reduced benefit-risk: The benefit/risk ratio of thrombolytic therapy is considered less favourable in patients who have had a prior stroke or in whom uncontrolled diabetes exists, although still positive in these patients.
The benefit/risk ratio of METALYSE administration should be thoroughly considered in AIS patients with the following conditions: rapidly improving symptoms; extensive infarctions (e.g. NIHSS >25); seizure at the onset of stroke; recent history of previous stroke or serious head or spinal trauma or major surgery (such as cardiac, thoracic, abdominal, or orthopaedic); elevated activated partial thromboplastin time (aPTT) at presentation; platelet count of less than 100,000/mm3; hypertension refractory to aggressive hyperacute antihypertensive treatment such that target blood pressure less than 180/105 mmHg cannot be achieved or maintained; blood glucose <2.7 mmol/L or >22.2 mmol/L.
In stroke patients the likelihood of a favourable outcome decreases with longer time from last known well to thrombolytic treatment, increasing age, increasing stroke severity and increased levels of blood glucose on admission while the likelihood of severe disability and death or symptomatic intracranial bleeding increases, independently of treatment.
Cerebral oedema: Reperfusion of the ischaemic area may induce cerebral oedema in the infarcted zone.
Effects on ability to drive and use machines: Not relevant.
Use in Children: Safety and efficacy data in children below 18 years of age are not available for METALYSE. Therefore, METALYSE is not recommended for use in children below 18 years of age.