Metalyse Special Precautions

Traceability: In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded.
Coronary intervention: If primary percutaneous coronary intervention (PCI) is scheduled according to the current relevant treatment guidelines, tenecteplase (see Pharmacology: Pharmacodynamics: Clinical efficacy and safety: ASSENT-4 under Actions) should not be given.
Patients who cannot undergo primary PCI within one hour as recommended by guidelines and receive tenecteplase as primary coronary recanalization treatment should be transferred without delay to a coronary intervention capable facility for angiography and timely adjunctive coronary intervention within 6-24 hours or earlier if medically indicated (see Pharmacology: Pharmacodynamics: Clinical efficacy and safety: STREAM study under Actions).
Bleeding: The most common complication encountered during tenecteplase therapy is bleeding. The concomitant use of heparin anticoagulation may contribute to bleeding. As fibrin is lysed during tenecteplase therapy, bleeding from recent puncture site may occur. Therefore, thrombolytic therapy requires careful attention to all possible bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites and needle puncture sites). The use of rigid catheters as well as intramuscular injections and non-essential handling of the patient should be avoided during treatment with tenecteplase.
Most frequently haemorrhage at the injection site, and occasionally genitourinary and gingival bleeding were observed.
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 are available as a last alternative. In the following conditions, the risk of tenecteplase therapy may be increased and should be weighed against the anticipated benefits: Systolic blood pressure >160 mmHg (see Contraindications); Cerebrovascular disease; Recent gastrointestinal or genitourinary bleeding (within the past 10 days); High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation; Any known recent (within the past 2 days) intramuscular injection; Advanced age, i.e. patients over 75 years; Low body weight <60 kg; Patients receiving oral anticoagulants.
Patients receiving oral anticoagulants: The use of Metalyse may be considered when dosing or time since the last intake of anticoagulant treatment makes residual efficacy unlikely and if appropriate test(s) of anticoagulant activity for the product(s) concerned show 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).
Arrhythmias: Coronary thrombolysis may result in arrhythmias associated with reperfusion. Reperfusion arrhythmias may lead to cardiac arrest, can be life-threatening and may require the use of conventional antiarrhythmic therapies. It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular tachyarrhythmias (pacemaker, defibrillator) is available when tenecteplase is administered.
GPIIb/IIIa antagonists: Concomitant use of GPIIb/IIIa antagonists increases bleeding risk.
Hypersensitivity/Re-administration: No sustained antibody formation to the tenecteplase molecule has been observed after treatment. However there is no systematic experience with re-administration of tenecteplase. Caution is needed when administering tenecteplase to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance, to any of the excipients, or to gentamicin (a residue from the manufacturing process). If an anaphylactoid reaction occurs, the injection should be discontinued immediately and appropriate therapy should be initiated. In any case, tenecteplase should not be re-administered before assessment of haemostatic factors like fibrinogen, plasminogen and alpha2-antiplasmin.
Effects on ability to drive and use machines: Not relevant.
Use in Children: Metalyse is not recommended for use in children (below 18 years) due to a lack of data on safety and efficacy.