Recomlyse

Recomlyse is a sterile, white, lyophilised powder for single intravenous bolus administration after reconstitution with sterile Water for Injections.
Each vial contains 1.0 x 10⁷ IU (16 mg) recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA).
The potency of Recomlyse expressed in International Units (IU) is based on a reference standard that is specific for tenecteplase. The IU for Recomlyse is not comparable with units used for other thrombolytic agents.
Excipients/Inactive Ingredients: The excipients are L-arginine, polysorbate 80, and phosphoric acid.

Pharmacotherapeutic group: Antithrombotic agents, enzymes. ATC code: B01AD11.
Pharmacology: Pharmacodynamics: Mechanism of action: Recomlyse is a tissue plasminogen activator (t-PA) produced by recombinant DNA technology, using an established mammalian cell line (Chinese Hamster Ovary cells).
Recomlyse is a recombinant plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus.
Recomlyse has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor compared to native t-PA.
After administration of Recomlyse, dose dependent consumption of α2-antiplasmin (the fluid- phase inhibitor of plasmin) with consequent increase in the level of systemic plasmin generation have been observed.
Clinical Trials: Acute myocardial infarction: In a randomized, blinded (blinded enrollment and central evaluators were blinded), parallel, active drug-controlled, multi-center clinical trial study, ST-segment elevation patients aged 18 to 70 years old and within 12 hours of onset were patients with acute myocardial infarction were used as the research subjects to evaluate the clinical safety and effectiveness of recombinant human TNK tissue plasminogen activator for injection in patients with ST-segment elevation acute myocardial infarction.
Dosage plan: This product is administered as a single bolus intravenous injection of 16 mg, and the injection is completed in 5 to 10 seconds.
Control drug: Recombinant Human Tissue Plasminogen Activator for Injection (rt-PA), the dosage is 50 mg. First, 8 mg should be injected intravenously at a constant rate, and the remaining 42 mg should be continuously pumped intravenously within 90 minutes.
Concomitant medications and usage: Heparin: intravenous and subcutaneous heparin treatment. Before thrombolysis, a heparin pulse dose of 70 IU/kg should be injected intravenously (the total amount should not exceed 5,000 IU). After thrombolysis (within 15 minutes), continuous intravenous pumping of heparin 1,000 IU/hour should be started for a total of 24 hours. Maintain APTT at 50 to 70 seconds. If APTT still cannot reach the target when the dose is increased to 1,200 IU/hour, do not increase the heparin dose. After 24 hours of thrombolysis, low molecular weight heparin was injected subcutaneously, at a dose of 1 mg/kg, and the dose was individualized, once every 12 hours for 3 to 5 days. For patients undergoing rescue PCI, intravenous heparin pumping is usually stopped after surgery, the arterial sheath is removed after 4 hours (APTT <50 seconds), and low molecular weight heparin is injected subcutaneously at a dose of 1 mg/kg, the dose is individualized, every 12 hours Once, for 3 to 5 consecutive days.
Aspirin and clopidogrel: Before thrombolysis, take a loading dose of 300 mg of enteric-coated aspirin, then 100 to 300 mg/day for 3 to 5 days, then change to 100 mg/day for long-term use. Concomitant use of clopidogrel: Take a loading dose of 300 mg orally before thrombolysis, and then 75 mg/day starting from the next day for 1 to 6 months.
Test results: A total of 251 patients entered this experimental study, with 124 patients in the experimental group (rhTNK-tPA group) and 127 patients in the control group (rt-PA). There were 93 and 89 patients in the two groups respectively who underwent coronary angiography 90 minutes after thrombosis to evaluate the re-canalization of the coronary arteries.
Efficacy: Patients with ST-segment elevation acute myocardial infarction within 12 hours of onset were intravenously injected with 16 mg rhTNK-tPA. After 90 minutes of coronary angiography evaluation, the recovery of blood flow in the infarction-related vessels is shown in Table 1. (See Table 1.)

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After thrombolysis, the 30-day mortality rate of rhTNK-tPA and rt-PA was 3.23% and 4.72% respectively, with no obvious differences (p>0.05). 30-day re-infarction was 1.61% and 2.36% respectively, recurrence rate of myocardial ischemia was 0.81% and 0.79% respectively, target revascularization was 24.19% and 16.54% respectively, there was also no difference in occurrence rate of other complications (shock, cardiac rupture, stroke and cardiac failure etc.) (p>0.05).
Safety: Safety of 16 mg rhTNK-tPA given by intravenous injection for the treatment of ST elevation acute myocardial infarction is better compared with rt-PA, severe bleeding is 0.81% and 0.79% respectively, no other severe bleeding events existed. Occurrence rate of minor bleeding event is 29.84% and 31.45% respectively. No allergic event occurred in either group. See the detailed information in Table 4.
In addition, the incidence of serious non-hemorrhagic adverse events, including cardiogenic shock, heart failure, cardiac rupture and electro-mechanical separation, ventricular fibrillation, and cardiac rupture, was 3.23% in the rhTNK-tPA group and 3.94% in the rt-PA group respectively. Non-serious non-hemorrhagic adverse events, including increasing of transaminases, myocardial enzymes, blood lipids, blood glucose and nausea, vomiting, fever, cough, etc., were mild. Most of these adverse events were judged to be unrelated to the trial drug, but related to underlying and/or concomitant diseases, and drug combination.
Acute ischemic stroke: A multi-center, prospective, centrally randomized, open-label, end-point blinded, active drug parallel control, non-inferiority phase III clinical trial compared rhTNK-tPA (0.25 mg/kg) and rt-PA (0.9 mg/kg) in the treatment of acute ischemic stroke (onset <4.5h). A total of 1,430 patients with acute ischemic stroke within 4.5 hours of onset were enrolled and randomly assigned to the experimental group and the control group at a ratio of 1:1. The experimental group received a single bolus intravenous injection of rhTNK-tPA 0.25 mg/kg (maximum The dose does not exceed 25 mg), and the control group is rt-PA 0.9 mg/kg (10% is intravenously injected, and 90% is intravenously dripped within 1 hour). The main efficacy indicator is the proportion of patients with mRS score 0-1 points on day 90±7. The secondary efficacy evaluation indicators include the proportion of patients with mRS score 0-2 points on day 90±7, mRS grade distribution, 24±2h, 7±1d or discharge from hospital. The proportion of patients whose NIHSS score was 0-1 or whose NIHSS score improved from baseline to NIHSS ≥4 points before (whichever occurs first).
A total of 1,430 patients were enrolled, of which 705 patients in the experimental group and 696 patients in the control group completed the study. There were 1,328 subjects in the PPS set, 676 in the experimental group and 652 in the control group. Demographic characteristics were similar between groups, and baseline disease characteristics were basically comparable.
The PPS analysis group, the proportion of patients with mRS scores of 0-1 points on the 90th± 7th day of the main efficacy index of the experimental group and the control group were 62.7% (421/671) and 59.2% (380/642) respectively; based on the pre-specified. After multiple imputation of missing data according to the set analysis standards, the two groups were 63.0% and 59.1% respectively. The effective rate ratio of the two groups was 1.067 (95% CI: 0.9775, 1.1636). The lower limit of the 95% CI was greater than the non-inferiority margin. The value is 0.937, rhTNK-tPA is non-inferior to rt-PA in efficacy.
In the safety analysis population, the overall mortality rates within 90 days of the experimental group and the control group were 6.5% (46/711) and 5.0% (35/706) respectively. Other important bleeding events are listed in the table as follows. (See Table 2.)

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Pharmacokinetics: After a single intravenous dose of recombinant human TNK tissue plasminogen activator for injection in healthy subjects, there is an obvious linear relationship between the peak concentration C_max, plasma concentration as well as AUC and the administered dose. The elimination half-life (t_½) is about 147 to 224 minutes and there is no dose dependence of clearance in the therapeutic dose range. The apparent volume of distribution is 3 L to 4 L, indicating that the drug is mainly distributed in the blood and is mainly metabolized by the liver.
Literatures showed that in the treatment of patients with acute myocardial infarction, after TNKase was administrated via bolus intravenous injection, the distribution in the plasma showed two stages. Its initial half-life of being cleared from plasma was 20 to 24 minutes, and its terminal half-life was 90 to 130 minutes. Of the 104 patients administrated with TNKase, 99 had mean plasma clearance ranging from 99 to 119 mL/min. The initial distribution of the drug was related to the patient's body weight and approximates the plasma volume. Hepatic metabolism was the main clearance mechanism of TNKase.
Renal and hepatic impairment: As the kidneys do not appear to be involved in the elimination of Recomlyse, it is not expected that renal dysfunction will affect the pharmacokinetics. The effect of hepatic dysfunction on pharmacokinetics of Recomlyse in humans has not been specifically investigated.
Toxicology: Preclinical safety data: Genotoxicity: The results of the Ames test and the Chinese hamster lung cell (CHL) chromosome aberration test were negative, and the results of the mouse bone marrow micronucleus test were negative.
Studies of rhTNK-tPA in animals have demonstrated its non-mutagenicity.
Studies of rhTNK-tPA in animals have not been performed to assess the carcinogenic potential.
No obvious effects on growth and development indicators and no obvious abnormalities in embryonic growth and development were seen based on the experiments on pregnant mice and rabbits.

Recomlyse is indicated in adults for the thrombolytic treatment of suspected myocardial infarction with persistent ST elevation or recent left Bundle Branch Block within 6 hours after the onset of acute myocardial infarction (AMI) symptoms.
Recomlyse is indicated for the thrombolytic treatment of the acute ischaemic stroke (AIS).
Intracranial hemorrhage must be ruled out through appropriate imaging examinations (such as head CT scan or other imaging diagnostic methods sensitive to bleeding) in advance, and treatment should be carried out as soon as possible within 4.5 hours after the onset of acute ischemic stroke symptoms.
The treatment effect is time-dependent; therefore, earlier treatment increases the probability of a favourable outcome.

Method of administration: Acute myocardial infarction: Recomlyse should be prescribed by physicians experienced in the use of thrombolytic treatment and with the facilities to monitor that use.
Treatment with Recomlyse with a single dose of 16 mg should be initiated as early as possible after onset of symptoms.
Elderly (≥75 years): Recomlyse should be administered with caution in the elderly (≥75 years) due to a higher bleeding risk.
Paediatric population: The safety and efficacy of Recomlyse in children (below 18 years) have not been established. No data are available.
Adjunctive therapy: Antithrombotic adjunctive therapy with platelet inhibitors and anticoagulants should be administered according to the current relevant treatment guidelines for the management of patients with ST-elevation myocardial infarction.
For coronary intervention see Precautions.
Method of administration: The reconstituted solution should be administered intravenously and is for immediate use.
For instructions on reconstitution of the medicinal product before administration, see Reconstitution and handling as follows.
Acute ischemic stroke: Treatment with Recomlyse should be initiated as soon as possible within 4.5 hours of onset at the recommended dose of 0.25 mg/kg body weight (maximum dose is 25 mg). The required dose should be administered as a single intravenous bolus over approximately 5-10 seconds. The volume required to administer the correct total dose can be calculated from the following scheme. (See Table 3.)

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Elderly patients (≥80 years): Recomlyse should be administered with caution in elderly patients (≥80 years) due to a higher bleeding risk.
Adjuvant therapy: The safety and effectiveness of this treatment regimen when combined with heparin or platelet aggregation inhibitors (e.g., aspirin) during the first 24 hours of symptom onset have not been adequately studied. Due to an increased risk of bleeding, intravenous heparin or the use of platelet aggregation inhibitors (e.g., aspirin) should be avoided within 24 hours of treatment with this product. If heparin is given to treat other symptoms (eg, to prevent deep vein thrombosis), the dose should not exceed 10,000 IU and should be given by subcutaneous injection.
If a patient undergoes intravascular thrombectomy after intravenous thrombolysis, the clinician should decide whether to use antiplatelet aggregation or anticoagulation therapy after assessing the benefits and risks.
Reconstitution and handling: Recomlyse should be reconstituted by adding 3 mL of Water for Injections (WFI), shake gently until completely dissolved, do not shake vigorously or foaming may occur. If foaming occurs, let the solution stand until the foam disappears. It should not be mixed with 0.9% Sodium Chloride solution or dextrose. Recomlyse is to be administered as a single intravenous bolus in about 5-10 seconds. Any unused solution should be discarded. If the reconstituted solution is not administered immediately, preserve from light, store at 2-8°C and use in 24 hours.
Recomlyse should not be mixed with other medication, neither in the same injection-vial nor the same intravenous line (not even with heparin).

This product is highly specific for fibrinogen, but overdose may still result in a reduction in fibrinogen and other coagulation factors. In the event of overdose there may be an increased risk of bleeding. In most cases, physiological regeneration is sufficient to replenish these factors after discontinuation of treatment with Recomlyse. In case of severe prolonged bleeding, substitution therapy may be considered (plasma, fresh whole blood, platelets) and synthetic antifibrinolytic agents can be used if necessary.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Recomlyse is contraindicated in the following situations because thrombolytic therapy is associated with a higher risk of bleeding: Significant bleeding disorder currently or in the past 6 months; Oral anticoagulant therapy and INR>1.3 (see Bleeding under Precautions); History of central nervous system lesions or trauma (such as intracranial tumors, arteriovenous malformations or aneurysms, intracranial and intraspinal surgeries); Known bleeding constitution; Severe uncontrolled high blood pressure; Have had serious trauma or major surgery within the past 3 months; Recent (within 2 weeks) prolonged cardiopulmonary resuscitation (>2 minutes), obstetrical delivery or non-stress vascular puncture (such as subclavian or jugular vein puncture); Severe liver disease, including hepatic failure, cirrhosis, portal hypertension (esophageal varices), and active hepatitis; Acute pancreatitis, active peptic ulcer, aneurysm, or arterial/venous malformation; Neoplasm with a tendency to bleed; Bacterial endocarditis or pericarditis; Active internal bleeding; Significant or recent severe or dangerous bleeding; Recent (within 2 weeks) prolonged cardiopulmonary resuscitation (>2 minutes), obstetrical delivery, or puncture of non-compressible blood vessel (e.g. subclavian or jugular vein puncture); Aneurysmal subarachnoid haemorrhage or suspected subarachnoid haemorrhage; Patients who are allergic to this product or any excipients.
Supplementary contraindications in the treatment of acute myocardial infarction: History of haemorrhagic stroke or unexplained stroke; History of ischemic stroke or transient ischaemic attack (TIA) within the past 6 months, except ischaemic stroke occurring within 4.5 hours; Confirmed, highly suspected, or unresolved aortic dissection.
Supplementary contraindications when treating acute ischemic stroke: It has been more than 4.5 hours since the onset of ischemic stroke symptoms and intravenous drip treatment has not been started or the time of symptom onset cannot be determined; Mild neurological deficit or rapid improvement of symptoms before starting treatment; Severe stroke assessed clinically (NIHSS>25) and/or imaging examinations; Stroke attacks are accompanied by epileptic seizures; History of stroke within the past 3 months; Acute bleeding tendency, including platelet count below 100 x 10⁹/L or other conditions; Received low molecular weight heparin treatment within 24 hours; Thrombin inhibitors or factor Xa inhibitors were used within 48 hours, and the thromboplastin time was higher than the upper limit of laboratory normal values; History of stroke combined with diabetes; Blood sugar <2.8 mmol/L or >22.22 mmol/L; Head CT or MRI shows large-scale infarction (infarct area >1/3 of the middle cerebral arteryblood supply area); Arterial puncture in a location that is not easy to compress and stop bleeding in the past week; Aortic arch dissection.

The decision to treat a patient with AIS with Recomlyse should be taken under the consultation of a physician experienced in the use of thrombolytic treatment and with the facilities to monitor its use. As with other thrombolytics, it is recommended that when Recomlyse is administered standard resuscitation equipment and medication be available in all circumstances.
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.
Coronary intervention: Transfer to a coronary intervention capable facility for adjunctive Percutaneous Coronary Intervention (PCI): Patients receiving Recomlyse as primary coronary recanalization treatment should be transferred without delay to a coronary intervention capable facility for angiography and timely coronary intervention within 6-24 hours or earlier if medically indicated.
Primary Percutaneous Coronary Intervention (PCI): For patients with acute myocardial infarction who are scheduled to undergo primary PCI as reperfusion therapy according to current relevant treatment guidelines, this product should not be used for thrombolytic therapy before primary PCI.
Bleeding: Exceeding recommended doses may increase the risk of bleeding.
In clinical studies, patients were treated with heparin, aspirin, and clopidogrel. Simultaneous use of anticoagulants and antiplatelet aggregation drugs may increase the risk of bleeding from this product. When severe bleeding occurs, anticoagulants and antiplatelet aggregation drugs should be discontinued immediately. Protamine can be used to reverse the effects of heparin. 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 clinical studies of Recomlyse, there is no experience with concomitant use of Recomlyse and warfarin or GP IIb/IIIa antagonists. The use of anticoagulants (e.g. vitamin K antagonists) and platelet aggregation inhibitors (e.g. GP IIb/IIIa antagonists) before, during or after treatment with Recomlyse is likely to increase the risk of bleeding.
The use of rigid catheters, intramuscular injections and non-essential handling of the patient should be avoided as bleeding from recent puncture sites may occur during treatment with Recomlyse. The arterial and venous puncture should be avoided after the treatment with Recomlyse. Should an arterial puncture be necessary, it is preferable to use an upper extremity vessel that is accessible to manual compression. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding. Noncompressible arterial punctures must be avoided. If venipuncture is necessary, venipunctures should be performed and monitored carefully. Puncturing of the internal jugular and subclavian veins should be avoided to reduce bleeding at noncompressible sites.
Each patient being considered for therapy with Recomlyse should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy. Especially for the following patients: Recent gastrointestinal or genitourinary bleeding within 10 days; Recent minor trauma; Any known recent intramuscular injection; Hypertension: systolic BP ≥180 mmHg and/or diastolic BP ≥110 mmHg; Haemostatic defects that are not mentioned in Contraindications, including severe renal disease; Pregnancy; Diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions; Septic thrombophlebitis or occluded AV cannula at seriously infected site; Patients currently receiving oral anticoagulants, e.g. warfarin sodium; Recent administration of GP IIb/IIIa inhibitors; Any other condition that may cause bleeding besides conditions mentioned in Contraindications.
Additional considerations when treating acute myocardial infarction: Other situations that require special attention are as follows: High likelihood of left heart thrombus, e.g. mitral stenosis with atrial fibrillation; Recent major surgery, e.g. coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of non-compressible vessels, and resuscitative cardiac compressions; Cerebrovascular disease; Advanced age (>75 years of age); Low body weight <50 kg.
Additional considerations when treating acute ischemic stroke: Intracranial hemorrhage is the main adverse event, but this does not mean that it will increase the overall disability and mortality rates. Compared with other indications, the risk of intracranial hemorrhage is significantly increased when this product is used to treat acute ischemic stroke, because bleeding mainly occurs at the infarction site.
If symptoms have occurred for more than 4.5 hours, patients should not be treated with this product (see Contraindications) due to an unfavorable benefit/risk ratio, mainly based on the following situation: over time, the expected positive therapeutic effect will be reduced. Decreased; increased mortality in patients, especially those pretreated with aspirin; increased risk of symptomatic bleeding.
Other situations that require special attention are as follows: Minor non-disabling stroke; Stroke with rapid improvement in symptoms; Neurologic impairment following a convulsive attack (related to the stroke); Extracranial cervical artery dissection; Severe trauma within the past 2 weeks (no head injury); Have a history of myocardial infarction within the past 3 months.
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.
Such arrhythmias such as sinus bradycardia, accelerated ventricular autonomic rhythm, premature ventricular depolarization, ventricular tachycardia are no different from those seen in usual clinical cases of acute myocardial infarction, and standard antimicrobial therapy can also be used. Arrhythmias are treated with medications. Concomitant antiarrhythmic treatment of bradycardia and/or ventricular excitation is recommended.
Blood pressure monitoring: Blood pressure monitoring up to 24 hours after Recomlyse treatment is necessary; intravenous antihypertensive therapy is recommended if systolic blood pressure >180 mmHg or diastolic blood pressure >105 mmHg.
Special groups at reduced benefit/risk: The benefit/risk ratio is considered less favourable in patients that had a prior stroke or in those with known uncontrolled diabetes, but still positive in these patients. Patients with extensive infarction are at high risk for poor prognosis, including the possibility of severe bleeding and death. In these patients, the benefit/risk ratio should be carefully weighed.
Patients with atrial fibrillation have certain risks when applying this product for treatment, but they can still benefit from the treatment. The benefit/risk ratio should be carefully weighed before use.
In stroke patients the likelihood of a favourable outcome decreases with longer time from onset of symptoms 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.
Due to the possible increased risk of bleeding, platelet aggregation inhibitors should not be used within 24 hours after thrombolysis with this product.
Hypersensitivity: Immune-mediated hypersensitivity reactions associated with the administration of Recomlyse can be caused by the active substance rhTNK-tPA, gentamicin (a trace residue from the manufacturing process) or any of the excipients.
Anaphylactoid reactions associated with the administration of Recomlyse can be caused byhypersensitivity to the active substance rhTNK-tPA, excipients, or stoppers containing natural rubber (latex derivatives). There is no experience with re-administration of Recomlyse. No sustained antibody formation to the rhTNK-tPA molecule has been observed after treatment, and caution should be exercised when re-administering Recomlyse.
If a severe hypersensitivity reaction occurs, appropriate treatment should be promptly initiated.
Brain edema: Reperfusion of the ischaemic area may induce cerebral oedema in the infarcted zone.
Direct PCI: For patients with acute myocardial infarction who are scheduled to undergo primary PCI as reperfusion therapy according to current relevant treatment guidelines, this product should not be used for thrombolytic therapy before primary PCI.
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 Recomlyse. Therefore, treatment of such patients is not recommended.
Use in the elderly: Compared with younger patients, patients with acute ischemic stroke over 80 years old have a higher risk of bleeding after thrombolytic treatment, and the benefit/risk ratio should be carefully weighed before use.

The experience of using this product in pregnant and lactating women is very limited, and the pros and cons should be carefully weighed.
Use in Pregnancy: There are no adequate or well controlled studies in pregnant women. Recomlyse should be given topregnant women only if the potential benefits justify the potential risk to the fetus.
Use in Lactation: It is not known if rhTNK-tPA is excreted into human milk. Caution should be exercised when Recomlyse is administered to a breast-feeding women.

Summary of the safety profile: Haemorrhage is the most common undesirable effect associated with the use of Recomlyse. The type of haemorrhage can be superficial at the injection site or internal at any site or body cavity. Death and permanent disability are reported in patients who have experienced bleeding episodes.
Tabulated list of adverse reactions: Adverse reactions related to treatment of acute myocardial infarction: The most common adverse reaction in clinical studies of this product is bleeding, including intracranial hemorrhage and other minor bleeding adverse events. The specific data are shown in Table 4. (See Table 4.)

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If a potential for massive bleeding, especially intracranial hemorrhage, is detected, thrombolytic therapy should be stopped.
Allergic Reaction: In clinical trials of this product, no allergic reactions were seen in patients after using this product. Once an allergic reaction occurs, anti-allergic treatment is required.
Other adverse events: The following adverse events were seen in patients treated with Recomlyse in clinical trials, and the impact of Recomlyse on their incidence is unclear. These adverse events include cardiogenic shock, heart failure, cardiac rupture and electromechanical dissociation, ventricular fibrillation and cardiac rupture, with an incidence rate of 3.23%; increases in aminotransferases, cardiac enzymes, blood lipids, blood sugar, and nausea, vomiting, fever, and cough etc., all to a lesser degree. Researchers judged that most of these adverse events were not related to the experimental drugs, but were related to underlying diseases and/or accompanying diseases, as well as concomitant medications.
In the ASSENT-2 study, the following non-ICH bleeding events were reported (Table 5). (See Table 5.)

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Non-intracranial major bleeding and the need for blood transfusions were lower in patients treated with TNKase.
Types of major bleeding reported in 1% or more of the patients were haematoma (1.7%) and gastrointestinal tract (1%). Types of major bleeding reported in less than 1% of the patients were urinary tract, puncture site (including cardiac catheterisation site), retroperitoneal, respiratory tract, and unspecified. Types of minor bleeding reported in 1% or more of the patients were haematoma (12.3%), urinary tract (3.7%), puncture site (including cardiac catheterisation site) (3.6%), pharyngeal (3.1%), gastrointestinal tract (1.9%), epistaxis (1.5%), and unspecified (1.3%).
Allergic Reactions: Rarely (<1%) allergic reactions (e.g., allergic symptoms, angioedema, laryngeal edema, rash, urticaria) have been reported in patients treated with TNKase. <0.1% of patients treated with TNKase have experienced allergic reactions, but causality is uncertain. When an allergic reaction occurs, conventional treatments are usually used.
Other adverse reactions: The following adverse reactions were seen in patients treated with TNKase in clinical trials. These reactions are often sequelae of the underlying disease, and the contribution of TNKase to their incidence is unknown.
These adverse reactions include cardiogenic shock, arrhythmias, atrioventricular block, pulmonary edema, heart failure, cardiac arrest, cyclic myocardial ischemia, recurrence of myocardial infarction, cardiac rupture, cardiac tamponade, pericarditis, and pericardium. fluid, mitral regurgitation, thrombosis, embolism and cardiac electromechanical dissociation. These events can be life-threatening and may result in death. Nausea and/or vomiting, hypotension, and fever have also been reported.
Adverse reactions related to treatment of acute ischemic stroke: Adverse reactions are classified according to frequency. Frequency groupings are defined according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Adverse reactions in clinical studies are as follows: Bleeding: (See Table 6.)

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When a potential tendency for massive bleeding occurs, especially intracranial hemorrhage, it needs to be treated according to clinical treatment standards. Antiplatelet aggregation drugs and anticoagulants (if any) being used should be stopped immediately, blood pressure should be controlled, and symptomatic treatment should be given promptly. Currently, the most commonly used treatment methods include hemostatic drugs (vitamin K, prothrombin complex concentrate, anti-Fibrinolytic agents, etc.), if severe bleeding occurs, alternative treatments (such as transfusion of fresh frozen plasma, whole blood, platelets, or cryoprecipitate) may be considered. If intracranial hemorrhage is evaluated by neurosurgery and surgery (decompressive craniotomy or hematoma evacuation) is required, treatment will be based on specialist advice.
Other adverse reactions: (See Table 7.)

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Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.

No formal interaction studies with Recomlyse and agents commonly administered in patients with AIS have been performed.
The use of anticoagulants (e.g., vitamin K antagonists) and anti-platelet aggregation drugs (e.g., GP IIb/IIIa antagonists) may increase the risk of bleeding prior to, during or after Recomlyse therapy.

Incompatibilities: Recomlyse is incompatible with glucose infusion solutions.
Special precautions for disposal and other handling: Any unused medicine or waste material should be disposed of in accordance with local requirements.

Shelf life: Shelf life as packaged for sale: 36 months.
Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C.
From a microbiological point of view, the product should be used immediately after reconstitution. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, protect from light.
Special precautions for storage: Store below 25°C, protect from light.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AD11 - tenecteplase ; Belongs to the class of enzymes. Used in the treatment of thrombosis.

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