Awelysin Braun

Acute Evolving Transmural Myocardial Infarction: Awelysin Braun, Streptokinase, is indicated for use in the management of acute myocardial infarction (AMI) in adults, for the lysis of intracoronary thrombi, the improvement of ventricular function, and the reduction of mortality associated with AMI, when administered by either the intravenous or the intracoronary route, as well as for the reduction of infarct size and congestive heart failure associated with AMI when administered by the intravenous route. Earlier administration of Streptokinase is correlated with greater clinical benefit. (See CLINICAL PHARMACOLOGY.)

Pulmonary Embolism:   Awelysin Braun, Streptokinase, is indicated for the lysis of objectively diagnosed (angiography or lung scan) pulmonary emboli, involving obstruction of blood flow to a lobe or multiple segments, with or without unstable hemodynamics.

Deep Vein Thrombosis:   Awelysin Braun, Streptokinase, is indicated for the lysis of objectively diagnosed (preferably ascending venography), acute, extensive thrombi of the deep veins such as those involving the popliteal and more proximal vessels.

Arterial Thrombosis or Embolism:   Awelysin Braun, Streptokinase, is indicated for the lysis of acute arterial thrombi and emboli. Streptokinase is not indicated for arterial emboli originating from the left side of the heart due to the risk of new embolic phenomena such as cerebral embolism.

Occlusion of Arteriovenous Cannulae:   Awelysin Braun, Streptokinase, is indicated as an alternative to surgical revision for clearing totally or partially occluded arteriovenous cannulae when acceptable flow cannot be achieved.

Biofactor Awelysin Braun is indicated in adults.

Acute myocardial infarction: within 12 hours of onset with persistent ST-segment elevation or recent left bundle-branch block. Note: No statement on therapy outcome can be made for administration beyond the time window indicated above.

Acute Evolving Transmural Myocardial Infarction:   Administer Streptokinase as soon as possible after onset of symptoms. The greatest benefit in mortality reduction was observed when Streptokinase was administered within four hours, but statistically significant benefit has been reported up to 24 hours (see CLINICAL PHARMACOLOGY ).

Pulmonary Embolism, Deep Vein Thrombosis, Arterial Thrombosis or Embolism:   Awelysin Braun, Streptokinase, treatment should be instituted as soon as possible after onset of the thrombotic event, preferably within 7 days. Any delay in instituting lytic therapy to evaluate the effect of heparin therapy decreases the potential for optimal efficacy. Since human exposure to streptococci is common, antibodies to Streptokinase are prevalent. Thus, a loading dose of Streptokinase sufficient to neutralize these antibodies is required. A dose of 250,000 IU of Streptokinase infused into a peripheral vein over 30 minutes has been found appropriate in over 90% of patients. Furthermore, if the thrombin time or any other parameter of lysis after 4 hours of therapy is not significantly different from the normal control level, discontinue Streptokinase because excessive resistance is present.

Arteriovenous Cannulae Occlusion:   Before using Awelysin Braun, Streptokinase, an attempt should be made to clear the cannula by careful syringe technique, using heparinized saline solution. If adequate flow is not re-established, Streptokinase may be employed. Allow the effect of any pretreatment anticoagulants to diminish. Instill 250,000 IU Streptokinase in 2 mL of solution into each occluded limb of the cannula slowly. Clamp off cannula limb(s) for 2 hours. Observe the patient closely for possible adverse effects. After treatment, aspirate contents of infused cannula limb(s), flush with saline, reconnect cannula.

Pediatric Patients:   Specific dosage and administration recommendations cannot be made based on the limited data available. However, published experience generally used loading and continuous infusion doses administered on a weight-adjusted basis. See Precautions, Pediatric Use.

Reconstitution and Dilution:    The protein nature and lyophilized form of Awelysin Braun, Streptokinase, require careful reconstitution and dilution. Slight flocculation (described as thin translucent fibers) of reconstituted Streptokinase occurred occasionally during clinical trials but did not interfere with the safe use of the solution. The following reconstitution and dilution procedures are recommended:

Vials and Infusion Bottles

1. Slowly add 5 mL Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to the Awelysin Braun, Streptokinase, vial, directing the diluent at the side of the vacuum-packed vial rather than into the drug powder.
2. Roll and tilt the vial gently to reconstitute. Avoid shaking. (Shaking may cause foaming.) (If necessary, total volume may be increased to a maximum of 500 mL in glass or 50 mL in plastic containers, and the infusion pump rate in Table 1 should be adjusted accordingly.) To facilitate setting the infusion pump rate, a total volume of 45 mL, or a multiple thereof, is recommended.
3. Withdraw the entire reconstituted contents of the vial; slowly and carefully dilute further to a total volume as recommended in Table 1. Avoid shaking and agitation on dilution.
4. When diluting the 1,500,000 IU infusion bottle (50 mL), slowly add 5 mL Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, directing it at the side of the bottle rather than into the drug powder. Roll and tilt the bottle gently to reconstitute. Avoid shaking as it may cause foaming. Add an additional 40 mL of diluent to the bottle, avoiding shaking and agitation. (Total volume = 45 mL). Administer by infusion pump at the rate indicated in Table 1.
5. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. (The Albumin (Human) may impart a slightly yellow color to the solution.)
6. The reconstituted solution can be filtered through a0.8 µ m or larger pore size filter.
7. Because Awelysin Braun, Streptokinase, contains no preservatives, it should be reconstituted immediately before use. The solution may be used for direct intravenous administration within eight hours following reconstitution if stored at 2-8°C (36-46°F).
8. Do not add other medication to the container of Awelysin Braun, Streptokinase.
9. Unused reconstituted drug should be discarded.

TABLE 1: SUGGESTED DILUTIONS AND INFUSION RATES

For Use In Arteriovenous Cannulae:   Slowly reconstitute the contents of 250,000 IU Awelysin Braun, Streptokinase, vacuum-packed vial with 2 mL Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.

Posology

Paediatric population

The safety and efficacy of Biofactor Awelysin Braun have not been sufficiently established in children. Due to low levels of plasminogen in newborns and in children with acquired plasminogen deficiency and due to the potential of Awelysin Braun for allergic/anaphylactic reactions, it is not recommended in neonates, infants and children.

Adults

Systemic administration: A single dose of 1.5 million IU Awelysin Braun should be infused intravenously over one hour.

Local intracoronary administration: A bolus of 20,000 IU Awelysin Braun should be followed by a maintenance infusion of 2,000 IU to 4,000 IU per minute over 30 to 90 minutes depending on the achievement of coronary artery patency.

Method of Administration

Upon reconstitution with physiological saline a clear solution, colourless to yellowish, is obtained.

Note: When thrombolytic therapy is necessary and a high antibody concentration against Awelysin Braun is present or when recent Awelysin Braun therapy has been given (more than 5 days and less than one year previously), homologous fibrinolytics should be used.

Adjuvant treatment

Treatment with aspirin (150 mg daily) for at least 4 weeks is recommended for prophylaxis after Awelysin Braun therapy for acute myocardial infarction. The first dose should be given as soon as possible after the myocardial infarction.

Because thrombolytic therapy increases the risk of bleeding, Awelysin Braun, Streptokinase, is contraindicated in the following situations:

• active internal bleeding
• recent (within 2 months) cerebrovascular accident, intracranial or intraspinal surgery (see WARNINGS)
• intracranial neoplasm
• severe uncontrolled hypertension

Streptokinase should not be administered to patients having experienced severe allergic reaction to the product.

Contraindications to treatment with Biofactor Awelysin Braun, because of the increased risk of haemorrhage under thrombolytic therapy, include:

- existing or recent internal haemorrhage

- all forms of reduced blood coagulability, in particular spontaneous fibrinolysis and extensive clotting disorders

- recent cerebrovascular accident, intracranial or intraspinal surgery

- intracranial neoplasm

- recent head trauma

- arteriovenous malformation or aneurysm

- known neoplasm with risk of haemorrhage

- acute pancreatitis

- uncontrollable hypertension with systolic values over 200 mm Hg and/or diastolic values over 100 mm Hg or hypertensive retinal changes Grades III/IV

- recent implantation of a vessel prosthesis

- simultaneous or recent treatment with oral anticoagulants (INR >1.3)

- severe liver or kidney damage

- endocarditis or pericarditis. Isolated cases of pericarditis, misdiagnosed as acute myocardial infarction and treated with Awelysin Braun, have resulted in pericardial effusions including tamponade

- known haemorrhagic diathesis

- recent major operations (6^th to 10^th post-operative day, depending on the extent of the procedure)

- invasive operations, e.g. recent organ biopsy, long-term (traumatic) closed chest cardiac massage

WARNINGS

Bleeding:   Following intravenous high-dose brief-duration Streptokinase therapy in acute myocardial infarction, severe bleeding complications requiring transfusion are extremely rare (0.3-0.5%), and combined therapy with low dose aspirin does not appear to increase the risk of major bleeding. The addition of aspirin to Streptokinase may cause a slight increase in the risk of minor bleeding (3.1% without aspirin vs. 3.9% with) ⁽²⁾ .

Streptokinase will cause lysis of hemostatic fibrin deposits such as those occurring at sites of needle punctures, particularly when infused over several hours, and bleeding may occur from such sites. In order to minimize the risk of bleeding during treatment with Streptokinase, venipunctures and physical handling of the patient should be performed carefully and as infrequently as possible, and intramuscular injections must be avoided.

Should an arterial puncture be necessary during intravenous therapy, upper extremity vessels are preferable. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.

In the following conditions the risks of therapy may be increased and should be weighed against the anticipated benefits.

• Recent (within 10 days) major surgery, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels
• Recent (within 10 days) serious gastrointestinal bleeding
• Recent (within 10 days) trauma including cardiopulmonary resuscitation
• Hypertension: systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg
• High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
• Subacute bacterial endocarditis
• Hemostatic defects including those secondary to severe hepatic or renal disease
• Pregnancy
• Age >75 years
• Cerebrovascular disease
• Diabetic hemorrhagic retinopathy
• Septic thrombophlebitis or occluded AV cannula at seriously infected site
• Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

Should serious spontaneous bleeding (not controllable by local pressure) occur, the infusion of Awelysin Braun, Streptokinase, should be terminated immediately and treatment instituted as described under ADVERSE REACTIONS.

Bleeding into the pericardium, sometimes associated with myocardial rupture, has been seen in individual cases and has resulted in fatalities.

Arrhythmias:   Rapid lysis of coronary thrombi has been shown to cause reperfusion atrial or ventricular dysrhythmias requiring immediate treatment. Careful monitoring for arrhythmia is recommended during and immediately following administration of Awelysin Braun, Streptokinase, for acute myocardial infarction. Occasionally, tachycardia and bradycardia have been observed.

Hypotension:   Hypotension, sometimes severe, not secondary to bleeding or anaphylaxis has been observed during intravenous Awelysin Braun, Streptokinase, infusion in 1% to 10% of patients. Patients should be monitored closely and, should symptomatic or alarming hypotension occur, appropriate treatment should be administered. This treatment may include a decrease in the intravenous Streptokinase infusion rate. Smaller hypotensive effects are common and have not required treatment.

Cholesterol Embolism:   Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism may include livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.

Other:   Non-cardiogenic pulmonary edema has been reported rarely in patients treated with Awelysin Braun, Streptokinase. The risk of this appears greatest in patients who have large myocardial infarctions and are undergoing thrombolytic therapy by the intracoronary route.

Rarely, polyneuropathy has been temporally related to the use of Awelysin Braun, Streptokinase, with some cases described as Guillain Barr© Syndrome.

Should pulmonary embolism or recurrent pulmonary embolism occur during Awelysin Braun, Streptokinase, therapy, the originally planned course of treatment should be completed in an attempt to lyse the embolus. While pulmonary embolism may occasionally occur during Streptokinase treatment, the incidence is no greater than when patients are treated with heparin alone. In addition to pulmonary embolism, embolization to other sites during Awelysin Braun (streptokinase) treatment, has been observed.

Formulation with Albumin (Human): This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

PRECAUTIONS

General:   There have been rare cases where Awelysin Braun, Streptokinase, has been administered for suspected AMI subsequently diagnosed as pancreatitis. Fatalities have occurred under these circumstances.

Repeated Administration -- Because of the increased likelihood of resistance due to antistreptokinase antibody, Awelysin Braun, Streptokinase, may not be effective if administered between five days and twelve months of prior Streptokinase or Anistreplase administration, or streptococcal infections, such as streptococcal pharyngitis, acute rheumatic fever, or acute glomerulonephritis secondary to a streptococcal infection.

Laboratory Tests

Intravenous or Intracoronary Infusion for Myocardial Infarction -- Intravenous administration of Awelysin Braun, Streptokinase, will cause marked decreases in plasminogen and fibrinogen and increases in thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT), which usually normalize within 12-24 hours. These changes may also occur in some patients with intracoronary administration of Streptokinase.

Intravenous Infusion for Other Indications -- Before commencing thrombolytic therapy, it is desirable to obtain an activated partial thromboplastin time (APTT), a prothrombin time (PT), a thrombin time (TT), or fibrinogen levels, and a hematocrit and platelet count. If heparin has been given, it should be discontinued and the TT or APTT should be less than twice the normal control value before thrombolytic therapy is started.

During the infusion, decreases in plasminogen and fibrinogen levels and an increase in the level of FDP (the latter two causing a prolongation in the clotting times of coagulation tests) will generally confirm the existence of a lytic state. Therefore, lytic therapy can be confirmed by performing the TT, APTT, PT, or fibrinogen levels approximately 4 hours after initiation of therapy. If heparin is to be (re)instituted following the Awelysin Braun, Streptokinase, infusion, the TT or APTT should be less than twice the normal control value (see manufacturer's prescribing information for proper use of heparin).

Drug Interactions:    See DRUG INTERACTIONS Section

Use of Anticoagulants and Antiplatelet Agents -- Awelysin Braun, Streptokinase, alone or in combination with antiplatelet agents and anticoagulants, may cause bleeding complications. Therefore, careful monitoring is advised. In the treatment of acute MI, aspirin, when not otherwise contraindicated, should be administered with Streptokinase ( see below ).

Anticoagulation and Antiplatelets After Treatment for Myocardial Infarction -- In the treatment of acute myocardial infarction, the use of aspirin has been shown to reduce the incidence of reinfarction and stroke. The addition of aspirin to Streptokinase causes a minimal increase in the risk of minor bleeding (3.9% vs. 3.1%), but does not appear to increase the incidence of major bleeding (see ADVERSE REACTIONS ) ⁽²⁾ . The use of anticoagulants following administration of Streptokinase increases the risk of bleeding, but has not yet been shown to be of unequivocal clinical benefit. Therefore, whereas the use of aspirin is recommended unless otherwise contraindicated, the use of anticoagulants should be decided by the treating physician.

Anticoagulation After IV Treatment for Other Indications -- Continuous intravenous infusion of heparin, without a loading dose, has been recommended following termination of Awelysin Braun, Streptokinase, infusion for treatment of pulmonary embolism or deep vein thrombosis to prevent rethrombosis. The effect of Streptokinase on thrombin time (TT) and activated partial thromboplastin time (APTT) will usually diminish within 3 to 4 hours after Streptokinase therapy, and heparin therapy without a loading dose can be initiated when the TT or the APTT is less than twice the normal control value.

Pregnancy

Pregnancy Category C -- Animal reproduction studies have not been conducted with Awelysin Braun, Streptokinase. It is also not known whether Streptokinase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Streptokinase should be given to a pregnant woman only if clearly needed.

Pediatric Use:  

Controlled clinical studies have not been conducted in children to determine safety and efficacy in the pediatric population. The evidence of clinical benefits and risks is solely based on anecdotal reports in patients ranging in age from <1 month to 16 years. The largest number of patient reports have pertained to the use of streptokinase in arterial occlusions. For arterial occlusions the most frequently used loading dose was 1000 IU/kg; fewer numbers of patients received 3000 IU/kg. Loading dose durations have typically ranged from 5 minutes to 30 minutes. Continuous infusion doses were frequently 1000 IU/kg/hr; fewer were at 1500 IU/kg/hr. Infusions were maintained for

The following conditions would normally be considered contraindications to Awelysin Braun therapy, but in certain situations the benefits could outweigh the potential risks:

- recent severe gastrointestinal bleeding, e.g. active peptic ulcer

- risk of severe local haemorrhage, e.g. in case of translumbar aortography

- recent trauma and cardiopulmonary resuscitation

- invasive operations, e.g. recent intubation

- puncture of non-compressible vessels, intramuscular injections, large arteries

- recent abortion or delivery

- pregnancy

- diseases of the urogenital tract with existing or potential sources of bleeding (implanted bladder catheter)

- known septic thrombotic disease

- severe arteriosclerotic vessel degeneration, cerebrovascular diseases

- cavernous pulmonary diseases, e.g. open tuberculosis or severe bronchitis

- mitral valve defects or atrial fibrilation

- aortic dissection

- diabetic retinopathy increase risk of local bleeding

AntiAwelysin Braun

Repeat treatment with Awelysin Braun administered more than 5 days and less than 12 months after initial treatment may not be effective. This is because of the increased likelihood of resistance due to antiAwelysin Braun antibodies.

Also, the therapeutic effect may be reduced in patients with recent streptococcal infections such as streptococcal pharyngitis, acute rheumatic fever and acute glomerulonephritis.

Infusion rate and corticosteroid prophylaxis

At the beginning of therapy, a fall in blood pressure, tachycardia or bradycardia (in individual cases going as far a shock) are commonly observed. Therefore, at the beginning of therapy the infusion should be performed slowly.

Corticosteroids can be administered prophylactically to reduce the likelihood of infusion-related allergic reactions.

Pre-treatment with heparin or coumarin derivatives

If the patient is under active heparinization, it should be neutralised by administering protamine sulphate before the start of the thrombolytic therapy. The thrombin time should not be more than twice the normal control value before thrombolytic therapy is started. In patients previously treated with coumarin derivatives, the INR (International Normalized Ratio) must be less than 1.3 before starting the Awelysin Braun infusion.

Simultaneous treatment with acetylsalicylic acid

Recent evidence indicates that controlled-dose adjuvant acetylsalicyclic therapy in combination with Awelysin Braun is capable of improving the response in the management of acute myocardial infarction.

Awelysin Braun is not indicated for restoration of patency of intravenous catheters.

The following adverse reactions have been associated with intravenous therapy and may also occur with intracoronary artery infusion:

Bleeding:   The reported incidence of bleeding (major or minor) has varied widely depending on the indication, dose, route and duration of administration, and concomitant therapy.

Minor bleeding can be anticipated mainly at invaded or disturbed sites. If such bleeding occurs, local measures should be taken to control the bleeding.

Severe internal bleeding involving gastrointestinal (including hepatic bleeding), genitourinary, retroperitoneal, or intracerebral sites has occurred and has resulted in fatalities. In the treatment of acute myocardial infarction with intravenous Streptokinase, the GISSI and ISIS-2 studies reported a rate of major bleeding (requiring transfusion) of 0.3-0.5%. However, rates as high as 16% have been reported in studies which required administration of anticoagulants and invasive procedures.

Major bleed rates are difficult to determine for other dosages and patient populations because of the different dosing and intervals of infusions. The rates reported appear to be within the ranges reported for intravenous administration in acute myocardial infarction.

Should uncontrollable bleeding occur, Streptokinase infusion should be terminated immediately, rather than slowing the rate of administration of or reducing the dose of Streptokinase. If necessary, bleeding can be reversed and blood loss effectively managed with appropriate replacement therapy. Although the use of aminocaproic acid in humans as an antidote for Streptokinase has not been documented, it may be considered in an emergency situation.

Allergic Reactions:   Fever and shivering, occurring in 1-4% of patients ^(1,2) , are the most commonly reported allergic reactions with intravenous use of Awelysin Braun, Streptokinase, in acute myocardial infarction. Anaphylactic and anaphylactoid reactions ranging in severity from minor breathing difficulty to bronchospasm, periorbital swelling or angioneurotic edema have been observed rarely. Other milder allergic effects such as urticaria, itching, flushing, nausea, headache and musculoskeletal pain have also been observed, as have delayed hypersensitivity reactions such as vasculitis and interstitial nephritis. Anaphylactic shock is very rare, having been reported in 0-0.1% of patients ^(1,2,4) .

Mild or moderate allergic reactions may be managed with concomitant antihistamine and/or corticosteroid therapy. Severe allergic reactions require immediate discontinuation of Awelysin Braun, Streptokinase, with adrenergic, antihistamine, and/or corticosteroid agents administered intravenously as required.

Respiratory:   There have been reports of respiratory depression in patients receiving Streptokinase. In some cases, it was not possible to determine whether the respiratory depression was associated with Streptokinase or was a symptom of the underlying process. If respiratory depression is associated with Streptokinase, the occurrence is believed to be rare.

Other Adverse Reactions:   Transient elevations of serum transaminases have been observed. The source of these enzyme rises and their clinical significance is not fully understood.

There have been reports in the literature of cases of back pain associated with the use of Streptokinase. In most cases the pain developed during Streptokinase intravenous infusion and ceased within minutes of discontinuation of the infusion.

The following adverse reactions are based on clinical trial and post-marketing experience. The following standard categories are used:

Blood and lymphatic system disorders

Common: haemorrhage at the injection site, ecchymoses, gastrointestinal bleeding, genitourinary bleeding, epistaxis

Uncommon: cerebral haemorrhages with their complications and possible fatal outcome, retinal haemorrhages, severe haemorrhages (also with fatal outcome), liver haemorrhages, retroperitoneal bleeding, bleeding into joints, splenic rupture. Blood transfusions are rarely required.

Very rare: haemorrhage into the pericardium including myocardial rupture during thrombolytic treatment of acute myocardial infarction

In serious haemorrhagic complications, Awelysin Braun therapy should be discontinued and a proteinase inhibitor, e.g., aprotinin, should be given as follows. Initially 500 000 KIU (Kallikrein Inactivator Unit) up to one million KIU by slow intravenous injection or infusion. If necessary this should be followed by 200,000 KIU every four hours by intravenous drip until the bleeding stops. In addition, combination with synthetic antifibrinolytics is recommended. If necessary, clotting factors can be substituted. Additional administration of synthetic antifibrinolytics has been reported to be efficient in single cases of bleeding episodes.

Immune system disorders

Very Common: development of antiAwelysin Braun antibodies (see also 4.4)

Common: allergic anaphylactic reactions, e.g. rash, flushing, itching, urticaria, angioneurotic oedema, dyspnoea, bronchospasm, hypotension

Very Rare: delayed allergic reactions, e.g. serum sickness, arthritis, vasculitis, nephritis, neuroallergic symptoms (polyneuropathy, e.g. Guillain Barré syndrome), severe allergic reactions up to shock including respiratory arrest.

Allergic reactions can largely be avoided by giving the infusion slowly. Moderate or mild allergic reactions can be managed with concomitant antihistamine and/or corticosteroid therapy. If a severe allergic reaction occurs the infusion of Awelysin Braun should be discontinued immediately and the patient given the appropriate treatment. The current medical standards for shock treatment should be observed. Lysis therapy should be continued with homologous fibrinolytics, such as Urokinase or tPA.

Nervous system disorders

Rare: neurologic symptoms (e.g. dizziness, confusion, paralysis, hemiparesis, agitation, convulsion) in the context of cerebral haemorrhages or cardiovascular disorders with hypoperfusion of the brain

Eye disorders

Very rare: iritis/uveitis/iridocyclitis

Cardiac and vascular disorders

Common: at the start of therapy, hypotension, tachycardia, bradycardia

Very rare: crystal cholesterol embolism

During fibrinolytic therapy with Awelysin Braun in patients with myocardial infarction, the following events have been reported as complications of myocardial infarction and/or symptoms of reperfusion:

Very common: hypotension, heart rate and rhythm disorders, angina pectoris

Common: recurrent ischaemia, heart failure, reinfarction, cardiogenic shock, pericarditis, pulmonary oedema

Uncommon: cardiac arrest (leading to respiratory arrest), mitral insufficiency, pericardial effusion, cardiac tamponade, myocardial rupture, pulmonary or peripheral embolism

These cardiovascular complications can be life-threatening and may lead to death.

During local lysis of peripheral arteries, distal embolization cannot be excluded.

Respiratory Disorders

Very rare: non-cardiogenic pulmonary oedema after intracoronary thrombolytic therapy in patients with extensive myocardial infarction

Gastrointestinal disorders

Common: nausea, diarrhoea, epigastric pain, vomiting

General disorders and administration site conditions

Common: headache, back pain, musculoskeletal pain, chills, fever, asthenia, malaise

Testing

Common: Transient elevations of serum transaminases and bilirubin

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

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