Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2012 Publisher: Boehringer Ingelheim Limited Ellesfield Avenue Bracknell Berkshire RG12 8YS
Actilyse has proven to reduce 30-day-mortality in patients with acute myocardial infarction.
The diagnosis should be confirmed whenever possible by objective means such as pulmonary angiography or non-invasive procedures such as lung scanning. There is no evidence for positive effects on mortality and late morbidity related to pulmonary embolism.
Treatment must be started as early as possible within 4.5 hours after onset of stroke symptoms and after exclusion of intracranial haemorrhage by appropriate imaging techniques (e.g. cranial computerised tomography or other diagnostic imaging method sensitive for the presence of haemorrhage). The treatment effect is time-dependent; therefore earlier treatment increases the probability of a favourable outcome.
Actilyse should be given as soon as possible after symptom onset. The following dose guidelines apply.
Under aseptic conditions the content of an injection vial of Actilyse (10 mg or 20 mg or 50 mg) is dissolved with water for injections according to the following table to obtain either a final concentration of 1 mg alteplase/ml or 2 mg alteplase/ml:
Actilyse vial | 10 mg | 20 mg | 50 mg |
---|---|---|---|
Volume of water for injections to be added to dry powder: | |||
Final concentration | |||
1 mg alteplase/ml (ml) | 10 | 20 | 50 |
2 mg alteplase/ml (ml) | 5 | 10 | 25 |
The reconstituted solution should then be administered intravenously. It may be diluted further with sterile sodium chloride 9 mg/ml (0.9 %) solution for injection up to a minimal concentration of 0.2 mg/ml. A dilution of the reconstituted solution with sterilised water for injections or in general, the use of carbohydrate infusion solutions, e.g. dextrose is not recommended. Actilyse should not be mixed with other medicinal products neither in the same infusion-vial nor the same catheter (not even with heparin). For further practical instructions for preparation and handling see sections 6.2 and 6.6.
The experience in children and adolescents is limited. Actilyse is contraindicated for the treatment of acute stroke in children and adolescents (see section 4.3).
a) 90 minutes (accelerated) dose regimen for patients with myocardial infarction, in whom treatment can be started within 6 hours after symptom onset:
Concentration of alteplase | ||
1 mg/ml | 2 mg/ml | |
ml | ml | |
15 mg as an intravenous bolus | 15 | 7.5 |
50 mg as an infusion over 30 minutes | 50 | 25 |
followed by an infusion of 35 mg over 60 minutes until the maximal dose of 100 mg | 35 | 17.5 |
In patients with a body weight below 65 kg the dose should be weight adjusted according to the following table:
Concentration of alteplase | ||
1 mg/ml | 2 mg/ml | |
ml | ml | |
15 mg as an intravenous bolus | 15 | 7.5 |
ml/kg bw | ml/kg bw | |
and 0.75 mg/kg body weight (bw) over 30 minutes (maximum 50 mg) | 0.75 | 0.375 |
followed by an infusion of 0.5 mg/kg body weight (bw) over 60 minutes (maximum 35 mg) | 0.5 | 0.25 |
b) 3 h dose regimen for patients, in whom treatment can be started between 6 and 12 hours after symptom onset:
Concentration of alteplase | ||
1 mg/ml | 2 mg/ml | |
ml | ml | |
15 mg as an intravenous bolus | 10 | 5 |
50 mg as an infusion over the first hour | 50 | 25 |
ml/30 min | ml/ 30 min | |
followed by infusions of 10 mg over 30 minutes until the maximal dose of 100 mg over 3 hours | 10 | 5 |
In patients with a body weight below 65 kg the total dose should not exceed 1.5 mg/kg.
The maximum dose of alteplase is 100 mg.
Adjunctive therapy: Antithrombotic adjunctive therapy is recommended according to the current international guidelines for the management of patients with ST-elevation myocardial infarction; acetylsalicylic acid should be initiated as soon as possible after symptom onset and continued with lifelong treatment unless it is contraindicated.
A total dose of 100 mg of alteplase should be administered in 2 hours. Most experience is available with the following dose regimen:
Concentration of alteplase | ||
1 mg/ml | 2 mg/ml | |
ml | ml | |
10 mg as an intravenous bolus over 1 – 2 minutes | 10 | 5 |
followed by an intravenous infusion of 90 mg over 2 hours | 90 | 45 |
The total dose should not exceed 1.5 mg/kg in patients with a body weight below 65 kg.
After treatment with Actilyse heparin therapy should be initiated (or resumed) when aPTT values are less than twice the upper limit of normal. The infusion should be adjusted to maintain aPTT between 50 – 70 seconds (1.5 to 2.5 fold of the reference value).
Treatment must only be performed under the responsibility and follow-up of a physician trained and experienced in neurovascular care, see sections 4.3 and 4.4.
The recommended dose is 0.9 mg alteplase/kg body weight (maximum of 90 mg) infused intravenously over 60 minutes with 10% of the total dose administered as an initial intravenous bolus.
Treatment with Actilyse must be started as early as possible within 4.5 hours of the onset of symptoms. Beyond 4.5 hours after onset of stroke symptoms there is a negative benefit risk ratio associated with actilyse administration and so it should not be administered (see section 5.1).
The safety and efficacy of this regimen with concomitant administration of heparin and acetylsalicylic acid within the first 24 hours of onset of the symptoms have not been sufficiently investigated. Administration of acetylsalicylic acid or intravenous heparin should be avoided in the first 24 hours after treatment with Actilyse. If heparin is required for other indications (e.g. prevention of deep vein thrombosis) the dose should not exceed 10,000 IU per day, administered subcutaneously.
The relative fibrin specificity notwithstanding, a clinical significant reduction in fibrinogen and other blood coagulation components may occur after overdosage. In most cases, it is sufficient to await the physiological regeneration of these factors after the Actilyse therapy has been terminated. If, however, severe bleeding results, the infusion of fresh frozen plasma or fresh blood is recommended and if necessary, synthetic antifibrinolytics may be administered.
3 years.
After reconstitution, an immediate use is recommended. However, the in-use stability has been demonstrated for 24 hours at 2 °C – 8 °C and for 8 hours at 25 °C.
Store in the original package in order to protect from light.
Do not store above 25 °C.
For storage conditions of the reconstituted medicinal product, see section 6.3.
Powder for solution: 10 ml, 20 ml or 50 ml sterilised glass vials, sealed with sterile siliconised grey butyl-type stoppers with aluminium/plastic flip-off caps.
Solvent: The water for injections is filled into either 10 ml, 20 ml or 50 ml vials, depending on the size of the powder vials. The water for injections vials are sealed with rubber stoppers and aluminium/plastic flip-off caps.
Transfer cannulas (included with pack sizes of 20 mg and 50 mg only)
10 mg:
20 mg:
50 mg:
Not all pack sizes may be marketed.
For reconstitution to a final concentration of 1 mg altpelase per ml the full volume of solvent provided should be transfered to the vial containing the Actilyse powder. To this purpose a transfer cannula is included with the 20 mg and 50 mg pack sizes, which is to be used. For the 10 mg pack sizes a syringe should be used.
For reconstitution to a final concentration of 2 mg alteplase per ml only half of the solvent provided should be used. In these cases always a syringe should be used to transfer the required amount of solvent to the vial containing the Actilyse powder.
A table giving the volumes of solvent required for reconstitution to the final concentrations for each pack size is provided in section 4.2.
When reconstituting the product from the respective amount of powder and solvent, the mixture should only be agitated gently until complete dissolution. Any vigorous agitation should be avoided to prevent foam formation.
The reconstituted preparation is a clear and colourless to pale yellow solution. Prior to administration it should be inspected visually for particles and colour.
The reconstituted solution is for single use only. Any unused solution should be discarded.
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