Posology : מינונים

4.2 Posology and method of administration
Actilyse should be given as early as possible after symptom onset. The following dose guidelines apply.

Acute myocardial infarction
Posology a) 90 minutes (accelerated) dose regimen for patients with acute myocardial infarction, in whom treatment can be started within 6 hours after symptom onset.
In patients with a body weight ≥65 kg:


Volume to be administered according to alteplase concentration
1 mg/ml        2 mg/ml
15 mg as an intravenous bolus, immediately                  15 ml          7.5 ml followed by
50 mg as an intravenous constant rate infusion over         50 ml          25 ml the first 30 minutes, immediately followed by
35 mg as an intravenous constant rate infusion over         35 ml          17.5 ml 60 minutes, until the maximum total dose of 100 mg


In patients with a body weight < 65 kg the total dose should be weight adjusted according to the following table:
Volume to be administered according to alteplase concentration
1 mg/ml        2 mg/ml
15 mg as an intravenous bolus, immediately                  15 ml          7.5 ml followed by
0.75 mg/kg body weight (bw) as an intravenous               0.75 ml/kg     0.375 ml/kg constant rate infusion over the first 30 minutes,           bw             bw immediately followed by
0.5 mg/kg body weight (bw) as an intravenous                0.5 ml/kg      0.25 ml/kg constant rate infusion over 60 minutes                      bw                  bw  b) 3 h dose regimen for patients with acute myocardial infarction, in whom treatment can be started between 6 and 12 hours after symptom onset.
In patients with a body weight ≥65 kg:
Volume to be administered according to alteplase concentration
1 mg/ml        2 mg/ml
10 mg as an intravenous bolus, immediately                  10 ml          5 ml followed by
50 mg as an intravenous constant rate infusion over the     50 ml          25 ml first hour, immediately followed by
40 mg as an intravenous constant rate infusion over         40ml           20ml
2hours, until the maximum total dose of 100 mg
Actilyse                                                               Updated Prescribing Information  20 mg, 50 mg                                                                                  Feb 2023
In patients with a body weight <65 kg:
Volume to be administered according     to alteplase concentration
1 mg/ml       2 mg/ml

10 mg as an intravenous bolus, immediately followed 10 ml          5 ml by an intravenous constant rate infusion over 3 hours up to 1.5 ml/kg 0.75 ml/kg bw a maximum total dose of 1.5 mg/kg bw.                    bw


Adjunctive therapy:
Antithrombotic adjunctive therapy is recommended according to the current international guidelines for the management of patients with ST-elevation myocardial infarction;

Method of administration
The reconstituted solution should be administered intravenously and is for immediate use.
For instructions prior to reconstitution / administration, see section 6.6.

Acute Massive pulmonary embolism
Posology
In patients with a body weight ≥65 kg:
A total dose of 100 mg of alteplase should be administered in 2 hours. Most experience is available with the following dose regimen:

Volume to be administered according to alteplase concentration
1 mg/ml        2 mg/ml
10 mg as an intravenous bolus over 1 - 2 minutes,       10 ml          5 ml immediately followed by
90 mg as an intravenous constant rate infusion over     90 ml          45 ml                   2 hours until the maximum total dose of 100 mg

In patients with a body weight < 65 kg:
Volume to be administered according     to alteplase concentration
1 mg/ml   2 mg/ml
10 mg as an intravenous bolus over 1 - 2 minutes, 10 ml            5 ml immediately followed by an intravenous constant rate infusion over 2 hours up to 1.5 ml/kg 0.75 ml/kg bw a maximum total dose of 1.5 mg/kg bw                     bw


Adjunctive therapy:
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).

Method of administration
The reconstituted solution should be administered intravenously and is for immediate use.
For instructions prior to reconstitution / administration, see section 6.6.
Actilyse                                                                       Updated Prescribing Information  20 mg, 50 mg                                                                                          Feb 2023
Acute ischaemic stroke

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.

Treatment with Actilyse must be started as early as possible within 4.5 hours of the onset of symptoms (see section 4.4) . 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).

Posology
The recommended total dose is 0.9 mg alteplase/kg body weight (maximum of 90 mg) starting with 10% of the total dose as an initial intravenous bolus, immediately followed by the remainder of the total dose infused intravenously over 60 minute.
DOSING TABLE FOR ACUTE ISCHAEMIC STROKE

By using the recommended standard concentration of 1 mg/ml the volume (ml) to be administered is equal to the recommended dosing value (mg)
Weight                     Total Dose                   Bolus Dose                Infusion Dose* 
(kg)                         (mg)                         (mg)                         (mg) 
40                   36.0                    3.6                                       32.4
42                   37.8                    3.8                                       34.0
44                   39.6                    4.0                                       35.6
46                   41.4                    4.1                                       37.3
48                   43.2                    4.3                                       38.9
50                   45.0                    4.5                                       40.5 52                   46.8                    4.7                                       42.1 54                   48.6                    4.9                                       43.7 56                   50.4                    5.0                                       45.4 58                   52.2                    5.2                                       47.0 60                   54.0                    5.4                                       48.6 62                   55.8                    5.6                                       50.2 64                   57.6                    5.8                                       51.8 66                   59.4                    5.9                                       53.5 68                   61.2                    6.1                                       55.1 70                   63.0                    6.3                                       56.7 72                   64.8                    6.5                                       58.3 74                   66.6                    6.7                                       59.9 76                   68.4                    6.8                                       61.6 78                   70.2                    7.0                                       63.2 80                   72.0                    7.2                                       64.8 82                   73.8                    7.4                                       66.4 84                   75.6                    7.6                                       68.0 86                   77.4                    7.7                                       69.7 88                   79.2                    7.9                                       71.3 90                   81.0                    8.1                                       72.9 92                   82.8                    8.3                                       74.5 94                   84.6                    8.5                                       76.1 96                   86.4                    8.6                                       77.8 98                   88.2                    8.8                                       79.4 100+                   90.0                    9.0                                       81.0 *given in a concentration of 1mg/mL over 60 min as a constant rate infusion.
Actilyse                                                                   Updated Prescribing Information  20 mg, 50 mg                                                                                      Feb 2023
Adjunctive therapy:
The safety and efficacy of this regimen with concomitant administration of heparin or platelet aggregation inhibitors such as acetylsalicylic acid within the first 24 hours of onset of the symptoms have not been sufficiently investigated. Therefore, administration of intravenous heparin or platelet aggregation inhibitors such as acetylsalicylic acid should be avoided in the first 24 hours after treatment with Actilyse due to an increased haemorrhagic risk. 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.

Method of administration
The reconstituted solution should be administered intravenously and is for immediate use.
For instructions prior to reconstitution / administration, see section 6.6.
Paediatric population
There is limited experience with the use of Actilyse in children and adolescents. Actilyse is contraindicated for the treatment of acute ischaemic stroke in children and adolescents under 16 years of age (see section 4.3). The dose for adolescents 16-17 years old is the same as for adults (see section 4.4 for recommendations on prior imaging techniques to be used).