ACTILYSE®

Dosing and administration

ACTILYSE® should be given as early as possible after symptom onset.

Acute myocardial infarction

a) Ninety-minute (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:

– 15 mg as an initial intravenous bolus, immediately followed by

– 50 mg as an intravenous infusion over 30 minutes, immediately followed by

– 35 mg as an intravenous infusion over 60 minutes, until maximum total dose of 100 mg.

In patients with a body weight < 65 kg, the total dose should be weight adjusted as the following:

– 15 mg as an initial intravenous bolus, immediately followed by

– 0.75 mg/kg body weight as an intravenous infusion over 30 minutes (maximum dose 50 mg), immediately followed by

– 0.5 mg/kg body weight as an intravenous infusion over 60 minutes (maximum dose 35 mg).

b) Three-hour 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:

– 10 mg as an initial intravenous bolus, immediately followed by

– 50 mg as an intravenous infusion over 60 minutes, immediately followed by

– 40 mg as an intravenous infusion over 2 hours, until maximum total dose of 100 mg.

In patients with a body weight < 65 kg:

– Not to exceed maximum total dose of 1.5 mg/kg body weight.

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

Acute massive pulmonary embolism

A total dose of 100 mg of alteplase should be administered in 2 hours. Most experience is available with the following dose regimen:

– 10 mg as an initial intravenous bolus over 1 - 2 minutes, immediately followed by

– 90 mg as an intravenous infusion over 2 hours until maximum total dose of 100 mg.

In patients with a body weight < 65 kg, not to exceed maximum total dose of 1.5 mg/kg body weight.

Adjunctive therapy: After treatment with ACTILYSE®, heparin therapy should be initiated (or resumed) when activated partial thromboplastin time (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 folds of the reference value).

Acute ischemic stroke

Do not exceed total dose of 90 mg when treating acute ischemic stroke.

The recommended total dose is 0.9 mg/kg body weight 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 minutes.

Treatment with ACTILYSE® must be started as early as possible within 3 hours of the onset of stroke symptoms. Intracranial hemorrhage should be ruled out with appropriate imaging technique such as brain computed tomography.

 

Adjunctive therapy: The safety and efficacy of this regimen with concomitant administration of heparin or platelet aggregation inhibitors such as aspirin 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 aspirin should be avoided in the first 24 hours after treatment with ACTILYSE® due to an increased hemorrhagic 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.

Special precautions for handling

Reconstitute ACTILYSE® solution under aseptic condition. Dissolve the content of a vial of ACTILYSE® (20 mg or 50 mg) with sterilized water for injections according to the following table to obtain a final concentration of 1 mg alteplase/ml:

 

A transfer cannula is included in each of the 20-mg or 50-mg package.

Instructions for reconstituting ACTILYSE®

1	Reconstitute immediately before administration.
2	Remove the protective cap on the two vials containing the sterile water and ACTILYSE® dry substance by flipping them up with a thumb.
3	Swab the rubber top of each vial with an alcohol wipe.
4	Remove the transfer cannula† from its cover and take one cap off. The transfer cannula is sterile and does not require disinfecting or sterilizing.
5	Stand the sterile water vial upright on a stable surface. From directly above, puncture the rubber stopper vertically in the stopper center with the transfer cannula, by pressing gently but firmly, without twisting.
6	Hold the sterile water vial and the transfer cannula steady with one hand using the two side flaps. Remove the remaining cap on top of the transfer cannula.
7	Hold the sterile water vial and the transfer cannula steady with one hand using the two side flaps. Hold the vial with ACTILYSE® dry substance above the transfer cannula and position the tip of the transfer cannula right in the center of the stopper. Push down the vial with the dry substance onto the transfer cannula from directly above, puncturing the rubber stopper vertically and gently but firmly without twisting.
8	Invert the two vials and allow the water to drain completely into the dry substance.
9	Remove the empty water vial together with the transfer cannula and dispose them.
10	Take the vial with reconstituted ACTILYSE® and swirl gently to dissolve any remaining powder, but do not shake, as this will produce foam. If there are bubbles, let the solution stand undisturbed for a few minutes to allow them to disappear.
11	The solution consists of 1mg/mL ACTILYSE®. It should be clear and colorless to pale yellow and it should not contain any particles.
12	Remove the amount required using a needle and a syringe. Do not use the puncture location from the transfer cannula to avoid leakage.
13	Use immediately. Dispose of any unused solution.

 

The 1 mg/mL reconstituted solution 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 since the occurrence of turbidity of the reconstituted solution cannot be excluded. A further dilution of the 1 mg/mL reconstituted solution with sterilized water for injections or the general carbohydrate infusion solutions, e.g. dextrose, is not recommended due to increasing formation of turbidity of the reconstituted solution. ACTILYSE® should not be mixed with other medicinal products in the same infusion bottle or line (not even with heparin).