Actilyse powder and solvent for solution for injection and for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Actilyse, powder and solvent for solution for injection and infusion

alteplase

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

1. What Actilyse is and what it is used for
2. What you need to know before Actilyse is given
3. How Actilyse is given
4. Possible side effects
5. How to store Actilyse
6. Contents of the pack and other information

1. What Actilyse is and what it is used for

The active substance in Actilyse is alteplase. It belongs to a group of medicines called thrombolytics. These medicines work by dissolving blood clots that have formed in blood vessels.

Actilyse 10 mg, 20 mg or 50 mg is used to treat diseases caused by the formation of blood clots in blood vessels, including:

• heart attacks caused by blood clots in the arteries of the heart (acute myocardial infarction)
• blood clots in the arteries of the lungs (massive acute pulmonary embolism)
• stroke caused by a blood clot in an artery of the brain (acute ischaemic stroke)

2. What you need to know before receiving Actilyse

You must not receive Actilyse:

• if you are allergic (hypersensitive) to alteplase or to any of the other components of this medicine (listed in section 6)

• if you have or have recently had a disease that increases the risk of bleeding, including:

• bleeding disorder or tendency to bleed

• serious or life-threatening bleeding anywhere in the body

• bleeding inside the brain or skull

• uncontrolled very high blood pressure

• bacterial infection or inflammation of the heart (endocarditis), or inflammation of the membranes surrounding the heart (pericarditis)

• inflammation of the pancreas (acute pancreatitis)

• stomach ulcer or intestinal ulcers

• esophageal varices (enlarged veins in the esophagus)

• blood vessel abnormalities, such as localized enlargement of an artery (aneurysm)

• certain tumors

• severe liver disease

• if you are taking medications to "thin" the blood (oral anticoagulants), unless appropriate tests show no clinically relevant activity of such medication

• if you have ever undergone surgery on the brain or spinal cord

• if you have undergone major surgery or experienced significant trauma within the past 3 months

• if you have recently had a puncture in a major blood vessel

• if you have received external cardiac massage (cardiopulmonary resuscitation) within the past 10 days

• if you have given birth within the past 10 days

Your doctor will also not administer Actilyse for the treatment of heart attacks or blood clots in the pulmonary arteries

• if you have or have ever had a stroke caused by bleeding in the brain (hemorrhagic stroke)
• if you have or have ever had a stroke of unknown cause
• if you have recently (within the past 6 months) had a stroke caused by a blood clot in a brain artery (ischemic stroke), unless it is the stroke for which you are being treated now

Additionally, your doctor will not administer Actilyse for the treatment of stroke caused by a blood clot in a brain artery (acute ischemic stroke)

• if stroke symptoms began more than 4.5 hours ago, or if it is possible that symptoms started more than 4.5 hours ago because you do not know when they began
• if your stroke presents only very mild symptoms
• if there are signs of bleeding in the brain
• if you have had a stroke within the past three months
• if symptoms improve rapidly before Actilyse is administered
• if you have a very severe stroke
• if you experienced seizures (convulsions) at the onset of the stroke
• if you have an abnormal prothrombin time (a test to assess how your blood clots). This test may be abnormal if you have received heparin (a medication used to "thin" the blood) within the past 48 hours
• if you are diabetic and have ever had a stroke
• if your platelet count (thrombocytes) in the blood is very low
• if your blood pressure is very high (above 185/110) and can only be reduced with medication
• if blood sugar (glucose) levels are very low (less than 50 mg/dl)
• if blood sugar (glucose) levels are very high (more than 400 mg/dl)
• if you are under 16 years of age. (For adolescents aged 16 years or older, see section “Your doctor will exercise special caution with Actilyse”).

Your doctor will exercise special caution with Actilyse

• if you have experienced any allergic reaction other than a sudden, potentially life-threatening allergic reaction (severe hypersensitivity) to the active substance alteplase or to any of the other components of this medicine (listed in section 6)
• if you have or have recently had any other condition that increases the risk of bleeding, such as:
• minor trauma
• biopsy (a procedure used to obtain tissue samples)
• puncture of major vessels
• intramuscular injection
• external cardiac massage
• if you have ever received Actilyse before
• if you are over 65 years of age
• if you are over 80 years of age, you may have a worse outcome regardless of treatment with Actilyse. However, overall the benefit-risk balance with Actilyse in patients over 80 years of age is positive, and age alone does not constitute a barrier to treatment with Actilyse
• if you are an adolescent aged 16 years or older, the benefit-risk ratio must be carefully evaluated individually for the treatment of acute ischemic stroke

Other medicines and Actilyse

Inform your doctor if you are using or have recently used any other medicines, including those obtained without a prescription. It is especially important that you inform your doctor if you are using or have recently used:

• medicines used to "thin" the blood, including:
• acetylsalicylic acid
• warfarin
• coumarin
• heparin
• certain medicines used to treat high blood pressure (Angiotensin Converting Enzyme inhibitors, ACE inhibitors)

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor. Your doctor will administer Actilyse only if the expected benefits outweigh the risk to your baby.

3. How Actilyse is administered

Actilyse will be prepared and administered to you by your doctor or a healthcare professional. It is not intended for self-administration.

Treatment with Actilyse should be started as soon as possible after the onset of symptoms.

There are three conditions for which Actilyse is indicated:

Heart attack (acute myocardial infarction)

The dose you will be given depends on your body weight. The maximum dose of Actilyse is 100 mg, but it will be lower if you weigh less than 65 kg.

It can be administered in two different ways:

• 90-minute dosing regimen, for patients treated within 6 hours of symptom onset. This consists of:

  • an initial intravenous bolus injection of part of the Actilyse dose
  • infusion of the remainder of the dose over the next 90 minutes.

• 3-hour dosing regimen, for patients treated between 6 and 12 hours after symptom onset. This consists of:

  • an initial intravenous bolus injection of part of the Actilyse dose
  • infusion of the remainder of the dose over the next 3 hours.

In addition to Actilyse, your doctor will give you another medicine to prevent blood clots from forming. This medicine will be given as soon as possible after the onset of chest pain.

Blood clots in the arteries of the lungs (massive acute pulmonary embolism)

The dose you will be given depends on your body weight. The maximum dose of Actilyse is 100 mg, but it will be lower if you weigh less than 65 kg.

The medicine is usually administered as follows:

• an initial intravenous bolus injection of part of the dose
• infusion of the remainder of the dose over the next 2 hours.

After treatment with Actilyse, your doctor will start (or continue) treatment with heparin (a medicine used to "thin" the blood).

Stroke caused by a blood clot in a brain artery (acute ischaemic stroke)

Actilyse should be administered within 4.5 hours of symptom onset. The earlier you receive Actilyse, the greater the benefit from treatment and the lower the likelihood of harmful adverse effects. The dose you will be given depends on your body weight. The maximum dose of this medicine is 90 mg, but it will be lower if you weigh less than 100 kg. Actilyse is administered as follows:

• an initial intravenous bolus injection of part of the dose
• infusion of the remainder of the dose over the next 60 minutes.

You must not take acetylsalicylic acid during the first 24 hours after being treated for stroke with Actilyse. Your doctor may administer a heparin injection if necessary.

If you have any further questions about the use of this product, ask your doctor or a healthcare professional.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The following adverse effects have been observed in patients treated with Actilyse:

Very common (may affect more than 1 in 10 patients)

• heart failure – treatment interruption may be required
• bleeding in the brain (cerebral haemorrhage) after treatment of a stroke caused by a blood clot in a brain artery (acute ischaemic stroke) – treatment interruption may be required
• fluid in the lungs (pulmonary oedema)
• bleeding from the damaged blood vessel (e.g. bruising)
• low blood pressure (hypotension)
• chest pain (angina pectoris)

Common (may affect up to 1 in 10 patients)

• further heart attacks
• bleeding in the brain (cerebral haemorrhage) after treatment of a heart attack (myocardial infarction) – treatment interruption may be required
• cessation of heartbeats (cardiac arrest) – treatment interruption may be required
• shock (very low blood pressure) due to heart failure – treatment interruption may be required
• bleeding in the throat
• bleeding in the stomach or intestines, including blood in vomit (haematemesis) or blood in stools (melaena or rectal bleeding), bleeding from the gums
• bleeding in body tissues causing purplish bruises (ecchymosis)
• bleeding from the urinary tract or reproductive organs, which may result in blood in the urine (haematuria)
• bleeding or bruising (haematoma) at the injection site

Uncommon (may affect up to 1 in 100 patients)

• bleeding related to the lungs, such as blood-stained sputum (haemoptysis) or bleeding in the respiratory tract – treatment interruption may be required
• nosebleeds (epistaxis)
• irregular heartbeat after blood flow to the heart has been restored
• damage to heart valves (mitral regurgitation) or to the walls separating the heart chambers (ventricular septal defect) – treatment interruption may be required
• sudden blockage of an artery in the lungs (pulmonary embolism), brain (cerebral embolism), or other body areas (systemic embolism)
• bleeding from the ear
• decrease in blood pressure

Rare (may affect up to 1 in 1,000 patients)

• bleeding into the membrane surrounding the heart (haemopericardium) – treatment interruption may be required
• internal bleeding in the back of the abdomen (retroperitoneal haemorrhage) – treatment interruption may be required
• formation of blood clots in blood vessels that may travel to other organs in the body (embolism). Symptoms depend on the organ affected
• allergic reactions, for example, hives (urticaria) and rash, difficulty breathing up to asthma (bronchospasm), fluid accumulation under the skin and mucous membranes (angioedema), low blood pressure or shock – treatment interruption may be required
• bleeding in the eye (ocular haemorrhage)
• stomach discomfort (nausea)

Very rare (may affect up to 1 in 10,000 patients)

• severe allergic reactions (e.g. life-threatening anaphylaxis) – treatment interruption may be required

• events affecting the nervous system such as:

• spasms (seizures, fits)

• difficulty speaking

• confusion or delirium (severe confusion)

• anxiety with restlessness (agitation)

• depression

• altered thoughts (psychosis)

These disorders often occur in association with a stroke caused by a blood clot or bleeding in the brain.

Frequency not known (cannot be estimated from available data)

• bleeding in internal organs, for example, bleeding in the liver (hepatic haemorrhage) – treatment interruption may be required
• formation of cholesterol crystals, which may travel to other organs in the body (cholesterol crystal embolisation). Symptoms depend on the affected organ – treatment interruption may be required
• bleeding that may require blood transfusion
• vomiting
• increase in body temperature (fever)

Patients who have experienced bleeding in the brain or other serious bleeding events may die or suffer permanent disability.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Actilyse

It is not usual for you to store Actilyse, as it will be administered to you by your doctor.

Keep this medicine out of the sight and reach of children.

Do not store above 25 °C. Store in the original packaging to protect from light.

Do not use Actilyse after the expiry date stated on the vial label and on the outer carton. The expiry date refers to the last day of the month indicated.

Reconstituted solution

The reconstituted solution has been shown to be stable for 24 hours at 2 °C–8 °C and for 8 hours at 25 °C.

From a microbiological standpoint, the product should be used immediately after reconstitution. If not used immediately, the storage duration and conditions prior to use shall be the responsibility of the user and should not exceed 24 hours at 2–8 °C.

6. Contents of the pack and other information

Composition of Actilyse

• The active substance is alteplase. Each vial contains 10 mg (equivalent to 5,800,000 IU), 20 mg (equivalent to 11,600,000 IU), or 50 mg (equivalent to 29,000,000 IU) of alteplase.

Alteplase is produced by recombinant DNA technology using a Chinese hamster ovary cell line. The other components are arginine, phosphoric acid (for pH adjustment), and polysorbate 80.

• The solvent is water for injections.

Appearance of the product and contents of the pack

Actilyse is a powder and solvent for solution for injection and for infusion. Each pack contains one vial of powder and one vial of solvent.

Actilyse is available in the following pack sizes:

• one vial of powder containing 10 mg of alteplase and one vial containing 10 ml of solvent.
• one vial of powder containing 20 mg of alteplase, one vial containing 20 ml of solvent, and a transfer cannula.
• one vial of powder containing 50 mg of alteplase, one vial containing 50 ml of solvent, and a transfer cannula.

Only some pack sizes may be commercially available.

Marketing Authorization Holder

Boehringer Ingelheim International GmbH
55216 Ingelheim am Rhein
Germany

Local representative:

Boehringer Ingelheim España, S.A.
Prat de la Riba, 50
08174 Sant Cugat del Vallès (Barcelona)
Spain

Manufacturer:

Boehringer Ingelheim Pharma GmbH & Co. KG
Birkendorfer Strasse 65
88397 Biberach/Riss
Germany

Boehringer Ingelheim France
100-104 avenue de France
75013 Paris
France

Date of the most recent revision of this summary: 09/2024

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

---

The following information is intended for healthcare professionals only:

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly documented.

The 2 mg vials of alteplase are not indicated for use in the indications of acute myocardial infarction, massive acute pulmonary embolism, or acute ischaemic stroke (due to the risk of massive underdosing). Only the 10 mg, 20 mg, and 50 mg vials are indicated for use in these indications.

Reconstitution

To obtain a final concentration of 1 mg of alteplase per ml after reconstitution, the entire volume of solvent provided should be transferred into the vial containing the Actilyse powder. For this purpose, the transfer cannula included in the 20 mg and 50 mg pack sizes should be used. For the 10 mg presentation, a syringe should be used.

To obtain a final concentration of 2 mg of alteplase per ml after reconstitution, only half of the provided solvent should be used (according to the table below). In these cases, a syringe must always be used to transfer the required amount of solvent to the vial containing Actilyse powder.

The contents of one Actilyse injection vial (10 mg, 20 mg or 50 mg) must be dissolved under aseptic conditions with water for injections, according to the table below, to obtain a final alteplase concentration of 1 mg/ml or 2 mg/ml:

Actilyse lyophilisate	10 mg	20 mg	50 mg
(a) Volume of sterile water for injectable preparations to be added to the lyophilisate	10 ml	20 ml	50 ml
Final concentration:	1 mg alteplase/ml	1 mg alteplase/ml	1 mg alteplase/ml
(b) Volume of sterile water for injectable preparations to be added to the lyophilisate	5 ml	10 ml	25 ml
Final concentration:	2 mg alteplase/ml	2 mg alteplase/ml	2 mg alteplase/ml

The reconstituted solution should then be administered intravenously. The reconstituted solution of 1 mg/ml may be further diluted with sterile sodium chloride 9 mg/ml (0.9%) injection solution to a minimum concentration of 0.2 mg/ml, as turbidity of the reconstituted solution cannot be excluded. Further dilution of the reconstituted solution of 1 mg/ml with sterile water for injection or, in general, the use of carbohydrate-containing infusion solutions, e.g. dextrose, is not recommended due to increased formation of turbidity in the reconstituted solution. Actilyse must not be mixed with other medicinal products in the same infusion vial (not even with heparin).

For storage conditions, please refer to section 5 of the package leaflet.

The reconstituted solution is for single use only. Any unused portion of the solution must be discarded.

Instructions for reconstituting Actilyse

1	Reconstitute immediately before administration.
2	Remove the protective caps from the two vials containing sterile water and Actilyse lyophilized powder, respectively, by pulling them upward with one finger.
3	Clean the rubber stopper of each vial with an alcohol wipe.
4	Remove the transfer cannula* from its packaging. Do not disinfect or sterilize the transfer cannula; it is sterile. Remove the cap.
5	Keep the vial of sterile water upright on a stable surface. From directly above, vertically pierce the center of the rubber stopper with the transfer cannula, pressing carefully but firmly, without rotating.
6	Hold the vial of sterile water and the transfer cannula firmly with one hand using both side tabs. Remove the remaining cap from the top of the transfer cannula.
7	Hold the vial of sterile water and the transfer cannula firmly with one hand using both side tabs. Hold the vial containing Actilyse lyophilized powder vertically above the transfer cannula and position the tip of the cannula directly in the center of the stopper. Push the vial with the lyophilized powder downward onto the transfer cannula from directly above, piercing the rubber stopper vertically, carefully but firmly, without rotating.
8	Invert both vials and allow the water to drain completely into the lyophilized powder.
9	Remove the empty vial of sterile water together with the transfer cannula. They may be discarded.
10	Take the vial with reconstituted Actilyse and gently rotate it to dissolve any remaining powder, but do not shake, as this may cause foaming. If bubbles occur, keep the solution still for a few minutes to allow them to disappear.
11	The reconstituted solution contains 1 mg/mL of alteplase. It should be clear and colorless to pale yellow and must not contain any particles.
12	Withdraw the required amount using only a needle and syringe. Do not use the puncture site of the transfer cannula to avoid loss.
13	Use immediately. Discard any unused solution.

(* If a transfer cannula is included in the kit. Reconstitution can also be performed using a syringe and needle.)

Dosage and administration

Acute myocardial infarction

Dosage

• 90-minute (accelerated) dosing regimen for patients with acute myocardial infarction, in whom treatment can be initiated within 6 hours of 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 followed by	15 ml	7.5 ml
50 mg as an intravenous infusion at a constant rate over the first 30 minutes, immediately followed by	50 ml	25 ml
35 mg as an intravenous infusion at a constant rate over 60 minutes, up to a total maximum dose of 100 mg	35 ml	17.5 ml

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

Volume to be administered according to alteplase concentration
1 mg/ml	2 mg/ml
15 mg as an intravenous bolus, immediately followed by	15 ml	7.5 ml
0.75 mg/kg body weight (b.w.) as intravenous infusion at a constant rate during the first 30 minutes, immediately followed by	0.75 ml/kg b.w.	0.375 ml/kg b.w.
0.5 mg/kg body weight (b.w.) as intravenous infusion at a constant rate over 60 minutes	0.5 ml/kg b.w.	0.25 ml/kg b.w.

• 3-hour dosing regimen for patients with acute myocardial infarction in whom treatment can be initiated 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 followed by	10 ml	5 ml
50 mg as an intravenous infusion at a constant rate over the first hour, immediately followed by	50 ml	25 ml
40 mg as an intravenous infusion at a constant rate over 2 hours, up to a total maximum dose of 100 mg	40 ml	20 ml

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 by	10 ml	5 ml
a continuous intravenous infusion over 3 hours, up to a maximum total dose of 1.5 mg/kg b.w.	1.5 ml/kg b.w.	0.75 ml/kg b.w.

Adjunctive treatment: Adjunctive antithrombotic treatment is recommended in accordance with current international guidelines for the treatment of patients with ST-segment elevation myocardial infarction.

Administration method

The reconstituted solution must be administered intravenously and is for immediate use.

The 2 mg alteplase vials are not indicated for use in this indication.

Massive acute pulmonary embolism

Dosing

In patients with body weight ≥ 65 kg:

A total dose of 0.1 mg/kg of alteplase should be administered over 2 hours. The following dosing regimen is the one with the most clinical experience:

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

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, immediately followed by	10 ml	5 ml
a continuous intravenous infusion over 2 hours up to a maximum total dose of 1.5 mg/kg body weight.	1.5 ml/kg body weight	0.75 ml/kg body weight

Adjunctive treatment: After treatment with Actilyse, heparin therapy should be initiated (or resumed) if aPTT values are less than twice the upper limit of normal. The infusion rate should be adjusted to maintain aPTT values within the range of 50–70 seconds (1.5 to 2.5 times the reference value).

Method of administration

The reconstituted solution must be administered intravenously and is intended for immediate use.

The 2 mg alteplase vials are not indicated for use in this indication.

Acute ischaemic stroke

Treatment should only be performed under the responsibility and supervision of a physician trained and experienced in neurovascular care; see Product Information section 4.3 Contraindications and 4.4 Special warnings and precautions for use.

Treatment with Actilyse must be initiated as soon as possible within 4.5 hours from symptom onset (see Product Information section 4.4). Beyond 4.5 hours after symptom onset in stroke, the benefit-risk balance associated with Actilyse treatment is negative, and treatment must not be administered (see Product Information section 5.1).

Dosing

The recommended total dose is 0.9 mg alteplase/kg body weight (up to a 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 minutes.

DOSE TABLE FOR ACUTE ISCHEMIC STROKE
Using the recommended standard concentration of 1 mg/ml, the volume (ml) to be administered equals the recommended dose value (mg)
Weight (kg)	Total Dose (mg)	Bolus Dose (mg)	Infusion Dose* (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

*administered at a concentration of 1 mg/ml over 60 minutes at a constant infusion rate.

Concomitant treatment: The safety and efficacy of this regimen with concomitant administration of heparin or platelet aggregation inhibitors such as acetylsalicylic acid during the first 24 hours after symptom onset have not been sufficiently investigated. Therefore, administration of intravenous heparin or platelet aggregation inhibitors such as acetylsalicylic acid should be avoided within the first 24 hours after treatment with Actilyse due to an increased risk of bleeding. 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 must be administered intravenously and is intended for immediate use.

Vials containing 2 mg of alteplase are not indicated for use in this indication.

Paediatric population

Experience with the use of Actilyse in children and adolescents is limited. Actilyse is contraindicated in the treatment of acute ischaemic stroke in children and adolescents under 16 years of age (see Summary of Product Characteristics, section 4.3). The dose in adolescents aged 16 to 17 years is the same as that for adults (see Summary of Product Characteristics, section 4.4 for recommendations on the appropriate imaging techniques to be used prior to treatment).

Adolescents aged 16 years and older should be treated according to the instructions for use described in the package leaflet for the adult population, following appropriate imaging to rule out stroke mimics and confirm arterial occlusion corresponding to the neurological deficit.