Actilyse (Alteplase)
Thrombolytic Agent — Tissue Plasminogen Activator (tPA)
Actilyse (alteplase) is a thrombolytic medicine that dissolves blood clots blocking arteries. It is used in emergency settings to treat three life-threatening conditions: acute myocardial infarction (heart attack), acute massive pulmonary embolism (blood clots in the lungs), and acute ischemic stroke (blood clots in the brain). Actilyse works by activating the body’s natural clot-dissolving system and must only be administered by trained healthcare professionals in a hospital setting.
Quick Facts
Key Takeaways
- Actilyse (alteplase) is a clot-dissolving medicine used in emergencies for heart attacks, massive pulmonary embolism, and acute ischemic stroke.
- Time is critical: for stroke, it must be given within 4.5 hours of symptom onset; for heart attack, within 12 hours. Earlier treatment leads to better outcomes.
- The most serious risk is bleeding, including intracranial hemorrhage. It must only be administered by experienced physicians in a hospital with appropriate monitoring.
- Numerous contraindications exist, including active bleeding, recent surgery, uncontrolled hypertension, and current use of oral anticoagulants.
- Alteplase is a fibrin-specific thrombolytic produced using recombinant DNA technology, offering targeted clot dissolution with a short half-life of approximately 4–5 minutes.
What Is Actilyse and What Is It Used For?
The active substance in Actilyse is alteplase, a recombinant human tissue-type plasminogen activator (rt-PA). It is produced using recombinant DNA technology in a Chinese hamster ovary (CHO) cell line. Alteplase is identical in amino acid sequence to naturally occurring human tissue plasminogen activator, a serine protease that plays a central role in the body’s fibrinolytic system. When blood clots form inappropriately within blood vessels, they can block the flow of blood to vital organs such as the heart, lungs, and brain, causing potentially fatal damage within minutes.
Actilyse works through a process called fibrin-specific thrombolysis. Unlike older, non-specific thrombolytics such as streptokinase, alteplase preferentially binds to fibrin within an existing clot. Once bound, it converts the trapped plasminogen to plasmin, which enzymatically degrades the fibrin network. This fibrin specificity means that Actilyse acts primarily at the site of the clot rather than causing widespread systemic fibrinolysis, although some systemic effects do occur. The plasma half-life of alteplase is approximately 4–5 minutes, which means that the thrombolytic effect diminishes rapidly once the infusion is stopped.
Actilyse is approved for the treatment of three major conditions caused by acute arterial thrombosis:
Acute Myocardial Infarction (Heart Attack)
A heart attack occurs when a blood clot blocks one of the coronary arteries supplying blood to the heart muscle. Without prompt treatment, the affected heart muscle begins to die. Actilyse dissolves the clot to restore blood flow, limiting the extent of cardiac damage. According to the European Society of Cardiology (ESC) guidelines, thrombolytic therapy with alteplase should be considered when primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes of first medical contact. Large randomized controlled trials, including GUSTO-I and ASSET, have demonstrated that early administration of alteplase significantly reduces mortality in acute ST-elevation myocardial infarction (STEMI).
Acute Massive Pulmonary Embolism
Pulmonary embolism occurs when a blood clot, typically originating from the deep veins of the legs, travels to and blocks the pulmonary arteries. A massive pulmonary embolism can cause sudden cardiovascular collapse and death. Actilyse is indicated for the thrombolytic treatment of massive pulmonary embolism with hemodynamic instability, as defined by persistent hypotension or shock. The ESC guidelines recommend systemic thrombolysis with alteplase as first-line treatment for high-risk pulmonary embolism with hemodynamic compromise.
Acute Ischemic Stroke
An ischemic stroke occurs when a blood clot blocks an artery in the brain, cutting off oxygen supply to brain tissue. Actilyse is the most extensively studied thrombolytic for acute ischemic stroke and remains the standard of care for intravenous thrombolysis. The landmark NINDS trial and subsequent studies including ECASS III demonstrated that alteplase given within 4.5 hours of symptom onset significantly improves functional outcomes. The American Heart Association/American Stroke Association (AHA/ASA) guidelines recommend intravenous alteplase for eligible patients presenting within 4.5 hours of last known well time. The earlier treatment is initiated, the greater the benefit and the lower the risk of complications.
Actilyse must only be administered by physicians with training and experience in thrombolytic therapy, in a hospital setting equipped with appropriate monitoring and resuscitation facilities. It is not a medication that can be self-administered or taken at home.
What Should You Know Before Receiving Actilyse?
Because Actilyse dissolves blood clots, its most significant risk is bleeding. Before administering Actilyse, your physician will perform a thorough assessment to determine whether the benefits of treatment outweigh the risks. Several absolute and relative contraindications exist, and some differ depending on the condition being treated.
Contraindications (Do Not Use)
Actilyse must not be used in any patient with the following conditions:
- Known allergy (hypersensitivity) to alteplase or any of the other ingredients (arginine, phosphoric acid, polysorbate 80)
- Active bleeding or any bleeding disorder that increases the tendency to bleed
- Severe, dangerous, or difficult-to-control bleeding in any part of the body
- History of or current intracranial hemorrhage (bleeding inside the skull)
- Uncontrolled, severely elevated blood pressure
- Bacterial endocarditis (infection of the heart valves) or pericarditis (inflammation of the membrane around the heart)
- Acute pancreatitis
- Gastrointestinal ulceration within the past 3 months
- Esophageal varices (enlarged veins in the esophagus)
- Arterial aneurysms or known vascular malformations
- Certain tumors with increased bleeding risk
- Severe liver disease, including hepatic failure, cirrhosis, or portal hypertension
- Current use of oral anticoagulants (e.g., warfarin) at therapeutic levels, unless coagulation testing confirms no clinically significant effect
- Previous brain or spinal surgery
- Major surgery or significant trauma within the past 3 months
- Recent puncture of a large blood vessel that cannot be compressed
- Cardiopulmonary resuscitation (chest compressions) within the past 10 days
- Childbirth within the past 10 days
Additional Contraindications for Stroke Treatment
When Actilyse is being considered for acute ischemic stroke, the following additional contraindications apply:
- Stroke symptom onset more than 4.5 hours ago, or unknown time of onset
- Only mild neurological deficit or rapidly improving symptoms before treatment
- Evidence of intracranial hemorrhage on brain imaging (CT or MRI)
- History of stroke within the past 3 months
- Seizure at the onset of stroke symptoms
- Blood glucose below 2.8 mmol/L or above 22.2 mmol/L
- Blood pressure exceeding 185/110 mmHg that cannot be adequately reduced with intravenous medication
- Platelet count below 100,000/µL
- Abnormal coagulation tests (INR, aPTT) due to recent heparin use
- Diabetes with any prior history of stroke
- Patient under 16 years of age (for patients 16–17, careful benefit-risk assessment required)
These contraindications are carefully evaluated by your treating physician. In an emergency, the decision to administer Actilyse always involves weighing the risk of bleeding against the immediate threat to life from the underlying condition. Do not delay calling emergency services because of concerns about contraindications — let the medical team make this assessment.
Warnings and Precautions
Your doctor will exercise particular caution when considering Actilyse if you:
- Have had any previous allergic reaction (other than anaphylaxis) to alteplase
- Have recently had minor injuries, biopsies, or intramuscular injections
- Have previously received Actilyse (re-administration may slightly increase the risk of allergic reaction)
- Are over 65 years of age (increased bleeding risk)
- Are over 80 years of age (the benefit of stroke treatment may be reduced, though age alone is not a contraindication)
Pregnancy and Breastfeeding
There is limited experience with the use of Actilyse during pregnancy. Your physician will only administer Actilyse during pregnancy if the potential benefit to you clearly outweighs the possible risk to your unborn child. Given that the conditions Actilyse treats (heart attack, stroke, massive PE) are immediately life-threatening, the decision is typically made on an individual basis in the emergency setting. It is not known whether alteplase passes into breast milk. If you are breastfeeding and have received Actilyse, discuss the timing of resuming breastfeeding with your healthcare team.
How Does Actilyse Interact with Other Drugs?
Because Actilyse dissolves blood clots, any drug that affects the coagulation system or platelet function can increase the risk of hemorrhage when used concomitantly. Actilyse is always administered in a controlled hospital setting where these interactions are carefully monitored and managed by the medical team. Inform your doctor about all medications you are currently taking or have recently taken.
| Drug / Class | Interaction | Severity | Clinical Significance |
|---|---|---|---|
| Warfarin / Coumarins | Increased bleeding risk; contraindicated if INR is elevated | Major | INR must be checked before administration; Actilyse contraindicated at therapeutic anticoagulation levels |
| Heparin (UFH / LMWH) | Additive anticoagulant effect; increases hemorrhage risk | Major | Heparin may be used after Actilyse for MI/PE but requires careful aPTT monitoring; avoid for 24 hours after stroke thrombolysis |
| Aspirin (ASA) | Antiplatelet effect increases bleeding risk | Moderate | Used as adjunctive therapy for MI; must be avoided for 24 hours after stroke thrombolysis |
| Clopidogrel / P2Y12 inhibitors | Antiplatelet effect increases bleeding risk | Moderate | Avoid antiplatelet agents for 24 hours after stroke thrombolysis; used as part of MI management |
| DOACs (apixaban, rivaroxaban, etc.) | Increased bleeding risk; stroke thrombolysis contraindicated if recent DOAC use | Major | Specific coagulation tests or reversal agents may be required before administering Actilyse |
| ACE Inhibitors | Possible increased risk of angioedema (orolingual swelling) | Moderate | Higher incidence of angioedema reported in stroke patients on ACE inhibitors receiving alteplase |
It is important to understand that Actilyse is always used in an emergency medical setting where the treating team has full awareness of concomitant medications and can manage any interactions appropriately. The benefits of thrombolytic therapy in life-threatening conditions generally outweigh the risks of drug interactions, but these must be carefully assessed on a case-by-case basis.
What Is the Correct Dosage of Actilyse?
Actilyse is prepared and administered by a physician or qualified healthcare professional. It is not intended for self-administration. The dose depends on the condition being treated and the patient’s body weight. Actilyse should always be given as early as possible after the onset of symptoms for maximum benefit.
Acute Myocardial Infarction (Heart Attack)
90-Minute (Accelerated) Regimen — Within 6 Hours of Symptom Onset
For patients weighing ≥ 65 kg:
- 15 mg as an intravenous bolus injection, immediately followed by
- 50 mg as an intravenous infusion over the first 30 minutes, then
- 35 mg as an intravenous infusion over the following 60 minutes
- Maximum total dose: 100 mg
For patients weighing < 65 kg, the dose is adjusted: 15 mg bolus, then 0.75 mg/kg over 30 minutes, then 0.5 mg/kg over 60 minutes.
3-Hour Regimen — 6 to 12 Hours After Symptom Onset
For patients weighing ≥ 65 kg:
- 10 mg as an intravenous bolus injection, immediately followed by
- 50 mg as an intravenous infusion over the first hour, then
- 40 mg as an intravenous infusion over the following 2 hours
- Maximum total dose: 100 mg
For patients weighing < 65 kg: 10 mg bolus, then up to a maximum total dose of 1.5 mg/kg body weight infused over 3 hours.
Adjunctive anticoagulant therapy (typically heparin) is recommended alongside Actilyse for heart attack treatment, in accordance with current international guidelines for STEMI management.
Acute Massive Pulmonary Embolism
Standard Regimen
For patients weighing ≥ 65 kg: total dose of 100 mg over 2 hours:
- 10 mg as an intravenous bolus over 1–2 minutes, immediately followed by
- 90 mg as an intravenous infusion over 2 hours
For patients weighing < 65 kg: 10 mg bolus, then infusion up to a maximum total dose of 1.5 mg/kg body weight over 2 hours.
After treatment with Actilyse for pulmonary embolism, 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 an aPTT between 50–70 seconds (1.5 to 2.5 times the reference value).
Acute Ischemic Stroke
Standard Regimen — Within 4.5 Hours of Symptom Onset
The recommended total dose is 0.9 mg/kg body weight (maximum 90 mg):
- 10% of the total dose as an initial intravenous bolus, immediately followed by
- 90% of the total dose as an intravenous infusion over 60 minutes
For example, for an 80 kg patient: total dose = 72 mg (7.2 mg bolus + 64.8 mg infusion over 60 minutes).
| Weight (kg) | Total Dose (mg) | Bolus (mg) | Infusion (mg) |
|---|---|---|---|
| 50 | 45.0 | 4.5 | 40.5 |
| 60 | 54.0 | 5.4 | 48.6 |
| 70 | 63.0 | 6.3 | 56.7 |
| 80 | 72.0 | 7.2 | 64.8 |
| 90 | 81.0 | 8.1 | 72.9 |
| 100+ | 90.0 | 9.0 | 81.0 |
Intravenous heparin and antiplatelet agents such as aspirin must be avoided for the first 24 hours after stroke thrombolysis due to the increased risk of intracranial hemorrhage. If heparin is required for other indications (e.g., deep vein thrombosis prevention), the dose should not exceed 10,000 IU per day administered subcutaneously.
Children and Adolescents
There is limited experience with the use of Actilyse in children and adolescents. Actilyse is contraindicated for acute ischemic stroke in children under 16 years of age. Adolescents aged 16–17 years may be treated following the adult dosing regimen after appropriate neuroimaging to exclude stroke mimics and confirm arterial occlusion corresponding to the neurological symptoms.
Overdose
Despite the fibrin specificity of alteplase, an overdose may lead to clinically significant fibrinogen depletion and a generalized bleeding tendency. If severe bleeding occurs, treatment with Actilyse must be stopped immediately. Because of the very short half-life of alteplase (approximately 4–5 minutes), the thrombolytic effect diminishes rapidly after stopping the infusion. In most cases, supportive measures such as blood product transfusion (fresh frozen plasma, cryoprecipitate, platelets) are sufficient. Antifibrinolytic agents such as tranexamic acid may be considered in life-threatening hemorrhage.
What Are the Side Effects of Actilyse?
Like all medicines, Actilyse can cause side effects, although not everybody gets them. Because Actilyse dissolves blood clots, bleeding is the most common and most clinically significant side effect. The risk of bleeding must always be weighed against the life-threatening nature of the conditions Actilyse treats. The following side effects have been reported in patients receiving Actilyse:
Very Common
- Heart failure (may require discontinuation of treatment)
- Intracranial hemorrhage (when used for stroke) — may require stopping treatment
- Pulmonary edema (fluid in the lungs)
- Bleeding at the injured blood vessel site (bruising/hematoma)
- Low blood pressure (hypotension)
- Angina pectoris (chest pain)
Common
- Reinfarction (another heart attack)
- Intracranial hemorrhage (when used for heart attack)
- Cardiac arrest (may require stopping treatment)
- Cardiogenic shock (very low blood pressure due to heart failure)
- Bleeding in the pharynx (throat)
- Gastrointestinal bleeding, including bloody vomiting or blood in stool
- Gum bleeding
- Ecchymosis (purple bruising in body tissues)
- Urogenital bleeding (blood in urine)
- Bleeding or bruising at the injection site
Uncommon
- Pulmonary hemorrhage (blood-stained sputum or airway bleeding)
- Epistaxis (nosebleed)
- Cardiac arrhythmias after blood flow is restored to the heart (reperfusion arrhythmias)
- Damage to heart valves or septal wall (may require stopping treatment)
- Systemic embolism (sudden blockage of arteries in the brain, lungs, or other organs)
- Ear hemorrhage (bleeding from the ear)
- Blood pressure drop
Rare
- Pericardial hemorrhage (bleeding around the heart)
- Retroperitoneal hemorrhage (internal bleeding behind the abdominal cavity)
- Cholesterol crystal embolism (crystals travelling to various organs)
- Allergic reactions: urticaria (hives), rash, breathing difficulties (bronchospasm), angioedema, low blood pressure or shock
- Eye hemorrhage
- Nausea
Very Rare
- Severe anaphylactic reactions (life-threatening allergic reaction)
- Neurological events: seizures, speech problems, confusion or delirium, agitation, depression, altered thinking (psychosis)
- Bleeding in internal organs (e.g., liver hemorrhage)
- Bleeding requiring blood transfusion
- Vomiting
- Fever
Death or permanent disability can result from intracranial hemorrhage or other serious bleeding events. Any signs of unusual bleeding — such as sudden severe headache, confusion, vision changes, or weakness — during or after treatment with Actilyse should be reported to the medical team immediately. Neurological assessments are performed at regular intervals during and after treatment.
Many of the reported side effects, particularly cardiac events such as arrhythmias, heart failure, and cardiogenic shock, are consequences of the underlying condition being treated (heart attack, stroke) rather than direct effects of the medication itself. The neurological events listed under “very rare” are frequently associated with ischemic stroke or cerebral hemorrhage rather than being caused by alteplase directly.
How Should Actilyse Be Stored?
Under normal circumstances, patients are not asked to store Actilyse as it is prepared and administered in a hospital setting. However, for completeness, the following storage conditions apply:
- Store below 25°C
- Keep in the original packaging to protect from light
- Do not use after the expiry date stated on the label and carton
- Keep out of the sight and reach of children
After Reconstitution
The reconstituted solution has been shown to be chemically and physically stable for 24 hours at 2–8°C and for 8 hours at 25°C. From a microbiological perspective, the solution should be used immediately after reconstitution. If not used immediately, in-use storage times and conditions are the responsibility of the user and should normally not exceed 24 hours at 2–8°C. The reconstituted solution is for single use only; any unused solution must be discarded.
What Does Actilyse Contain?
Each package of Actilyse contains a vial of powder and a vial of solvent (water for injections). The active substance is alteplase, produced using recombinant DNA technology in a Chinese hamster ovary (CHO) cell line. Actilyse is available in three strengths:
- 10 mg alteplase (equivalent to 5,800,000 IU) with 10 ml solvent
- 20 mg alteplase (equivalent to 11,600,000 IU) with 20 ml solvent and a transfer cannula
- 50 mg alteplase (equivalent to 29,000,000 IU) with 50 ml solvent and a transfer cannula
The other ingredients (excipients) are:
- Arginine
- Phosphoric acid (for pH adjustment)
- Polysorbate 80
After reconstitution with the full volume of supplied solvent, the solution has a concentration of 1 mg alteplase per ml. The reconstituted 1 mg/ml solution can be further diluted with sterile sodium chloride 9 mg/ml (0.9%) solution to a minimum concentration of 0.2 mg/ml. Further dilution with water for injections or carbohydrate-containing solutions (e.g., glucose) is not recommended due to increased turbidity. Actilyse must not be mixed with other medications in the same infusion solution, including heparin.
Actilyse is manufactured by Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany, and Boehringer Ingelheim France, Paris, France. The marketing authorization holder is Boehringer Ingelheim International GmbH, Ingelheim, Germany.
Frequently Asked Questions About Actilyse
Actilyse (alteplase) is a thrombolytic medicine used to dissolve blood clots in three emergency conditions: acute myocardial infarction (heart attack) caused by blood clots in the coronary arteries, acute massive pulmonary embolism (blood clots in the lung arteries), and acute ischemic stroke (blood clots in the brain arteries). It works by activating the body’s natural clot-dissolving system and must be administered by trained healthcare professionals in a hospital.
Actilyse begins working within minutes of intravenous administration. The plasma half-life of alteplase is approximately 4–5 minutes, meaning it is rapidly cleared from the bloodstream. For stroke treatment, it must be given within 4.5 hours of symptom onset. For heart attack, it is most effective when given within 6 hours but can be used up to 12 hours after symptom onset.
The most serious risk is hemorrhage (bleeding), especially intracranial hemorrhage (bleeding in the brain), which can be fatal or cause permanent disability. The risk of symptomatic intracranial hemorrhage with stroke thrombolysis is approximately 6–7%. Other serious risks include major gastrointestinal, retroperitoneal, or internal organ bleeding, and rare but severe allergic reactions including anaphylaxis. These risks are carefully weighed against the immediate life-threatening nature of the conditions Actilyse treats.
No. Actilyse is exclusively a hospital-administered medication. It must be given intravenously by physicians experienced in thrombolytic therapy, with continuous cardiac monitoring, blood pressure monitoring, and access to emergency resuscitation equipment. Patients require close observation during and for at least 24 hours after administration to detect and manage any bleeding complications.
Actilyse (alteplase) is fundamentally different from anticoagulants like warfarin or heparin. While anticoagulants prevent new clots from forming, Actilyse actively dissolves existing clots. It is a fibrin-specific thrombolytic, meaning it targets the fibrin within clots for more focused action. Other thrombolytics include tenecteplase (a modified version with a longer half-life allowing single-bolus dosing) and reteplase. Alteplase remains the most extensively studied thrombolytic for acute ischemic stroke.
Actilyse must be administered within 4.5 hours of stroke symptom onset. The earlier treatment is given, the better the outcomes and the lower the risk of complications. Beyond 4.5 hours, the risk-benefit ratio becomes unfavorable for intravenous thrombolysis. If the time of symptom onset is unknown (e.g., wake-up stroke), advanced brain imaging may help identify patients who could still benefit, though this requires specialist assessment.
References
- European Medicines Agency (EMA). Actilyse – Summary of Product Characteristics. Available at: www.ema.europa.eu
- Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal. 2018;39(2):119–177. doi:10.1093/eurheartj/ehx393
- Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update. Stroke. 2019;50(12):e344–e418. doi:10.1161/STR.0000000000000211
- Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism. European Heart Journal. 2020;41(4):543–603. doi:10.1093/eurheartj/ehz405
- The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue Plasminogen Activator for Acute Ischemic Stroke. New England Journal of Medicine. 1995;333(24):1581–1587. doi:10.1056/NEJM199512143332401
- Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke (ECASS III). New England Journal of Medicine. 2008;359(13):1317–1329. doi:10.1056/NEJMoa0804656
- The GUSTO Investigators. An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction. New England Journal of Medicine. 1993;329(10):673–682. doi:10.1056/NEJM199309023291001
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List (2023). Geneva: WHO; 2023.
- British National Formulary (BNF). Alteplase. Available at: bnf.nice.org.uk
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