Metalyse (Tenecteplase)
Thrombolytic agent for the treatment of acute myocardial infarction (heart attack)
Metalyse contains tenecteplase, a recombinant fibrin-specific plasminogen activator used to dissolve blood clots in the coronary arteries during an acute heart attack. It is given as a single weight-based intravenous injection in hospital emergency settings, ideally within 6 hours of symptom onset, and has been proven to save lives.
Quick Facts
Key Takeaways
- Metalyse (tenecteplase) is a clot-dissolving medicine used in hospital to treat acute heart attacks within 6 hours of symptom onset.
- It is given as a single weight-based intravenous injection, making it faster and simpler to administer than older thrombolytics.
- Bleeding is the most common side effect; intracranial hemorrhage is rare but potentially life-threatening.
- It must never be given to patients with active bleeding, recent hemorrhagic stroke, or those on oral anticoagulants.
- Metalyse has been proven in large clinical trials (ASSENT-2) to save lives and is recommended in European and international guidelines.
What Is Metalyse and What Is It Used For?
Metalyse belongs to a group of medicines called thrombolytic agents (also known as fibrinolytics or clot busters). These medicines work by activating the body's natural clot-dissolving system. The active ingredient, tenecteplase, is a recombinant (genetically engineered) fibrin-specific plasminogen activator. This means it selectively targets the fibrin protein within blood clots and converts trapped plasminogen into plasmin, the enzyme that breaks down the clot.
When a coronary artery becomes blocked by a blood clot during a heart attack, the heart muscle downstream of the blockage is starved of oxygen and begins to die. Every minute of delay in restoring blood flow increases the extent of permanent heart damage. Metalyse is designed to be administered as rapidly as possible to dissolve the obstructing clot and restore coronary blood flow, a process called reperfusion.
Metalyse is specifically indicated for the treatment of ST-elevation myocardial infarction (STEMI) within 6 hours of symptom onset. STEMI is the most severe type of heart attack, characterised by a complete blockage of a coronary artery. The drug is administered as a single intravenous bolus injection, which is a significant practical advantage over older thrombolytics that required prolonged infusions over 60–90 minutes.
Large-scale clinical trials, including the landmark ASSENT-2 trial involving over 16,000 patients, demonstrated that tenecteplase is equivalent to alteplase (the previous standard thrombolytic) in reducing mortality at 30 days, while offering a simpler, faster method of administration. The European Society of Cardiology (ESC) recommends fibrinolytic therapy, including tenecteplase, when primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes of first medical contact.
It is important to note that Metalyse is a hospital-only medicine. It must be administered by a physician with experience in thrombolytic therapy, typically in an emergency department, coronary care unit, or pre-hospital setting (such as an ambulance staffed with trained emergency physicians). Anticoagulant therapy (such as heparin) and antiplatelet agents (such as aspirin and clopidogrel) are typically given alongside Metalyse as part of a comprehensive acute coronary syndrome protocol.
What Should You Know Before Receiving Metalyse?
Because thrombolytic therapy carries a significant risk of bleeding, your doctor must carefully weigh the potential benefits of dissolving the coronary clot against the risk of causing hemorrhage elsewhere in the body. A thorough medical history and assessment of contraindications is mandatory before Metalyse is administered.
Contraindications
Your doctor will not give Metalyse if you have any of the following conditions:
- A history of severe allergic reaction (anaphylaxis) to tenecteplase, any of the excipients, or gentamicin (a trace residue from the manufacturing process)
- A current or recent bleeding disorder or condition associated with increased bleeding risk
- Hemorrhagic stroke or stroke of unknown origin at any time in the past
- Ischemic stroke (stroke caused by a blood clot) within the previous 6 months
- Severely uncontrolled high blood pressure
- Recent significant head trauma or cranial surgery
- Severe liver disease, including liver failure, cirrhosis, portal hypertension, or esophageal varices
- Active peptic ulcer disease (stomach or duodenal ulcers)
- Vascular malformations such as arteriovenous malformations or aneurysms
- Certain tumours with increased bleeding risk
- Pericarditis (inflammation of the sac around the heart) or bacterial endocarditis (infection of the heart valves)
- Dementia
- Current use of oral anticoagulants (e.g., warfarin, acenocoumarol)
- Acute pancreatitis
- Recent major surgery of the brain or spinal cord
Warnings and Precautions
Your doctor will exercise particular caution and closely monitor you if any of the following apply:
- Previous mild or moderate allergic reaction to tenecteplase, excipients, or gentamicin
- High blood pressure (even if currently controlled)
- Recent bleeding from the gastrointestinal tract, urinary tract, or reproductive organs within the past 10 days
- Heart valve disease (e.g., mitral stenosis) combined with atrial fibrillation
- Recent intramuscular injection
- Age 75 years or older (increased bleeding risk)
- Body weight less than 50 kg
- Cardiopulmonary resuscitation (CPR) lasting more than 2 minutes prior to administration
- Previous administration of Metalyse (re-administration)
If you experience any signs of serious bleeding during or after treatment, such as sudden severe headache, confusion, vision changes, blood in urine or stool, or excessive bleeding from any site, medical staff must be notified immediately. Resuscitation equipment must be immediately available during and after administration.
Pregnancy and Breastfeeding
There is limited clinical experience with tenecteplase during pregnancy. The potential benefits of treating a life-threatening heart attack must be weighed against the possible risks to the developing foetus. If you are pregnant, suspect you may be pregnant, or are breastfeeding, your doctor will consider these factors before deciding to administer Metalyse. In most cases, a heart attack is a life-threatening emergency where the benefit of treatment outweighs the risk.
Children and Adolescents
Metalyse is not recommended for use in children and adolescents under 18 years of age, as there is insufficient clinical data on safety and efficacy in this age group. Acute myocardial infarction is exceedingly rare in paediatric populations.
This medicine contains 3.2 mg or 4.0 mg polysorbate 20 per 40 mg or 50 mg vial, respectively. Polysorbates may cause allergic reactions in sensitive individuals. Inform your doctor if you have any known allergies to polysorbate-containing products.
How Does Metalyse Interact with Other Drugs?
The primary concern with drug interactions involving Metalyse is the additive risk of bleeding. Because tenecteplase dissolves blood clots by activating the fibrinolytic system, any other drug that impairs blood clotting will increase the likelihood and severity of hemorrhagic complications. Despite this risk, certain anticoagulant and antiplatelet agents are co-administered as part of evidence-based acute coronary syndrome protocols.
In clinical practice, patients receiving Metalyse for acute STEMI routinely receive aspirin (acetylsalicylic acid) and anticoagulation with unfractionated heparin (UFH) or enoxaparin (a low-molecular-weight heparin). This combination increases bleeding risk but is well-established to improve clinical outcomes. The ESC guidelines provide specific dosing recommendations for these adjunctive therapies.
Major Interactions
| Drug / Class | Interaction | Clinical Significance |
|---|---|---|
| Warfarin / Coumarins | Additive anticoagulant effect. Contraindicated if currently on treatment. | Metalyse must not be given to patients actively taking oral anticoagulants. |
| Heparin (UFH / LMWH) | Synergistic anticoagulant effect. Routinely co-administered per protocol. | Required adjunctive therapy. Dose must be carefully titrated; monitor aPTT closely. |
| GP IIb/IIIa Inhibitors | Major additive bleeding risk from combined platelet inhibition and fibrinolysis. | Concurrent use significantly increases hemorrhagic risk; avoid if possible. |
| DOACs (rivaroxaban, apixaban, etc.) | Additive anticoagulant effect. Recent DOAC intake increases bleeding risk. | Assess when last dose was taken; may contraindicate thrombolysis. |
Commonly Co-Administered Agents
| Drug | Role in Treatment | Notes |
|---|---|---|
| Aspirin | Antiplatelet agent; prevents further clot formation. | Loading dose 150–300 mg given as soon as possible, then 75–100 mg daily. |
| Clopidogrel | Dual antiplatelet therapy; reduces recurrent events. | Loading dose 300 mg (75 mg if ≥75 years), then 75 mg daily. |
| Enoxaparin | Preferred LMWH for adjunctive anticoagulation. | IV bolus followed by subcutaneous injections. Dose-adjusted for age and renal function. |
Always inform your medical team about all medicines you are currently taking or have recently taken, including over-the-counter drugs, herbal supplements, and dietary supplements. This information is critical for safe thrombolytic therapy.
What Is the Correct Dosage of Metalyse?
Your doctor will calculate the appropriate dose based on your body weight. Metalyse is always given as a single intravenous bolus injection, which is a key advantage over older thrombolytics that required extended infusion times. The faster the drug is administered after the onset of chest pain, the better the outcome. Clinical evidence strongly supports the principle of “time is muscle” – earlier treatment preserves more heart tissue.
Adults – Weight-Based Dosing
| Body Weight | Dose (Units) | Dose (mg) | Volume to Inject (mL) |
|---|---|---|---|
| < 60 kg | 6,000 | 30 | 6 |
| 60 to < 70 kg | 7,000 | 35 | 7 |
| 70 to < 80 kg | 8,000 | 40 | 8 |
| 80 to < 90 kg | 9,000 | 45 | 9 |
| ≥ 90 kg | 10,000 | 50 | 10 |
The reconstituted solution contains 1,000 units (5 mg) per mL, making volume calculation straightforward. Metalyse is supplied as a lyophilised (freeze-dried) powder that is reconstituted with sterile water for injection using the provided pre-filled syringe and vial adapter.
Children
Metalyse is not recommended for children and adolescents under 18 years of age. There are no established paediatric dosing guidelines for tenecteplase in the treatment of myocardial infarction.
Elderly Patients
No dose adjustment is required for elderly patients based on age alone. However, patients aged 75 years and older have a significantly higher risk of bleeding complications, including intracranial hemorrhage. The decision to administer thrombolytic therapy in elderly patients requires careful individual risk-benefit assessment. The ASSENT-2 trial included patients up to age 75, and subgroup analyses in subsequent studies have informed current guideline recommendations for this age group.
Missed Dose
The concept of a missed dose does not apply to Metalyse, as it is a single-dose emergency treatment administered in hospital. If for any reason the injection is not given or is incomplete, your treating physician will determine the appropriate course of action based on the clinical situation.
Overdose
In the event of accidental overdose, the primary risk is excessive bleeding. There is no specific antidote for tenecteplase. Treatment of overdose is supportive, with management focused on controlling hemorrhage. Options include administration of fresh frozen plasma, tranexamic acid, or other procoagulant therapies as clinically indicated. The half-life of tenecteplase is approximately 20–24 minutes, which means the drug is cleared relatively quickly from the bloodstream.
What Are the Side Effects of Metalyse?
Like all medicines, Metalyse can cause side effects, although not everyone will experience them. The most significant risk is bleeding, which is inherent to the mechanism of action of thrombolytic drugs. The clinical team will closely monitor you throughout and after treatment for any signs of hemorrhage.
Side effects are categorised below by frequency. It is important to distinguish between side effects of the drug itself and complications related to the underlying heart attack and its treatment.
Side Effects Related to Metalyse
Very Common
Affects more than 1 in 10 patients
- Bleeding (at various sites)
Common
Affects up to 1 in 10 patients
- Bleeding at the injection site or puncture sites
- Nosebleeds (epistaxis)
- Urogenital bleeding (blood in urine)
- Bruising (ecchymosis)
- Gastrointestinal bleeding (e.g., bleeding from the stomach or intestines)
Uncommon
Affects up to 1 in 100 patients
- Reperfusion arrhythmias (irregular heartbeat), which may occasionally lead to cardiac arrest
- Retroperitoneal bleeding (internal bleeding in the abdomen)
- Cerebral hemorrhage (bleeding in the brain) – death or permanent disability may occur
- Eye bleeding (ocular hemorrhage)
Rare
Affects up to 1 in 1,000 patients
- Low blood pressure (hypotension)
- Pulmonary hemorrhage (bleeding in the lungs)
- Anaphylactoid reactions: rash, urticaria (hives), bronchospasm (breathing difficulty)
- Hemopericardium (bleeding into the pericardial sac)
- Pulmonary embolism and thrombotic embolisation in other organs
Not Known
Frequency cannot be estimated from available data
- Fat embolism
- Nausea and vomiting
- Increased body temperature (fever)
- Need for blood transfusion due to bleeding
Side Effects Related to the Heart Attack and/or Thrombolytic Therapy
The following events have been reported as consequences of the underlying myocardial infarction and/or thrombolytic treatment. They may be difficult to distinguish from the natural course of a heart attack:
Very Common
Affects more than 1 in 10 patients
- Low blood pressure (hypotension)
- Irregular heartbeat (arrhythmias)
- Chest pain (angina pectoris)
Common
Affects up to 1 in 10 patients
- Recurrent chest pain / recurrent ischaemia
- Reinfarction (another heart attack)
- Heart failure
- Cardiogenic shock
- Pericarditis (inflammation of the heart sac)
- Pulmonary oedema (fluid in the lungs)
Uncommon
Affects up to 1 in 100 patients
- Cardiac arrest
- Mitral valve insufficiency or pericardial effusion
- Venous thrombosis
- Cardiac tamponade (fluid compression of the heart)
- Myocardial rupture (tear in the heart muscle)
Rare
Affects up to 1 in 1,000 patients
- Pulmonary embolism
These cardiovascular events can be life-threatening and may result in death. In patients who experience cerebral hemorrhage, neurological side effects such as drowsiness (somnolence), speech disorders, hemiparesis (paralysis of one side of the body), and seizures (convulsions) have been reported.
It is important to report suspected adverse reactions after the medicine has been authorised. This allows ongoing monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients are encouraged to report adverse reactions through their national pharmacovigilance system (e.g., the Yellow Card Scheme in the UK, MedWatch in the US, or the EMA's EudraVigilance system in the EU).
How Should You Store Metalyse?
As a hospital medicine, Metalyse is stored and managed by healthcare professionals according to pharmaceutical storage protocols. However, the following information is provided for completeness and for healthcare professionals involved in stock management:
- Keep out of the sight and reach of children.
- Do not use after the expiry date printed on the label and carton (after “EXP”).
- Store at temperatures not exceeding 30°C.
- Keep in the original outer carton to protect from light.
- After reconstitution, the solution may be stored for up to 24 hours at 2–8°C or up to 8 hours at 30°C. However, for microbiological reasons, the reconstituted solution should normally be used immediately.
- Do not dispose of medicines via wastewater or household waste. Follow local pharmaceutical disposal guidelines to protect the environment.
What Does Metalyse Contain?
Metalyse is supplied as a lyophilised (freeze-dried) powder for reconstitution with the provided sterile water for injection. The product is available in two strengths:
- 40 mg vial: Contains 8,000 units of tenecteplase. Supplied with a pre-filled syringe containing 8 mL of solvent and a vial adapter. After reconstitution, each mL contains 1,000 units of tenecteplase.
- 50 mg vial: Contains 10,000 units of tenecteplase. Supplied with a pre-filled syringe containing 10 mL of solvent and a vial adapter. After reconstitution, each mL contains 1,000 units of tenecteplase.
Excipients (Inactive Ingredients)
- Arginine – amino acid used as a buffer/stabiliser
- Concentrated phosphoric acid (E 338) – pH adjusting agent
- Polysorbate 20 (E 432) – surfactant/stabiliser
- Water for injections – solvent (in pre-filled syringe)
Gentamicin is present as a trace residue from the manufacturing process. Individuals with known gentamicin allergy should inform their healthcare team prior to treatment.
Pack Contents
Each carton contains:
- One vial of freeze-dried powder (40 mg or 50 mg tenecteplase)
- One pre-filled syringe of sterile water for injection (8 mL or 10 mL)
- One vial adapter for reconstitution
The marketing authorisation holder is Boehringer Ingelheim International GmbH, Binger Strasse 173, 55216 Ingelheim am Rhein, Germany. The product is manufactured by Boehringer Ingelheim Pharma GmbH & Co. KG in Biberach, Germany, and Boehringer Ingelheim France in Paris, France.
Frequently Asked Questions About Metalyse
Both Metalyse (tenecteplase) and alteplase are thrombolytic agents used to dissolve blood clots, but they differ in key practical ways. Metalyse is given as a single bolus injection over 5–10 seconds, while alteplase requires a 90-minute intravenous infusion. Tenecteplase has higher fibrin specificity and a longer plasma half-life (20–24 minutes vs. 4–5 minutes for alteplase). The ASSENT-2 trial demonstrated equivalent 30-day mortality between the two drugs for heart attack treatment. The single-bolus administration of Metalyse makes it particularly advantageous in pre-hospital settings and busy emergency departments.
Metalyse begins dissolving the blood clot within minutes of injection. Coronary artery reperfusion (restoration of blood flow) typically occurs within 30–90 minutes after administration, though this varies depending on the size, age, and composition of the clot. Signs of successful reperfusion include resolution of chest pain, normalisation of ST-segment elevation on the ECG, and the occurrence of reperfusion arrhythmias (which, paradoxically, are a sign that blood flow has been restored). Early administration is crucial – treatment within the first 2 hours of symptom onset yields the best outcomes.
Yes, one of the major advantages of Metalyse over older thrombolytics is its suitability for pre-hospital administration. Because it requires only a single IV bolus injection (rather than a prolonged infusion), it can be safely administered by trained paramedics or emergency physicians in the ambulance. Pre-hospital thrombolysis with tenecteplase has been shown to significantly reduce time-to-treatment and improve outcomes, particularly in rural and remote areas where transfer to a PCI-capable hospital may take a long time. The STREAM trial demonstrated that a pharmacoinvasive strategy (pre-hospital tenecteplase followed by angiography) was equivalent to primary PCI in early presenters.
After receiving Metalyse, you will be closely monitored in a coronary care unit or intensive care setting. Continuous ECG monitoring, regular blood pressure checks, and neurological assessments are standard. Most patients will undergo coronary angiography within 2–24 hours after successful thrombolysis to assess the coronary arteries and determine whether a stent (PCI) is needed. This approach is called a “pharmacoinvasive strategy.” If thrombolysis fails to restore blood flow (indicated by persistent chest pain and ST-segment elevation), urgent “rescue PCI” is performed. Anticoagulant and antiplatelet therapy continues after thrombolysis.
Yes, tenecteplase is increasingly being investigated and used for acute ischemic stroke. Several large randomised controlled trials have compared tenecteplase with alteplase for stroke. The EXTEND-IA TNK trial (2018) showed tenecteplase was superior to alteplase for achieving reperfusion before thrombectomy. The AcT trial (2022) confirmed non-inferiority of tenecteplase to alteplase for functional outcomes in stroke. A dose of 0.25 mg/kg (lower than the cardiac dose) is typically used for stroke. While the approved indication for Metalyse remains acute myocardial infarction, many stroke centres now use tenecteplase off-label based on this growing body of evidence.
Re-administration of Metalyse is not routinely recommended. If a patient has received tenecteplase previously and has another heart attack, the physician will exercise particular caution and consider the risks of repeat thrombolytic therapy, including the potential for antibody formation against tenecteplase. In practice, most patients who present with a second STEMI are treated with primary PCI rather than repeat thrombolysis, especially if catheterisation facilities are available. The decision is always made on an individual basis by the treating cardiologist or emergency physician.
References
- Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999;354(9180):716-722. doi:10.1016/S0140-6736(99)07403-6
- 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. Eur Heart J. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393
- Armstrong PW, Gershlick AH, Goldstein P, et al. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction (STREAM trial). N Engl J Med. 2013;368(15):1379-1387. doi:10.1056/NEJMoa1301092
- Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke (EXTEND-IA TNK). N Engl J Med. 2018;378(17):1573-1582. doi:10.1056/NEJMoa1716405
- Menon BK, Buck BH, Singh N, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022;400(10347):161-169. doi:10.1016/S0140-6736(22)01054-6
- European Medicines Agency. Metalyse – Summary of Product Characteristics. EMA/EPAR. Available at: https://www.ema.europa.eu/
- World Health Organization. WHO Model List of Essential Medicines. 23rd List, 2023. Geneva: WHO; 2023.
- National Institute for Health and Care Excellence (NICE). Acute coronary syndromes. NICE guideline [NG185]. 2020, updated 2023.
- O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. J Am Coll Cardiol. 2013;61(4):e78-e140. doi:10.1016/j.jacc.2012.11.019
- Boehringer Ingelheim. Metalyse (tenecteplase) Prescribing Information / Package Leaflet. Ingelheim am Rhein, Germany.
Editorial Team
Written by the iMedic Medical Editorial Team – specialists in cardiology, emergency medicine, and clinical pharmacology with documented academic backgrounds and clinical experience.
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