Alteplase (Activase, Cathflo)

Emergency & Prehospital

• Acute ischemic stroke (AIS): The US label covers a disabling deficit that starts within 3 hr of symptom onset. Noncontrast CT has to rule out hemorrhage first. The 3 to 4.5 hr window is off-label, though the ECASS III trial tested it. EMS: write down the last-known-well time. Notify the receiving stroke center early, so routing and prenotification follow the regional stroke system.
• Massive pulmonary embolism (PE): The label covers obstruction of a lobe or several segments with unstable hemodynamics. "Massive" is the label's term. The 2026 AHA/ACC PE guideline sorts patients into its own clinical categories. Map your patient to the category your PE protocol uses. Reduced-dose and catheter-directed options exist, and both depend on the protocol.
• Acute myocardial infarction (AMI): The label names two goals: reducing mortality and reducing heart failure. Watch the warning, though. When the patient is at low risk of death from cardiac causes, the label says stroke risk may outweigh the benefit.
• Cardiac arrest with confirmed or suspected PE: AHA 2025 Part 10 covers fibrinolysis during CPR. The regimen and CPR duration are set per local protocol and by the PE response team.

ED / ICU / Transport

• Stroke at 3 to 4.5 hr: This is off-label under the US label, whose window is within 3 hr. In ECASS III (821 patients, 3 to 4.5 hr), 52.4% had a favorable outcome with alteplase against 45.2% with placebo. Symptomatic intracranial hemorrhage ran 2.4% against 0.2%. The 2026 AHA/ASA guideline replaces the 2018 and 2019 guidance. The 2019 AHA/ASA guideline supported IV alteplase within 4.5 hr for eligible patients. The 2026 AHA/ASA guideline is the current version, and it updates thrombolytic choice (alteplase vs tenecteplase). The stroke protocol sets eligibility. See the tenecteplase page.
• Stroke at 4.5 to 9 hr with salvageable tissue: Off-label. EXTEND used perfusion imaging to select patients. The trial stopped at 225 of 310 planned patients. Symptomatic hemorrhage was 6.2% against 0.9%. Only a stroke expert should make this call.
• Intermediate-risk PE: Routine lysis is not indicated. PEITHO tested tenecteplase, not alteplase. Fibrinolysis reduced death or hemodynamic decompensation (2.6% vs 5.6%). It also increased major hemorrhage and stroke.

Other Uses

• Occluded central venous access device: Cathflo Activase 2 mg instilled into the lumen restores catheter function. It is not for systemic lysis.
• Pleural infection (off-label): The MIST2 trial studied intrapleural tPA with DNase. There is no labeled dose or use. Follow the pleural service protocol.

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• Activase 50 mg and 100 mg single-dose vials: lyophilized powder with 50 mL or 100 mL Sterile Water for Injection; reconstitutes to 1 mg/mL (50 mg with 50 mL; 100 mg with 100 mL).
• Cathflo Activase 2 mg vial: lyophilized powder; add 2.2 mL Sterile Water for Injection (not supplied) for 1 mg/mL.
• Stock fit: The 100 mg vial covers the PE dose. Any stroke dose above 50 mg (patients over about 56 kg) needs the 100 mg vial or more than one vial.

Adult Dosing

Pediatric Dosing

Preparation & Administration

• Reconstitution, 50 mg vial (has vacuum): DO NOT USE IF VACUUM IS NOT PRESENT. Use only the supplied preservative-free Sterile Water for Injection, never bacteriostatic water. Reconstitute with an 18-gauge or other large-bore needle and syringe, directing the Sterile Water stream into the lyophilized cake (50 mL for 50 mg). Let slight foam settle.
• Reconstitution, 100 mg vial (no vacuum): use the supplied transfer device and the kit Instructions for Use (100 mL preservative-free Sterile Water). Do not push air into the vial, and insert needles only through the center ring of the stopper. Do not use bacteriostatic water.
• Dilution (optional): 1 mg/mL may be diluted to 0.5 mg/mL in an equal volume of 0.9% sodium chloride or 5% dextrose, in a PVC bag or glass.
• Bolus: draw the bolus from the reconstituted vial or from a port on the primed line, or program the pump to deliver it at the start of the infusion. Do not prime the syringe with air.
• Infusion: run on a pump. Do not add any other medication to infusion solutions containing alteplase.
• Stability: use within 8 hours of reconstitution at 2–30 °C (36–86 °F). No preservative. Discard unused solution.
• Line and punctures: avoid intramuscular injections and internal jugular or subclavian punctures. If extravasation occurs, stop the infusion at that site and apply local therapy. If an arterial puncture is unavoidable, use a compressible upper-extremity site and hold pressure for at least 30 minutes.
• Cathflo: add 2.2 mL Sterile Water for Injection, swirl gently (do not shake) until dissolved within 3 minutes, use within 8 hours, withdraw 2 mL (2 mg) and instill without force. Add no other medication.

Contraindications

• Stroke: current intracranial hemorrhage; subarachnoid hemorrhage; active internal bleeding; intracranial or intraspinal surgery or serious head trauma within 3 months; intracranial conditions that raise bleeding risk (some neoplasms, arteriovenous malformations, aneurysms); bleeding diathesis; current severe uncontrolled hypertension
• AMI or PE: active internal bleeding; history of recent stroke; intracranial or intraspinal surgery or serious head trauma within 3 months; intracranial conditions that raise bleeding risk; bleeding diathesis; current severe uncontrolled hypertension
• Hypersensitivity: known hypersensitivity to alteplase (Cathflo)

Precautions

• Bleeding risk (label): recent major surgery, obstetric delivery, organ biopsy or puncture of a noncompressible vessel; recent GI or GU bleeding; recent trauma; recent intracranial hemorrhage; cerebrovascular disease; systolic BP above 175 or diastolic above 110 mmHg (AMI and PE label list; not the stroke threshold); acute pericarditis; subacute bacterial endocarditis; hemostatic defects from severe hepatic or renal disease; pregnancy; diabetic hemorrhagic retinopathy; advanced age; current anticoagulant use
• Anticoagulants and antiplatelets: These raise bleeding risk. In stroke, concomitant heparin and aspirin in the first 24 hours has not been studied.
• Traumatic intubation: Fatal hemorrhage after traumatic intubation has been reported with alteplase. Label 5.1 also asks that stroke treatment happen only at facilities that can manage intracranial hemorrhage promptly.
• Hypersensitivity and angioedema: Urticaria, anaphylactoid reactions, laryngeal edema and shock have all occurred. Angioedema can start during the infusion and last up to 2 hours after it. Many cases involved ACE inhibitor use.
• Left-heart thrombus: Mitral stenosis or atrial fibrillation carries a thromboembolism risk. In PE, lysing a deep venous thrombus can cause re-embolization.
• Cholesterol embolization: Watch for livedo reticularis, purple toes and acute kidney injury. It can be fatal.
• Catheter (Cathflo): An infected catheter may send infection into the circulation. Avoid vigorous suction and excessive instillation pressure. Trials left out hemodialysis catheters and known mechanical occlusion.

Hold / Reassess If

• Before the stroke bolus (label): Discontinue if pretreatment INR is over 1.7 or aPTT is elevated (label 2.1). Treatment may start before coagulation results come back only in patients with no recent oral anticoagulant or heparin use. The trials also stopped treatment for PT over 15 seconds.
• Before the stroke bolus (protocol checks, not in the label): AHA/ASA 2019 eligibility criteria list blood glucose under 50 mg/dL (a contraindication unless symptoms fully resolve after glucose correction); platelet count under 100,000/mm³; therapeutic LMWH within 24 hr; DOAC within 48 hr (a protocol may allow this when renal function and coagulation tests are normal); heparin with an elevated aPTT. The 2026 guideline revised the thrombolysis contraindications. The current stroke protocol governs these thresholds.
• Blood pressure: before the bolus, BP above 185/110 mmHg: treat with IV antihypertensives and recheck; if it cannot be brought to 185/110 mmHg or lower, do not give alteplase. After the bolus, the AHA/ASA 2019 target is below 180/105 mmHg for at least 24 hr (secondary-source confirmation; primary table to be checked). The label's trial used 185/110 mmHg for 24 hr (label 14.1). That is a trial description, not the guideline target. The stroke protocol sets the target.
• During or after the infusion: severe headache, vomiting, acute hypertension, falling consciousness or a new deficit: stop the infusion and obtain STAT noncontrast CT.
• Serious bleeding: terminate the infusion and start the bleeding steps; stop heparin and antiplatelet agents per protocol.
• Swelling of tongue, lips or airway, urticaria or stridor: stop the infusion, airway first, then antihistamine, IV corticosteroid and epinephrine per protocol.
• After stroke treatment: The trials gave no anticoagulant or antiplatelet agent in the first 24 hours. The label says concomitant heparin and aspirin in that window has not been studied. The stroke team starts antithrombotics once follow-up imaging rules out hemorrhage. Neuro-check frequency is set by protocol. Labetalol or nicardipine may be used per protocol (labetalol, nicardipine).
• Catheter: a second dose only if function is not restored at 120 min; never exceed 2 doses (4 mg).

Common

• Bleeding is the most frequent adverse reaction across all approved indications (above 5% in the label), puncture-site bleeding included.
• Hypersensitivity: urticaria and rash; anaphylactoid reactions are less common
• After AMI treatment: arrhythmias and AV block (post-marketing reports)
• Catheter use: venous thrombosis and catheter-related sepsis reported in the Cathflo trials

Serious / Life-Threatening

Overdose & Toxicity Management

• Risk: Doses above the labeled limits raise bleeding risk. In AMI, doses of 150 mg or more are associated with more intracranial bleeding.
• Antidote: There is no specific one. Stop the infusion. Bleeding can keep going for hours to days after the drug clears.
• Bleeding support (confirm with pharmacy and the stroke team): cryoprecipitate 10 units IV over 10 to 30 min, repeated to keep fibrinogen at 150 mg/dL or higher (some protocols use 200 mg/dL); platelet transfusion per protocol if the platelet count is under 100,000/mm³; an antifibrinolytic (tranexamic acid or aminocaproic acid) per the stroke protocol, which sets the agent and dose (off-label for this use; see tranexamic acid); protamine if heparin is infusing. See fibrinogen for the product.
• Report: File a medication-error report. Review the weight-based dose and the pump programming.

Clinically Significant Interactions

IV Compatibility

• Diluent: reconstitute with the supplied Sterile Water for Injection only; optional dilution to 0.5 mg/mL in 0.9% sodium chloride or 5% dextrose
• Additives: no other drug in the alteplase solution or bag
• Containers: PVC bag or glass vial and infusion set
• Use window: within 8 hours of reconstitution, at 2–30 °C; no antibacterial preservative

Check compatibility against an institutional resource.

• Pediatrics: Systemic use is not established in children. See the Pediatric Dosing table. Pediatric stroke or PE decisions are made by pediatric specialists working with the stroke or PE team. Cathflo was studied in 432 patients under 17 years. Serious adverse event rates were similar to adults.
• Neonates: There are no systemic dosing data. The Cathflo trials included children from 2 weeks of age.
• Pregnancy: Human data are insufficient. In rabbits, alteplase was embryocidal at doses near the human AMI exposure. Pregnancy is also listed as a bleeding-risk factor. Pregnancy-associated stroke or PE needs a joint decision from obstetrics and the stroke or PE team. Use it only when the benefit justifies the risk.
• Lactation: There are no data on passage into human milk or effects on the infant. Decide with the team.
• Older Adults: In exploratory stroke analyses, age over 77 was associated with more intracranial hemorrhage. In the AMI trial, patients over 75 made up 12% of enrollment.
• Renal Impairment: No specific dose adjustment has been established. Severe renal disease with hemostatic defects counts as a bleeding precaution.
• Hepatic Impairment: Significant hepatic dysfunction is a bleeding precaution. The liver is the main clearance route.
• Obesity / Dosing Weight: The stroke dose is per kg, capped at 90 mg. The label does not say which weight it uses. The AMI regimen has a weight band at 67 kg. Use the weight the protocol specifies.

• Scope: Stroke and PE thrombolysis usually start in emergency departments, stroke centers and ICUs, under stroke or PE team direction. Prehospital use varies by state and agency protocol.
• Storage & Stability: lyophilized Activase at room temperature not above 30 °C (86 °F) or refrigerated at 2–8 °C (36–46 °F), protected from light. Cathflo is refrigerated at 2–8 °C. Reconstituted product: use within 8 hr at 2–30 °C.
• Carried Concentration: Reconstituted alteplase is 1 mg/mL. Cathflo is also 1 mg/mL, but it is for catheters only. Never give the catheter product IV.
• Infusions in Transport: Stroke: 10% bolus, then 90% over 60 min on a pump. PE: 100 mg over 2 hr. Check the bag volume for the trip, the pump rate and the bolus already given. Do not add drugs to the bag. Watch the infusion site for extravasation.
• Handoff Essentials: drug and mg dose, weight used, last known well or symptom onset, bolus and infusion start times, BP and neuro trend, anticoagulants and antiplatelets given, any swelling or bleeding.

Mechanism of Action

• Target: Alteplase binds fibrin in a thrombus. It converts the plasminogen trapped there into plasmin.
• Effect: Plasmin cuts the fibrin apart, which lyses the clot and restores flow. Without fibrin, little conversion happens, so systemic proteolysis stays limited at pharmacologic concentrations.
• Consequence: Fibrinogen falls 16–36% after a 100 mg dose. That drop adds to the bleeding risk.
• Catheter use: The same enzyme works inside the catheter lumen. Systemic levels are not expected to reach pharmacologic range.

Pharmacokinetics

• Half-life: The initial half-life is under 5 minutes. The terminal half-life is about 72 minutes (Cathflo label, after a 100 mg accelerated AMI infusion over 90 min).
• Metabolism / Elimination: Mainly hepatic. Plasma clearance runs 380–570 mL/min.
• Distribution: At first, the volume of distribution approximates plasma volume.

Generic Name

Alteplase (AL-te-plase)

Brand Names

Activase (US); Cathflo Activase (catheter clearance)

Pharmacologic Class

Plasminogen activator (recombinant tissue plasminogen activator)

Therapeutic Class

Thrombolytic (fibrinolytic) agent

Controlled Substance

Not controlled

ISMP High-Alert

Yes: ISMP high-alert medication (thrombolytic agents)

Look-Alike / Sound-Alike

Activase / TNKase (tenecteplase); alteplase / tenecteplase

Error-Prone Abbreviations to Avoid

"tPA", "TNK", "rt-PA": write the generic name