Alteplase

Alteplase is a prescription medication used to treat the symptoms of Acute Myocardial Infarction, Pulmonary Embolism, Acute Ischemic Stroke, and Central Venous Catheter Occlusion.  

• Alteplase is available under the following different brand names: Activase, TPA, Cathflo Activase 

Adult and Pediatric dosage

Powder for injection (reconstitute before use)

• 2mg (Cathflo Activase)
• 50mg (Activase)
• 100mg (Activase)

Acute Myocardial Infarction

Adult dosage

• Recommended total dose for AMI is based on patient weight, not to exceed 100 mg, regardless of the selected administration regimen (accelerated or 3 hr).
• Accelerated infusion (1-1/2 hour)
• Patients weighing 67 kg or less: 15 mg IVP bolus over 1-2 minutes, then 0.75 mg/kg IV infusion over 30 minutes (not to exceed 50 mg), and then 0.5 mg/kg IV over next 60 minutes (not to exceed 35 mg over 1 hour)
• Patients weighing over 67 kg (100 mg total dose infused over 1.5 hour): 15 mg IVP bolus over 1-2 minutes, then 50 mg IV infusion over next 30 minutes, and then remaining 35 mg over next 60 minutes
• 3-hour infusion
• Patients weighing less than 65 kg: 0.075 mg/kg IVP bolus over 1-2 minutes, then 0.675 mg/kg infused over the rest of the first hour, then 0.25 mg/kg IV for the next 2 hours
• Patients weighing 65 kg or more: (100 mg total dose infused over 3 hours): 6-10 mg IVP bolus over 1-2 minutes, then 50-54 mg infused over the rest of the first hour (ie, 60 mg in 1st hour including 6-10 mg bolus), THEN 20 mg/hour for the next 2 hour

Pulmonary Embolism

Adult dosage

• 100 mg IV infused over 2 hours; institute parenteral anticoagulation near the end of or immediately following alteplase infusion when the PTT or thrombin time returns to greater than 2x normal

Acute Ischemic Stroke

Adult Dosage

• 0.9 mg/kg IV; not to exceed 90 mg total dose; administer 10% of the total dose as an initial IV bolus over 1 minute and the remainder infused over 60 minutes

Central Venous Catheter Occlusion

Adult Dosage

• Cathflo Activase: 2 mg in 2 mL instilled into occluded catheter

Pediatric Dosage

• Children weighing less than 30 kg: Cathflo Activase: Instill 110% of the internal lumen volume of the catheter; not to exceed 2 mg in 2 mL
• Children weighing more than 30 kg: Cathflo Activase: 2 mg instilled into occluded catheter

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”.

Common side effects of Alteplase include:

• bleeding

Serious side effects of Alteplase include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• any bleeding that will not stop, 
• sudden headache, 
• weakness, 
• dizziness, 
• bleeding gums, 
• nosebleeds, 
• easy bruising, 
• bleeding from a wound, incision, catheter, or needle injection, 
• bloody or tarry stools, 
• coughing up blood, 
• vomit that looks like coffee grounds, 
• red or pink urine, 
• heavy menstrual periods, 
• abnormal vaginal bleeding, 
• sudden numbness or weakness (especially on one side of the body), 
• slurred speech, 
• problems with vision or balance, 
• chest pain or heavy feeling, 
• pain spreading to the jaw or shoulder, 
• nausea, 
• sweating, 
• general ill feeling, 
• swelling, 
• rapid weight gain, 
• little or no urination, 
• severe stomach pain, 
• vomiting, 
• darkening or purple discoloration of fingers or toes, 
• very slow heartbeats, 
• shortness of breath, 
• lightheadedness, 
• sudden severe back pain, 
• muscle weakness, 
• numbness or loss of feeling in the arms or legs, 
• severe headache, 
• blurred vision, 
• pounding in the neck or ears, 
• anxiety, 
• nosebleed, and
• severe pain in the upper stomach spreading to the back

Rare side effects of Alteplase include:

• none 

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first

Alteplase has severe interactions with the following drugs:

• defibrotide
• prothrombin complex concentrate, human

Alteplase has serious interactions with the following drugs:

• apixaban
• zanubrutinib

Alteplase has moderate interactions with at least 72 other drugs.

Alteplase has minor interactions with the following drugs:

• ceftaroline  

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drugs interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

Acute Ischemic Stroke

• Do not administer to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit
• Current or prior intracranial hemorrhage
• Subarachnoid hemorrhage suspected
• Active internal bleeding
• Stroke within 3 months
• Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
• Presence of intracranial conditions that may increase the risk of bleeding (eg, some neoplasms, arteriovenous malformations, aneurysms)
• Bleeding diathesis
• Current severe uncontrolled hypertension

Acute myocardial infarction or pulmonary embolism

• Do not administer for treatment of AMI or PE in the following situations in which the risk of bleeding is greater than the potential benefit
• Active internal bleeding
• History of recent stroke
• Ischemic stroke within 3 months except when within 4.5 hours
• Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma
• Presence of intracranial conditions that may increase the risk of bleeding (eg, some neoplasms, arteriovenous malformations, aneurysms)
• Significant closed head or facial trauma with radiographic evidence of brain injury or facial trauma within 3 months
• Bleeding diathesis
• Aortic dissection
• Current severe uncontrolled hypertension
• Prior intracranial hemorrhage

Effects of drug abuse

• None

Short-Term Effects

• See “What are Side Effects Associated with Using Alteplase?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Alteplase?”

Cautions

• Catheter dysfunction may be caused by a variety of conditions other than thrombus formation, such as catheter malposition, mechanical failure, constriction by a suture, and lipid deposits or drug precipitates within the catheter lumen; considers these types of conditions before administering treatment
• Because of risk of damage to vascular wall or collapse of soft-walled catheters, vigorous suction should not be applied during attempts to determine catheter occlusion
• Avoid applying excessive pressure when agent is instilled into catheter; such force could cause rupture of catheter or expulsion of clot into circulation
• Use caution in recent major surgery, cerebrovascular disease, HTN, acute pericarditis, hemostatic defects, severe thrombophlebitis, severe hepatic/renal dysfunction
• Hypersensitivity, including urticaria, angioedema and anaphylaxis, reported in association with therapy; monitor patients during and for several hours after infusion for hypersensitivity; if signs of hypersensitivity occur, e.g. anaphylactoid reaction or angioedema develops, discontinue therapy and promptly institute appropriate therapy
• Monitor patients during and for several hours after infusion for orolingual angioedema; discontinue therapy if angioedema develops
• Cholesterol embolism reported rarely in patients treated with thrombolytic agents; may present with pancreatitis, cerebral infarction, acute renal failure, gangrenous digits, hypertension, rhabdomyolysis, or retinal artery occlusion
• Consider risk of re-embolization from lysis of underlying deep venous thrombi in patients with pulmonary embolism
• Internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, respiratory) or external bleeding, especially at arterial and venous puncture sites may occur
• Avoid intramuscular injections and trauma to patient while on therapy
• Perform venipunctures carefully and only as required
• Minimize bleeding from noncompressible sites by avoiding internal jugular and subclavian venous punctures
• If arterial puncture necessary during therapy infusion, use upper extremity vessel that is accessible to manual compression, apply pressure for at least 30 min, and monitor puncture site closely
• Patients treated for acute ischemic stroke, with high risk of intracranial hemorrhage, should be treated at facilities that can provide timely access to appropriate evaluation and management of intracranial hemorrhage
• Coronary thrombolysis may result in reperfusion arrhythmias
• Patients who present within 3 hours of stroke symptom onset, should be treated with alteplase unless contraindications exist; longer time window (3-4.5 hours after symptom onset) shown to be safe and efficacious for select individuals; treatment of patients with minor neurological symptoms not recommended
• Alteplase does not treat adequately underlying deep vein thrombosis in patients with pulmonary embolism; consider possible risk of re-embolization due to lysis of underlying deep venous thrombi in this setting
• Use with caution in presence of known or suspected infection in catheter; using agent in patients with infected catheters may release a localized infection into the systemic circulation; as with all catheterization procedures, use care to maintain aseptic technique

Bleeding

• Agent has not been studied in patients known to be at risk for bleeding events that may be associated with use of thrombolytics; exercise caution with patients who have active internal bleeding or who have had any of the following within 48 hours: surgery, obstetrical delivery, percutaneous biopsy of viscera or deep tissues, or puncture of non-compressible vessels
• Exercise caution with patients who have thrombocytopenia, other hemostatic defects (including those secondary to severe hepatic or renal disease), or any condition for which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location, or who are at high risk for embolic complications (e.g., venous thrombosis in the region of the catheter)
• Death and permanent disability reported in patients who have experienced stroke and other serious bleeding episodes when receiving pharmacologic doses of a thrombolytic
• Should serious bleeding in a critical location (e.g., intracranial, gastrointestinal, retroperitoneal, pericardial) occur, therapy should be stopped and the drug should be withdrawn from the catheter
• Clinical conditions that increase risk of bleeding for all indications
• Recent major surgery or procedure, (e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels)
• Cerebrovascular disease or recent intracranial hemorrhage
• Recent gastrointestinal or genitourinary bleeding
• Recent trauma
• Hypertension: systolic BP above 175 mm Hg or diastolic BP above 110 mm Hg
• High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
• Acute pericarditis
• Subacute bacterial endocarditis
• Hemostatic defects including those secondary to severe hepatic or renal disease
• Significant hepatic dysfunction
• Pregnancy
• Diabetic hemorrhagic retinopathy, or other hemorrhagic ophthalmic conditions or patients currently receiving anticoagulants (e.g., warfarin sodium)
• Septic thrombophlebitis or occluded AV cannula at seriously infected site ⋅
• Advanced age
• Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location

Pregnancy and Lactation

• Published studies and case reports on alteplase use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes; alteplase is embryocidal in rabbits when intravenously administered during organogenesis at clinical exposure for AMI, but no maternal or fetal toxicity was evident at lower exposure in pregnant rats or rabbits; the most common complication of thrombolytic therapy is bleeding; pregnancy may increase this risk; drug should be used during pregnancy only if potential benefit justifies potential risk to fetus.
• There are no data on presence of alteplase in human milk, effects on breastfed infant, or on milk production.