Dosing and uses of Activase, TPA (alteplase)
Adult dosage forms and strengths
powder for injection (reconstitute before use)
- 2mg (Cathflo Activase)
- 50mg (Activase)
- 100mg (Activase)
Acute Myocardial Infarction
Administer as soon as possible after onset of symptoms
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 hr)
- ≤67 kg: 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 hr)
- >67 kg (100 mg total dose infused over 1.5 hr): 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-hr infusion
- <65 kg: 0.075 mg/kg IVP bolus over 1-2 minutes, THEN 0.675 mg/kg infused over the rest of the first hr, THEN 0.25 mg/kg IV for the next 2 hr
- ≥65 kg: (100 mg total dose infused over 3 hr): 6-10 mg IVP bolus over 1-2 minutes, THEN 50-54 mg infused over the rest of the first hr (ie, 60 mg in 1st hr including 6-10 mg bolus), THEN 20 mg/hr for the next 2 hr
Pulmonary Embolism
100 mg IV infused over 2 hr; institute parenteral anticoagulation near the end of or immediately following alteplase infusion when the PTT or thrombin time returns to <2x normaL
Acute Ischemic Stroke
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
Dosing considerations (acute ischemic stroke)
- Exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment (see Contraindications)
- Administer as soon as possible but within 3 hr after onset of symptoms
- Monitor and control blood pressure during and following administration
- In patients without recent use of oral anticoagulants or heparin, treatment can be initiated prior to the availability of coagulation study results
- Discontinue if the pretreatment INR is >1.7 or the aPTT is elevated
Central Venous Catheter Occlusion
Cathflo Activase: 2 mg in 2 mL instilled into occluded catheter
Assess catheter function after 30 minutes of dwell time by attempting to aspirate blood; if unable to aspirate after 120 minutes dwell time, a 2nd dose may be administered and the process repeated
If catheter function restored, aspirate 4-5 mL blood to remove Cathflo Activase and residual clot
Gently irrigate with 0.9% NaCL
Arterial Thrombosis & Embolism (Off-label)
0.05-0.1 mg/kg/hr by transcatheter intra-arterial infusion for 1-8 hours or until lysis of thrombus
Intracerebral Hemorrhage (Orphan)
Treatment of intraventricular hemorrhage associated with intracerebral hemorrhage
Orphan indication sponsor
- Daniel F Hanley, MD; Johns Hopkins University, 600 N Wolfe St, Jefferson 1-109; Baltimore, MD 21287
Bronchitis (Orphan)
Orphan designation for treatment of plastic bronchitis
Sponsor
- Kathleen A Stringer, PharmD, FCCP - Professor; University of Michigan; 428 Church St; Ann Arbor, MI 48109-1065
Pediatric dosage forms and strengths
powder for injection (reconstitute before use)
- 2mg (Cathflo Activase)
Central Venous Catheter Occlusion
<30 kg
- Cathflo Activase: Instill 110% of the internal lumen volume of the catheter; not to exceed 2 mg in 2 mL
≥30 kg
- Cathflo Activase: 2 mg instilled into occluded catheter
- Assess catheter function after 30 minutes of dwell time by attempting to aspirate blood; if unable to aspirate after 120 minutes dwell time, a 2nd dose may be administered and the process repeated
- If catheter function restored, aspirate 4-5 mL blood in patients 10 kg or more (aspirate 3 mL if <10 kg) to remove Cathflo Activase and residual clot
- Gently irrigate with 0.9% NaCl
Activase, TPA (alteplase) adverse (side) effects
1-10%
Stroke (1.6%)
Frequency not defined
Accelerated idioventricular rhythm
Pulmonary edema
Arterial embolism
Bruising
Bleeding
DVt
Hypotension
Intracranial hemorrhage
GI/GU hemorrhage
Pulmonary embolism
Fever/chills
Nausea/vomiting
Sensitivity reaction
Sepsis
Shock
Warnings
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 intracranial hemorrhage
- Subarachnoid hemorrhage
- Active internal bleeding
- 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
- 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
Cautions
Use caution in recent major surgery, cerebrovascular disease, HTN, acute pericarditis, hemostatic defects, severe thrombophlebitis, severe hepatic/renal dysfunction
Avoid intramuscular injections
Monitor for bleeding; discontinue therapy if serious bleeding occurs
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
Consider risk of reembolization 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 hr of stroke symptom onset, should be treated with alteplase unless contraindications exist; longer time window (3-4.5 hr after symptom onset) shown to be safe and efficasious for select individuals; treatment of patients with minor neurological symptoms not recommended
Alteplase does not treat adequately underlying deep vein thromposis in patients with pulmonary embolism; consider possible risk of re-embolization due to lysis of underlying deep venous thrombi in this setting
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
Pregnancy category: C
Lactation: Excretion in milk unknown; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Activase, TPA (alteplase)
Mechanism of action
Recombinant human tissue-type plasminogen activator (t-PA); produces local fibrinolysis
Promotes thrombolysis by converting plasminogen to plasmin; plasmin degrades fibrin and fibrinogen
Absorption
Onset: Coronary thrombolysis occurs in 30 min; reaches peak response at 60 min
Peak plasma time: 20-40 min
Distribution
Vd: 27-53 L
Metabolism
Rapidly cleared from circulation by liver
Metabolites: Degradation products (constituent amino acids of alteplase)
Elimination
Initial half-life: 5 minutes (free, unbound form)
Terminal half-life: 72 minutes
Total body clearance: 34.3-38.4 mL/hr
Excretion: Urine
Administration
Vial Reconstitution
Use only the accompanying sterile water for injection (without preservatives); do not use bacteriostatic water for injection
Reconstitute using aseptic technique
Do not add other medication to resulting solution
Reconstitute no more than 8 hr before use (does not contains antibacterial preservatives)
Slight foaming is not unusual; let stand undisturbed for several minutes to allow large bubbles to dissipate
Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit
Activase may be administered as reconstituted at 1 mg/mL or further diluted immediately before administration in an equal volume of 0.9% NaCl or D5W, to yield a concentration of 0.5 mg/mL, using either PVC bags or glass vials
Avoid excessive agitation during dilution; mix by gently swirling and/or slow inversion
50-mg vials
- Do not use if vacuum is not present
- Using a large bore needle (eg, 18 gauge) and a syringe, reconstitute by adding the contents of the accompanying 50 mL vial of sterile water for injection (SWFI) to the 50 mg vial, directing the SWFI stream into the lyophilized cake
100-mg vials
- The 100 mg vials do not contain vacuum
- Using the transfer device provided, reconstitute by adding the contents of the accompanying 100 mL vial of SWFI to the 100 mg vial
- 1. Use aseptic technique
- 2. Remove the protective flip-caps from 1 vial of Activase and 1 vial of SWFI
- 3. Open the package containing the transfer device by peeling the paper label off the package
- 4. Remove the protective cap from 1 end of the transfer device and keeping the vial of SWFI upright, insert the piercing pin vertically into the center of the stopper of the vial of SWFI
- 5. Remove the protective cap from the other end of the transfer device; do NOT invert the vial of SWFI
- 6. Hold the vial of Activase upside down, position it so that the center of the stopper is directly over the exposed piercing pin of the transfer device, and push the vial of Activase down so that the piercing pin is inserted through the center of the Activase vial stopper
- 7. Invert the 2 vials so that the vial of Activase is on the bottom (upright) and the vial of SWFI is upside-down, allowing the SWFI to flow down through the transfer device; allow the entire contents of the vial of SWFI to flow into the Activase vial (approximately 0.5 mL of SWFI will remain in the diluent vial)
- 8. Remove the transfer device and the empty SWFI vial from the Activase vial and discard
- 9. Swirl gently to dissolve the Activase powder; do NOT shake
Bolus Dose Preparation
Prepare the bolus dose in 1 of the following ways
50-mg vials
- Remove the appropriate volume from the reconstituted vial (1 mg/mL) using a syringe and needle
- If this method is used with the 50 mg vials (contains vacuum), the syringe should not be primed with air and the needle should be inserted into the vial stopper
100-mg vials
- If the 100 mg vial (no vacuum) is used, the needle should be inserted away from the puncture mark made by the transfer device
- Remove the appropriate volume from a port (second injection site) on the infusion line after the infusion set is primed
- Program an infusion pump to deliver the appropriate volume as a bolus at the initiation of the infusion
Cathflo Activase preparation
Reconstitute 2 mg vial by adding 2.2 mL SWI (do not use bacteriostatic water for injection); yields final concentration of 1 mg/mL
Mix by gently swirling until completely dissolved; complete dissolution occurs within 3 minutes; do NOT shake
Use within 8 hr if stored at room temperature
