Activase

Catheter Occlusion Management Fibrinolytics
Vascular Occlusion Management Fibrinolytics

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Reconstitution
Reconstitute only with the provided Sterile Water for Injection to a final concentration of 1 mg/mL.
50-mg vials: Do not use if the vacuum is not present. Using a large-bore needle (e.g., 18-gauge) and a syringe, add the accompanying Sterile Water for Injection to the alteplase vial. Direct the stream of water into the lyophilized cake.
100-mg vials: Vials do not contain a vacuum. With the vial of Sterile Water for Injection upright, insert the piercing pin of the transfer device (provided) vertically into the center of the stopper. Hold the vial of alteplase upside-down over the piercing pin of the transfer device and push down so that the piercing pin is inserted through the center of the vial stopper. Invert the 2 vials so that the vial of alteplase is on the bottom and allow the diluent to flow down through the transfer device; about 0.5 mL of Sterile Water for Injection will remain in the diluent vial. Remove the transfer device and diluent vial from the alteplase vial and discard. Swirl gently to dissolve the powder. DO NOT SHAKE.
Slight foaming is not unusual after reconstitution; let the solution stand undisturbed for several minutes to allow large bubbles to dissipate.
Storage: Use within 8 hours of reconstitution.[29126]
 
Dilution
Alteplase may be administered as the reconstituted 1 mg/mL solution or further diluted immediately prior to administration in an equal volume of 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a concentration of 0.5 mg/mL. Polyvinyl chloride bags or glass vials are acceptable for dilution.[29126]
ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 1 mg/mL.[64020]
ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 1 mg/mL.
 
Bolus Dose Preparation
The bolus dose may be prepared in 1 of the following ways:
Remove the appropriate volume from the reconstituted (1 mg/mL) vial using a syringe and needle. If this method is used with 50-mg vials, the syringe should not be primed with air and the needle should be inserted into the vial stopper. If the 100-mg vial is used, the needle should be inserted away from the puncture mark made by the transfer device.
Remove the appropriate indication-specific 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 indication-specific volume as a bolus at the initiation of the infusion.[29126]
 
IV Infusion
50-mg vials: Administer using a polyvinyl chloride bag or glass vial and infusion set.
100-mg vials: Remove from the vial the amount of drug that is not needed for the indication-specific dose for the patient. Insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted alteplase. Hang the reconstituted vial from the clear plastic hanger attached to the vial label.
Length of infusion depends upon indication.
If extravasation occurs, terminate the infusion at that site and apply local therapy.[29126]

Central Venous Catheter Instillation Administration
Alteplase is instilled into the occluded lumen of a central venous catheter.
Consider other reasons for catheter dysfunction, such as catheter malposition, mechanical failure, constriction by a suture, and lipid deposits or drug precipitates within the lumen, before treatment with alteplase.
Avoid vigorous suction during attempts to determine catheter occlusion to prevent damage to the vascular wall or collapse of soft-walled catheters.
Avoid excessive pressure when alteplase is instilled into the catheter. Such force could cause rupture of the catheter or expulsion of the clot into the circulation.[33184]
 
Reconstitution
Aseptically withdraw 2.2 mL Sterile Water for Injection. Do not use Bacteriostatic Water for Injection.
Inject the 2.2 mL of Sterile Water for Injection into the vial, directing the diluent stream into the powder. Slight foaming is not unusual; let the vial stand undisturbed to allow large bubbles to dissipate.
Mix gently by swirling until the contents completely dissolve. Complete dissolution should occur within 3 minutes. DO NOT SHAKE. The reconstituted product results in a colorless to pale yellow clear solution containing 1 mg/mL alteplase at a pH of about 7.3.
Storage: Use immediately after reconstitution. The solution may be used for intracatheter instillation within 8 hours following reconstitution when stored at 2 to 30 degrees C (36 to 86 degrees F).
No other medication should be added to solutions containing alteplase.[33184]
 
Cryopreserved Bolus Injection Preparation
NOTE: Alteplase is not FDA-approved to be prepared as cryopreserved bolus injections.
In vitro data support that cryopreserved alteplase solutions maintain bioactivity in propylene syringes for 6 months and in glass vials for 2 weeks. Using aseptic technique, dilute alteplase to a concentration of 1 mg/mL.
For propylene syringes: Withdraw 1 mL into polypropylene syringes and cryopreserve at -20 degrees C. Aliquots retain bioactivity for 6 months.
For glass vials: Withdraw 2 mL into glass vials and cryopreserve at -70 degrees C for 2 weeks; then, thaw and maintain at 22 to 24 degrees C for 24 hours; then, store at -70 degrees C for up to 19 days.[26140]
 
Intracatheter Instillation
Withdraw 2 mL (2 mg) of solution from the reconstituted vial.
Instill the appropriate dose into the occluded catheter.
After 30 minutes of dwell time, assess catheter function by attempting to aspirate blood.
If the catheter is not functional after 30 minutes, allow the solution to remain for an additional 90 minutes (120 minutes of total dwell time) and assess catheter function by attempting to aspirate blood and catheter contents.
If catheter function is not restored after 120 minutes, a second dose may be instilled. After instillation of second dose, check catheter function 30 minutes and, if needed, 120 minutes after second instillation.
If catheter function is restored, aspirate 4 to 5 mL of blood in patients weighing 10 kg or more or 3 mL in patients weighing less than 10 kg to remove alteplase and residual clot. Gently irrigate the catheter with 0.9% Sodium Chloride Injection.
Discard any unused solution.[33184]
 
Intrapleural Catheter Administration†
Preparation
Dilute 2 to 10 mg in a sufficient amount of 0.9% Sodium Chloride Injection. Multiple concentrations have been used.
2 mg has been diluted with 20 mL of 0.9% Sodium Chloride Injection.
3 mg has been diluted with 10 to 20 mL of 0.9% Sodium Chloride Injection.
4 mg has been diluted with 10 to 50 mL of 0.9% Sodium Chloride Injection.
10 mg has been diluted with 30 mL of 0.9% Sodium Chloride Injection.
 
Intrapleural Instillation
Inject via chest tube followed by 5 mL 0.9% Sodium Chloride flush and clamp chest tube for 1 hour, then allow to drain for 1 hour.

intracranial bleeding / Delayed / 0.4-15.4
GI bleeding / Delayed / 5.0-5.0
stroke / Early / 1.2-1.6
retroperitoneal bleeding / Delayed / 0-1.0
thrombosis / Delayed / 0-1.0
bradycardia / Rapid / Incidence not known
ventricular tachycardia / Early / Incidence not known
cholesterol microembolization / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
renal failure / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
coma / Early / Incidence not known
seizures / Delayed / Incidence not known
cerebral edema / Early / Incidence not known
thromboembolism / Delayed / Incidence not known
AV block / Early / Incidence not known
cardiac tamponade / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
heart failure / Delayed / Incidence not known
pericarditis / Delayed / Incidence not known
pulmonary edema / Early / Incidence not known
pleural effusion / Delayed / Incidence not known

bleeding / Early / 10.0
premature ventricular contractions (PVCs) / Early / Incidence not known
livedo reticularis / Delayed / Incidence not known
hypertension / Early / Incidence not known
hypotension / Rapid / Incidence not known

ecchymosis / Delayed / 1.0-1.0
epistaxis / Delayed / 0-1.0
infection / Delayed / 0-1.0
vomiting / Early / Incidence not known
nausea / Early / Incidence not known
fever / Early / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known

Activase, Cathflo Activase

Rx

Parenteral tissue plasminogen activator (tPA)
Used for the treatment of acute ischemic stroke, acute myocardial infarction, and acute massive pulmonary embolism, and for the restoration of function to central venous access devices
Associated with significant, sometimes fatal, internal or external bleeding

100 mg IV over 2 hours. Start parenteral anticoagulation near the end of or immediately after the alteplase infusion when the partial thromboplastin time or thrombin time returns to twice normal or less.

0.5 mg/kg/hour IV for 6 hours is a commonly used regimen; doses of 0.01 to 3.75 mg/kg/hour for 1 to 192 hours have been reported. Heparin therapy either during or immediately following thrombolytic therapy has been recommended; the loading dose may be omitted. Increased bleeding complications have been reported in pediatric patients receiving higher doses; therefore, some authors recommend initiating therapy at the lower end of the dosage range and increasing the dose only if necessary for adequate lysis.

0.1 to 0.3 mg/kg/hour IV for 6 to 48 hours has been recommended. Regimens reported in small case series and case reports of neonates (n = 94) have included loading doses up to 0.75 mg/kg IV over 10 to 60 minutes followed by infusions of 0.02 to 1 mg/kg/hour IV for 0.5 to 264 hours. Although the overall outcome in these reports was 94% patency restoration (68% to 79% complete clot dissolution and 14% to 26% partial clot dissolution), the number of patients in each report was too small and the regimens too varied to draw definitive conclusions regarding the appropriate dose. Heparin therapy either during or immediately following thrombolytic therapy has been recommended; the loading dose may be omitted. Increased bleeding complications have been reported in pediatric patients receiving higher doses; therefore, some authors recommend initiating therapy at the lower end of the dosage range and increasing the dose only if necessary for adequate lysis.

0.6 mg/kg (Max: 50 mg) IV over 15 minutes in persons with extreme hemodynamic instability, such as cardiac arrest.

0.9 mg/kg (Max: 90 mg) IV over 60 minutes with initial 10% of the total dose given as bolus over 1 minute within 3 hours, or 4.5 hours for select patients, of stroke symptom onset or baseline well state. Guidelines recommend alteplase treatment in the 3- to 4.5-hour window for patients 80 years or younger, without a history of diabetes or prior stroke, National Institutes of Health Stroke Scale (NIHSS) score of 25 or less, not taking any oral anticoagulants, and without imaging evidence of ischemic injury involving more than one-third of the middle cerebral artery territory.

Guidelines do not recommend the use of thrombolytics for acute ischemic stroke in pediatric patients; however, 0.9 mg/kg (Max: 90 mg) IV over 60 minutes with initial 10% of the total dose given as bolus over 1 minute has been used in a small number of pediatric patients. Adult guideline recommendations were often not followed; poor neurologic outcome was common in the patients that received alteplase. In adults, alteplase is recommended to start within 3 hours, or 4.5 hours for select patients, of stroke symptom onset or baseline well state.

2 mg/2 mL instilled into the dysfunctional catheter for 2 hours. A second dose may be instilled if catheter function is not restored 2 hours after the first dose. Efficacy and safety information for doses more than 2 mg/dose or total doses more than 4 mg is not available. Dwell times of 0.5 to 4 hours have been recommended. For multiple lumens, treat 1 lumen at a time. For subcutaneous ports, a dose of 2 mg diluted in 3 mL of 0.9% Sodium Chloride Injection has been recommended. Doses of 1 to 2 mg instilled into the lumen(s) of central venous catheters or PICC lines, allowed to dwell for 15 minutes to 4 hours, then removed by aspiration, have been reported effective in establishing patency.

2 mg/2 mL instilled into the dysfunctional catheter for 2 hours. A second dose may be instilled if catheter function is not restored 2 hours after the first dose. Efficacy and safety information for doses more than 2 mg/dose or total doses more than 4 mg is not available. Dwell times of 0.5 to 4 hours have been recommended. For multiple lumens, treat 1 lumen at a time. For subcutaneous ports, a dose of 2 mg diluted in 3 mL of 0.9% Sodium Chloride Injection has been recommended.

110% of the internal lumen volume of the catheter instilled with alteplase 1 mg/mL, not to exceed 2 mg/2 mL. A second dose may be instilled if catheter function is not restored 2 hours after the first dose. Efficacy and safety information for doses more than 2 mg/dose or total doses more than 4 mg is not available. Dwell times of 0.5 to 4 hours have been recommended. For multiple lumens, treat 1 lumen at a time. For subcutaneous ports, a dose of 2 mg diluted in 3 mL of 0.9% Sodium Chloride Injection has been recommended.

110% of the internal lumen volume of the catheter instilled with alteplase 1 mg/mL, not to exceed 2 mg/2 mL. A second dose may be instilled if catheter function is not restored 2 hours after the first dose. Efficacy and safety information for doses more than 2 mg/dose or total doses more than 4 mg is not available. A solution of 0.5 to 1 mg diluted in 2 mL of 0.9% Sodium Chloride Injection sufficient to fill the occluded catheter has also been used. Dwell times of 0.5 to 4 hours have been recommended. For multiple lumens, treat 1 lumen at a time. For subcutaneous ports, 0.5 mg diluted in 3 mL of 0.9% Sodium Chloride Injection has been recommended.

Dosage not established. 10 to 30 mg intracoronary over 5 to 20 minutes followed by IV infusion has been used.[24918] [58387] [58388] 

Dosage not established. 40 to 50 mg IV over 1 hour after intracoronary dosing has been used.[24918] [58387]

15 mg IV bolus, followed by 50 mg IV over next 30 minutes, and then 35 mg IV over the next 60 minutes.[29126] [55688] The safety and efficacy of the accelerated infusion have only been studied with concomitant heparin and aspirin.[29126] Fibrinolytic therapy is recommended for ST-elevation myocardial infarction (STEMI) patients with the onset of symptoms in the previous 12 hours when the anticipated first medical contact to primary PCI time is more than 120 minutes. Fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of onset and a large area of myocardium at risk or hemodynamic instability. Additionally, fibrinolytic therapy is recommended for STEMI patients with cardiogenic shock who are not candidates for either PCI or CABG. When fibrinolytic therapy is chosen as primary reperfusion strategy, administer within 30 minutes of hospital arrival.[55688]

15 mg IV bolus, followed by 0.75 mg/kg IV over next 30 minutes, and then 0.5 mg/kg IV over the next 60 minutes.[29126] [55688] The safety and efficacy of the accelerated infusion have only been studied with concomitant heparin and aspirin. Fibrinolytic therapy is recommended for ST-elevation myocardial infarction (STEMI) patients with the onset of symptoms in the previous 12 hours when the anticipated first medical contact to primary PCI time is more than 120 minutes. Fibrinolytic therapy is reasonable for patients with STEMI if there is clinical and/or ECG evidence of ongoing ischemia within 12 to 24 hours of onset and a large area of myocardium at risk or hemodynamic instability. Additionally, fibrinolytic therapy is recommended for STEMI patients with cardiogenic shock who are not candidates for either PCI or CABG. When fibrinolytic therapy is chosen as primary reperfusion strategy, administer within 30 minutes of hospital arrival.[55688]

6 to 10 mg IV bolus, followed by 50 to 54 mg/hour IV for first hour, then 20 mg/hour IV for 2 hours.

0.075 mg/kg mg IV bolus, followed by 0.675 mg/kg/hour IV for first hour, then 0.25 mg/kg/hour IV for 2 hours.

0.01 mg/kg/hour (Max: 1 mg/hour) catheter-directed continuous intrathrombus infusion.    Guidelines recommend anticoagulant therapy alone over catheter-directed thrombolysis (CDT) in patients with acute proximal DVT; however, guidelines do state that patients who are most likely to benefit from CDT are those with iliofemoral DVT, symptoms for less than 14 days, good functional status, life expectancy of more than 1 year, and a low risk of bleeding. Use of pharmacomechanical CDT is suggested over the use of infusion-only CDT.

Various doses and administration times have been studied; the lowest effective dose has not been determined. Common doses used in combination with heparin include 0.5 to 2.5 mg/hour. Weight-based dosing of 0.05 to 0.1 mg/kg/hour for up to 12 hours (Max: 100 mg) also has been studied. In clinical trials, alteplase was administered by catheter-directed intra-arterial administration. Administration time varied but typically continued until complete lysis was achieved or for up to 12 hours. Guidelines recommend immediate systemic anticoagulation with unfractionated heparin in patients with acute limb ischemia due to arterial emboli or thrombosis and recommend reperfusion with surgery over intra-arterial thrombolysis.

1 or 2 mg alteplase instilled in each catheter lumen at the end of hemodialysis session; 2 mg after each dialysis session and 1 mg alteplase in only 1 of 3 dialysis sessions each week, with heparin instilled after the other 2 sessions has been used.

4 mg intrapleurally as a single dose or as multiple doses 24 hours apart.

10 mg intrapleurally twice daily for 3 days in combination with dornase alfa.

2 to 4 mg intrapleurally every 8 to 24 hours for 3 days. Some studies have used in combination with dornase alfa.

Available data are limited, and efficacy has not been established. Due to a lack of clinical data, the National Institutes of Health (NIH) COVID-19 treatment guidelines do not recommend for or against the use of thrombolytics, such as alteplase.[65314] 25 mg IV over 2 hours followed by 25 mg continuous IV infusion over 22 hours (Max: 0.9 mg/kg) has been used as salvage therapy.[65311] [65327] In a case series (n = 3) of critically ill patients with ARDS and respiratory failure given alteplase, an initial improvement in PaO2/FiO2 (P/F) ratio ranging from 11% to 100% was observed in all 3 patients; however, improvements were transient. Heparin was initiated or resumed immediately after the completion of alteplase infusion without bleeding complications. Redosing and/or using a higher bolus dose (50 to 100 mg) without holding anticoagulation is postulated that may provide a more durable response.[65327] Patients with a P/F ratio less than 50 and a pCO2 more than 60 despite prone positioning and maximal ventilatory support may be candidates for alteplase use, particularly if extracorporeal membrane oxygenation (ECMO) is not available. May also consider use in patients with progressive pulmonary deterioration where there is no further mechanical ventilation capacity.[65311] Additional clinical evaluation is needed.

3 mg IV or intra-arterial bolus, then 10 mg/hour continuous IV or intra-arterial infusion starting within 24 to 48 hours of the initial cold injury and continuing until specialists recommend discontinuation. Administer anticoagulation concurrently. Guidelines suggest thrombolytic therapy to salvage at-risk tissue for deep frostbite injury with potential significant morbidity.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. The risks of alteplase therapy may be increased in patients with significant hepatic impairment and should be weighed against the anticipated benefits.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abciximab: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Acetaminophen; Aspirin: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Alpha interferons: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Altretamine: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Aminocaproic Acid: (Contraindicated) The actions of aminocaproic acid can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Anagrelide: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Antithrombin III: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
Apixaban: (Contraindicated) Due to the increased bleeding risk, avoid concurrent use of apixaban with thrombolytic agents.
Aprotinin: (Contraindicated) Aprotinin interferes with fibrinolysis by inhibiting the actions of kallikrein and plasmin, and it could inhibit fibrinolysis by thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
Argatroban: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
Arsenic Trioxide: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Aspirin, ASA: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Carisoprodol: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Dipyridamole: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution. (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Omeprazole: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Aspirin, ASA; Oxycodone: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and thrombolytic agents are used concomitantly. Coadministration of betrixaban and thrombolytic agents may increase the risk of bleeding.
Bexarotene: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Bismuth Subsalicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Bivalirudin: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Chlorambucil: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Choline Salicylate; Magnesium Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Cilostazol: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Clofarabine: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Clopidogrel: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Dabigatran: (Major) Based on the pharmacology of dabigatran, other oral anticoagulants and thrombolytic agents could cause additive risk of bleeding when given concurrently with dabigatran.
Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving dalteparin in combination with other agents known to increase the risk of bleeding such thrombolytic agents. Monitor clinical and laboratory response closely during concurrent use.
Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with thrombolytic agents.
Defibrotide: (Contraindicated) Coadministration of defibrotide with fibrinolytics (thrombolytic agents) is contraindicated. The pharmacodynamic activity and risk of hemorrhage with fibrinolytics are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic fibrinolytic therapy (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the fibrinolytic have abated.
Desirudin: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with medications which impair platelet function and to promptly report any bleeding events to the practitioner.
Dipyridamole: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Duloxetine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with medications which impair platelet function and to promptly report any bleeding events to the practitioner.
Edoxaban: (Major) Coadministration of edoxaban and thrombolytic agents should be avoided due to an increased risk of bleeding during concurrent use. Occasionally, short-term coadministration may be necessary in patients transitioning to and from edoxaban. Long-term coadminstration is not recommended. Promptly evaluate any signs or symptoms of blood loss in patients on concomitant therapy.
Enoxaparin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including thrombolytic agents, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Eptifibatide: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Estramustine: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Folate analogs: (Moderate) Due to the thrombocytopenic effects of folate analogs, when used as antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytics.
Fondaparinux: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
Garlic, Allium sativum: (Moderate) Since garlic produces clinically-significant antiplatelet effects, it should be used cautiously in patients receiving thrombolytic agents. Avoid concurrent use of herbs which interact with thrombolytic agents when possible. If Garlic supplements are taken, monitor appropriate parameters to attain proper clinical endpoints.
Ginger, Zingiber officinale: (Moderate) Since ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist, use with caution during times when bleeding is a concern. This includes patients receiving thrombolytic agents, however, no clinical data are available.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and thrombolytic agents as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if coadministered with thrombolytic agents. Caution and careful monitoring of clinical and/or laboratory parameters are warranted if green tea and thrombolytics are coadministered.
Heparin: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with coagulation such as thrombolytic agents; the risk of bleeding may be increased. If coadministration with thrombolytic agents is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Intravenous Lipid Emulsions: (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Levomilnacipran: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SNRI.
Lomustine, CCNU: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Magnesium Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Methenamine; Sodium Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Methoxsalen: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs including increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking thrombolytic agents until data confirming the safety of this drug combination are available.
Milnacipran: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SNRI.
Nitroglycerin: (Major) Two separate studies have shown that concomitant administration of IV nitroglycerin can compromise the therapeutic efficacy of alteplase. In one study, reperfusion occurred in 91% of patients receiving alteplase without nitroglycerin while only 44% of patients receiving alteplase with nitroglycerin were reperfused, however this was an uncontrolled study. In another controlled study, patients who did not receive concomitant IV nitroglycerin reperfused faster, more often, and had fewer reocclusions. It appears that when combined in vitro, nitroglycerin enhances the degradation of alteplase. Nitroglycerin may enhance the hepatic clearance of alteplase since alteplase plasma concentrations are lower in patients receiving concomitant nitroglycerin.
Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
Pentosan: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
Photosensitizing agents (topical): (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Platelet Inhibitors: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Prasugrel: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Protein C Concentrate, Human: (Major) The concomitant use of protein C concentrate and alteplase, tPA may further increase the risk of bleeding from tPA. In clinical trials, several episodes of bleeding were reported. Concurrent anticoagulant medication may have been responsible for these bleeding episodes.
Prothrombin Complex Concentrate, Human: (Major) The concomitant use of protein C concentrate and alteplase, tPA may further increase the risk of bleeding from tPA. In clinical trials, several episodes of bleeding were reported. Concurrent anticoagulant medication may have been responsible for these bleeding episodes.
Rivaroxaban: (Major) Due to the increased bleeding risk, avoid concurrent use of rivaroxaban with thrombolytic agents; the safety of concomitant use has not been studied.
Salicylates: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Salsalate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Selective serotonin reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
Thrombin Inhibitors: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
Ticagrelor: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Ticlopidine: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Tirofiban: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Tranexamic Acid: (Contraindicated) Antifibrinolytic agents, including tranexamic acid, can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with trazodone.
Tretinoin, ATRA: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Venlafaxine: (Moderate) Platelet aggregation may be impaired by venlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered concurrently with venlafaxine.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with thrombolytic agents is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease clotting like thrombolytic agents could decrease the efficacy of verteporfin therapy.
Vilazodone: (Moderate) Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with vilazodone.
Vorapaxar: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Vorinostat: (Moderate) Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytic agents.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with vortioxetine and instructed to promptly report any bleeding events to the practitioner.
Warfarin: (Contraindicated) Based on the pharmacology of warfarin, other thrombolytic agents could cause additive risk of bleeding when given concurrently with warfarin. Pre-treatment with oral anticoagulants is reported to be an independent risk factor for intracranial hemorrhage in thrombolytic-treated patients. Prothrombin times stabilized during administration of both agents will change slightly when heparin is discontinued.

Activase/Cathflo Activase Intravenous Inj Pwd F/Sol: 2.2mg, 50mg, 100mg

The maximum dosage is dependent on indication for therapy.

The maximum dosage is dependent on indication for therapy.

Safety and efficacy have not been established for systemic thrombolysis; various regimens have been used. For occluded catheters, instill no more than 4 mg/catheter.

Safety and efficacy have not been established for systemic thrombolysis; various regimens have been used. For occluded catheters, instill no more than 4 mg/catheter.

Safety and efficacy have not been established for systemic thrombolysis; various regimens have been used. For occluded catheters, instill no more than 4 mg/catheter.

Safety and efficacy have not been established for systemic thrombolysis; various regimens have been used. For occluded catheters, instill no more than 4 mg/catheter.

Alteplase exerts its action on the endogenous fibrinolytic system to convert plasminogen to plasmin by directly hydrolyzing the arginine-valine bond in plasminogen. Plasmin degrades fibrin and fibrinogen as well as the procoagulant factors V and VIII. Unlike streptokinase or urokinase, most of the activity of alteplase is dependent on the presence of fibrin. Minimal amounts of plasminogen are converted to plasmin in the absence of fibrin. Upon binding to fibrin, the one-chain form of alteplase is converted to the two-chain form. Both forms have similar fibrinolytic and plasminogen-activating potential; however, the one-chain alteplase is considerably less active in the absence of fibrin. Alteplase that is bound to fibrin acquires a high affinity for plasminogen, which is responsible for an increased activity at the fibrin surface compared to the circulation.

Alteplase is administered by IV infusion. The distribution of this agent has not been described; the initial volume of distribution approximates plasma volume. It is unknown whether alteplase crosses the placenta or is excreted into breast milk. Hepatic clearance is the predominant route of metabolism. More than 50% of the drug is cleared following discontinuation of IV infusion and 80% is cleared within 10 minutes. Limited studies in patients with myocardial infarction and patients with thromboembolic disease indicate that the terminal half-life of alteplase is approximately 45 and 30 minutes, respectively. Alteplase has been shown to be primarily excreted in the urine (80%).

There are no data on the presence of alteplase in human milk, the effects on the breast-feeding infant, or the effects on milk production. However, based on the drug's large molecular weight and short half-life, experts state that clinically significant amounts of drug are not expected to be found in breast milk.