Activase

Name: Activase

How is Activase (alteplase)given?

Alteplase is injected into a vein through an IV. A healthcare provider will give you this injection.

Alteplase is usually given within 3 hours after the first signs of stroke or heart attack symptoms. Your breathing, blood pressure, oxygen levels, and other vital signs will be watched closely.

You will also be watched closely for several hours after receiving alteplase, to make sure you do not have an allergic reaction to the medication.

When used to clear blood clots from a catheter, alteplase is given in 1 or 2 doses. After the first dose, a small amount of blood is withdrawn through the catheter to make sure it is cleared of blood clots. If blood cannot be easily withdrawn 2 hours after the first dose of alteplase, a second dose may be given.

After treatment with alteplase, your doctor may prescribe a blood thinner or other medication to help prevent future blood clots. Carefully follow all dosing instructions. These medications can make it easier for you to bleed, even from a minor injury.

Before Using Activase

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Heart attack, stroke, pulmonary embolism—Appropriate studies have not been performed on the relationship of age to the effects of alteplase injection in the pediatric population. Safety and efficacy have not been established.

Central venous access devices—Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of alteplase injection in children.

Geriatric

Heart attack, stroke, pulmonary embolism—No information is available on the relationship of age to the effects of alteplase in geriatric patients.

Central venous access devices—Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of alteplase in the elderly.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Defibrotide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Abciximab
  • Acenocoumarol
  • Alteplase, Recombinant
  • Anistreplase
  • Apixaban
  • Ardeparin
  • Argatroban
  • Aspirin
  • Bemiparin
  • Benazepril
  • Bivalirudin
  • Captopril
  • Certoparin
  • Cilostazol
  • Clopidogrel
  • Dabigatran Etexilate
  • Dalteparin
  • Danaparoid
  • Desirudin
  • Dipyridamole
  • Edoxaban
  • Enalapril
  • Enalaprilat
  • Enoxaparin
  • Eptifibatide
  • Fondaparinux
  • Fosinopril
  • Heparin
  • Lepirudin
  • Lisinopril
  • Moexipril
  • Nadroparin
  • Nitroglycerin
  • Parnaparin
  • Pentosan Polysulfate Sodium
  • Perindopril
  • Phenindione
  • Phenprocoumon
  • Prasugrel
  • Protein C
  • Quinapril
  • Ramipril
  • Reteplase, Recombinant
  • Reviparin
  • Rivaroxaban
  • Streptokinase
  • Sulfinpyrazone
  • Tenecteplase
  • Ticlopidine
  • Tinzaparin
  • Tirofiban
  • Trandolapril
  • Treprostinil
  • Urokinase
  • Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Bleeding problems or a history of bleeding in any part of the body or
  • Blood vessel problems (eg, aneurysm or arteriovenous malformation) or
  • Brain disease or tumor or
  • Hypertension (high blood pressure), uncontrolled or
  • Stroke, history of or
  • Surgery or injury to the brain or spine, recent (within three months)—This medicine should not be used in these conditions.
  • Blood clots, history of or
  • Diabetic eye problems (eg, hemorrhagic retinopathy) or
  • Heart infections (eg, pericarditis or endocarditis) or
  • Injections into a blood vessel or
  • Kidney disease, severe or
  • Liver disease, severe or
  • Placement of any catheter (tube) into the body or
  • Surgery or injury of any kind, major and recent—The chance of serious bleeding may be increased.
  • Catheter infection or
  • Deep venous thrombosis (blood clots in the legs) or
  • High cholesterol, history of—The chance of having a serious side effect may be increased.
  • Heart rhythm problems—Use with caution. May make this condition worse.

What are some things I need to know or do while I take Activase?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Very bad and sometimes deadly bleeding problems have happened with Activase. Talk with the doctor.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • Use care to prevent injury and avoid falls or crashes.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • If you are 75 or older, use this medicine with care. You could have more side effects.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Activase while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

How is this medicine (Activase) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as a shot into a vein.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

How do I store and/or throw out Activase?

  • If you need to store Activase at home, talk with your doctor, nurse, or pharmacist about how to store it.

Warnings and Precautions

Bleeding

Activase can cause significant, sometimes fatal, internal or external bleeding, especially at arterial and venous puncture sites. Avoid intramuscular injections and trauma to the patient while on Activase. Perform venipunctures carefully and only as required. To minimize bleeding from noncompressible sites, avoid internal jugular and subclavian venous punctures. If an arterial puncture is necessary during Activase infusion, use an upper extremity vessel that is accessible to manual compression, apply pressure for at least 30 minutes, and monitor the puncture site closely.

Because of the higher risk of intracranial hemorrhage in patients treated for acute ischemic stroke, limit treatment to facilities that can provide timely access to appropriate evaluation and management of intracranial hemorrhage.

Fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported.

Aspirin and heparin have been administered concomitantly with and following infusions of Activase in the management of acute myocardial infarction and pulmonary embolism, but the concomitant administration of heparin and aspirin with and following infusions of Activase for the treatment of acute ischemic stroke during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or Activase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of Activase, while patients are still receiving anticoagulant therapy.

If serious bleeding occurs, terminate the Activase infusion.

In the following conditions, the risks of bleeding with Activase therapy for all approved indications are increased and should be weighed against the anticipated benefits:

  • Recent major surgery or procedure, (e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels)
  • Cerebrovascular disease
  • 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
  • Septic thrombophlebitis or occluded AV cannula at seriously infected site
  • Advanced age [see Use in Specific Populations (8.5)]
  • Patients currently receiving anticoagulants (e.g., warfarin sodium)
  • Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

Orolingual Angioedema

Orolingual angioedema has been observed during and up to 2 hours after Activase infusion in patients treated for acute ischemic stroke and acute myocardial infarction [see Adverse Reactions (6.1)]. In many cases, patients received concomitant angiotensin-converting enzyme inhibitors [see Drug Interactions (7)]. Monitor patients treated with Activase during and for several hours after infusion for orolingual angioedema. If angioedema develops, discontinue the Activase infusion and promptly institute appropriate therapy (e.g., antihistamines, intravenous corticosteroids, epinephrine).

Cholesterol Embolization

Cholesterol embolism has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. Cholesterol embolism may present with livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, or rhabdomyolysis and can be fatal. It is associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.

Reembolization of Deep Venous Thrombi during Treatment for Acute Massive Pulmonary Embolism

Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE. Consider the possible risk of reembolization due to the lysis of underlying deep venous thrombi in this setting.

Coagulation Tests May Be Unreliable during Activase Therapy

Coagulation tests and measures of fibrinolytic activity may be unreliable during Activase therapy, unless specific precautions are taken to prevent in vitro artifacts. When present in blood at pharmacologic concentrations, Activase remains active under in vitro conditions, which can result in degradation of fibrinogen in blood samples removed for analysis.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential or the effect on fertility. Short-term studies, which evaluated tumorigenicity of Activase and effect on tumor metastases in rodents, were negative.

Studies to determine mutagenicity (Ames test) and chromosomal aberration assays in human lymphocytes were negative at all concentrations tested. Cytotoxicity, as reflected by a decrease in mitotic index, was evidenced only after prolonged exposure and only at the highest concentrations tested.

Patient Counseling Information

Following Activase administration, patients are at increased risk of bleeding internally or externally. Advise patients to contact a health-care professional if they experience symptoms or signs consistent with bleeding (e.g., unusual bruising, pink or brown urine, red or black or tarry stools, coughing up blood, vomiting blood or blood that looks like coffee grounds), headache, or stroke symptoms.

Activase® (Alteplase)
Manufactured by:
Genentech, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA
94080-4990

Activase® is a registered trademark of Genentech, Inc.
©2017 Genentech, Inc.

Representative sample of labeling (see the HOW SUPPLIED section for complete listing):

PRINCIPAL DISPLAY PANEL - Kit Carton - 50 mg

NDC 50242-044-13

ALTEPLASE
Activase®

for intravenous use

50 mg (29 million IU)

a tissue plasminogen activator

10136622

Genentech

PRINCIPAL DISPLAY PANEL - Kit Carton - 100 mg

NDC 50242-085-27

ALTEPLASE
Activase®

for intravenous use

100 mg (58 million IU)

a tissue plasminogen activator

10136646

Genentech

Activase 
alteplase kit
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-044
Packaging
# Item Code Package Description
1 NDC:50242-044-13 1 KIT in 1 CARTON
Quantity of Parts
Part # Package Quantity Total Product Quantity
Part 1 1 VIAL, SINGLE-USE 50 mL
Part 2 1 VIAL, SINGLE-USE 50 mL
Part 1 of 2
Activase 
alteplase injection, powder, lyophilized, for solution
Product Information
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ALTEPLASE (ALTEPLASE) ALTEPLASE 50 mg  in 50 mL
Inactive Ingredients
Ingredient Name Strength
ARGININE 1.7 g  in 50 mL
PHOSPHORIC ACID 0.5 g  in 50 mL
POLYSORBATE 80 4 mg  in 50 mL
Packaging
# Item Code Package Description
1 50 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA103172 11/13/1987
Part 2 of 2
STERILE WATER 
water injection
Product Information
Route of Administration INTRAVENOUS DEA Schedule     
Inactive Ingredients
Ingredient Name Strength
Water 50 mL  in 50 mL
Packaging
# Item Code Package Description
1 50 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA103172 11/13/1987
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA103172 11/13/1987
Activase 
alteplase kit
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50242-085
Packaging
# Item Code Package Description
1 NDC:50242-085-27 1 KIT in 1 CARTON
Quantity of Parts
Part # Package Quantity Total Product Quantity
Part 1 1 VIAL, SINGLE-USE 100 mL
Part 2 1 VIAL, SINGLE-USE 100 mL
Part 1 of 2
Activase 
alteplase injection, powder, lyophilized, for solution
Product Information
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ALTEPLASE (ALTEPLASE) ALTEPLASE 100 mg  in 100 mL
Inactive Ingredients
Ingredient Name Strength
ARGININE 3.5 g  in 100 mL
PHOSPHORIC ACID 1 g  in 100 mL
POLYSORBATE 80 11 mg  in 100 mL
Packaging
# Item Code Package Description
1 100 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA103172 11/13/1987
Part 2 of 2
STERILE WATER 
water injection
Product Information
Route of Administration INTRAVENOUS DEA Schedule     
Inactive Ingredients
Ingredient Name Strength
Water 100 mL  in 100 mL
Packaging
# Item Code Package Description
1 100 mL in 1 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA103172 11/13/1987
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA103172 11/13/1987
Labeler - Genentech, Inc. (080129000)
Registrant - Genentech, Inc. (080129000)
Establishment
Name Address ID/FEI Operations
Genentech, Inc. (SSF) 080129000 ANALYSIS(50242-044, 50242-085), MANUFACTURE(50242-044, 50242-085)
Establishment
Name Address ID/FEI Operations
Genentech, Inc. (Vacaville) 004074162 ANALYSIS(50242-044, 50242-085)
Establishment
Name Address ID/FEI Operations
Genentech, Inc. (Hillsboro) 833220176 ANALYSIS(50242-044, 50242-085), PACK(50242-044, 50242-085)
Revised: 01/2017   Genentech, Inc.

Description

Activase is a tissue plasminogen activator produced by recombinant DNA technology. It is a sterile, purified glycoprotein of 527 amino acids. It is synthesized using the complementary DNA (cDNA) for natural human tissue-type plasminogen activator obtained from a human melanoma cell line. Activase is a sterile, white to off-white, lyophilized powder for intravenous administration after reconstitution with Sterile Water for Injection, USP.

Table 6: Quantitative Composition of the Lyophilized Product

  100 mg Vial 50 mg Vial
Alteplase 100 mg (58 million IU) 50 mg (29 million IU)
L-Arginine 3.5 g 1.7 g
Phosphoric Acid 1 g 0.5 g
Polysorbate 80 10 mg 5 mg
Vacuum No Yes

Biological potency is determined by an in vitro clot lysis assay and is expressed in International Units (IU).

The reconstituted preparation results in a colorless to pale yellow transparent solution containing Activase 1 mg/mL at approximately pH 7.3. The osmolality of this solution is approximately 215 mOsm/kg.

Manufacturer

  • Genentech, Inc.

Activase Drug Class

Activase is part of the drug class:

  • Antithrombotic Enzymes

Inform MD

Before taking Activase, tell your doctor about all of your medical conditions. Especially tell your doctor is you:

  • are allergic to Activase or any of its ingredients
  • are over 75 years old
  • are pregnant or breastfeeding
  • are taking oral anticoagulants (blood thinners), see the “Alteplase Drug Interactions” section.
  • have had recent major surgery or trauma
  • have had a previous stroke or heart attack
  • have had black, tarry stools or blood in the urine recently
  • have hypertension (high blood pressure): systolic BP ≥175 mm Hg and/or diastolic BP ≥110 mm Hg
  • have had a recent infection
  • have heart problems
  • have eye problems 
  • have kidney problems
  • have liver problems
  • have or have had any problems managing bleeding conditions in the past

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Activase Dosage

Alteplase is injected into a vein through an IV. A healthcare provider will give you this injection.

Alteplase is usually given within 3 hours after the first signs of stroke or heart attack symptoms. Your breathing, blood pressure, oxygen levels, and other vital signs will be watched closely.

You will also be watched closely for several hours after receiving alteplase, to make sure you do not have an allergic reaction to the medication.

When used to clear blood clots from a catheter, alteplase is given in 1 or 2 doses. After the first dose, a small amount of blood is withdrawn through the catheter to make sure it is cleared of blood clots. If blood cannot be easily withdrawn 2 hours after the first dose of alteplase, a second dose may be given.

After treatment with alteplase, your doctor may prescribe a blood thinner or other medication to help prevent future blood clots. Carefully follow all dosing instructions. These medications can make it easier for you to bleed, even from a minor injury.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Because you will receive alteplase in a clinical setting, you are not likely to miss a dose.

Alteplase Breastfeeding Warnings

There are no data on the excretion of alteplase into human milk. The manufacturer recommends that caution be used when administering alteplase to nursing women.

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