Activase

Name: Activase

What should I avoid after receiving Activase (alteplase)?

Ask your doctor before taking aspirin or ibuprofen (Motrin, Advil) shortly after you have received alteplase. These medications can increase your risk of bleeding.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

What other drugs will affect Activase (alteplase)?

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • any medication used to prevent blood clots;

  • a blood thinner (heparin, warfarin, Coumadin, Jantoven); or

  • NSAIDs (nonsteroidal anti-inflammatory drugs)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with alteplase, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Commonly used brand name(s)

In the U.S.

  • Activase
  • Cathflo Activase

Available Dosage Forms:

  • Powder for Solution

Therapeutic Class: Thrombolytic

Pharmacologic Class: Tissue Plasminogen Activator

Precautions While Using Activase

Alteplase can cause bleeding that usually is not serious. However, serious bleeding may occur in some people. To help prevent serious bleeding, carefully follow any instructions given by your doctor. Move around as little as possible, and do not get out of bed on your own, unless your doctor tells you it is all right to do so.

Watch for any bleeding or oozing on your skin, such as around the place of injection or where blood was drawn from your arm. Also, check for blood in your urine or bowel movements. If you have any bleeding or injuries, tell your doctor or nurse right away.

What do I need to tell my doctor BEFORE I take Activase?

  • If you have an allergy to alteplase or any other part of Activase (alteplase (injection)).
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Aneurysm, arteriovenous malformations, bleeding problems, brain tumor, injury to the brain or spine in the last 3 months, seizure when stroke began, stroke, surgery on the brain or spine in the last 3 months, or high blood pressure.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Activase with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Change in color of skin to a bluish color like on the lips, nail beds, fingers, or toes.
  • Change in skin color to black or purple.
  • Chest pain or pressure.
  • Very bad dizziness or passing out.
  • Very bad headache.
  • Very bad muscle pain.

What are some other side effects of Activase?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if you have any side effects that bother you or do not go away.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Use in specific populations

Pregnancy

Pregnancy Category C

Activase is embryocidal in rabbits when intravenously administered in doses of approximately two times (3 mg/kg) the human dose for AMI. No maternal or fetal toxicity was evident at 0.65 times (1 mg/kg) the human dose in pregnant rats and rabbits dosed during the period of organogenesis. There are no adequate and well-controlled studies in pregnant women.

Nursing Mothers

It is not known whether Activase is excreted in human milk. Many drugs are excreted in human milk.

Pediatric Use

Safety and effectiveness of Activase in pediatric patients have not been established.

Geriatric Use

Acute Ischemic Stroke

In exploratory, multivariate analyses of Studies 1 and 2, age greater than 77 years was one of several interrelated baseline characteristics associated with an increased risk of intracranial hemorrhage. Efficacy results suggest a reduced but still favorable clinical outcome for Activase-treated elderly [see Clinical Studies (14.1)].

Acute Myocardial Infarction

In a large trial of accelerated-infusion Activase that enrolled 41,021 patients with AMI to one of four thrombolytic regimens [see Clinical Studies (14.2)], patients over 75 years of age, a predefined subgroup, comprised 12% of enrollment. In these patients, the incidence of stroke was 4.0% for the Activase accelerated infusion group, 2.8% for streptokinase IV [SK (IV)], and 3.2% for streptokinase SQ [SK (SQ)]. The incidence of combined 30-day mortality or nonfatal stroke was 20.6% for accelerated infusion of Activase, 21.5% for SK (IV), and 22.0% for SK (SQ).

Activase - Clinical Pharmacology

Mechanism of Action

Alteplase is a serine protease responsible for fibrin-enhanced conversion of plasminogen to plasmin. It produces limited conversion of plasminogen in the absence of fibrin.

When introduced into the systemic circulation at pharmacologic concentration, alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis.

Pharmacodynamics

Following administration of 100 mg Activase, there is a decrease (16%-36%) in circulating fibrinogen. In a controlled trial, 8 of 73 patients (11%) receiving Activase (1.25 mg/kg body weight over 3 hours) experienced a decrease in fibrinogen to below 100 mg/dL.

Pharmacokinetics

Alteplase in acute myocardial infarction (AMI) patients is rapidly cleared from the plasma with an initial half-life of less than 5 minutes. There is no difference in the dominant initial plasma half-life between the 3-hour and accelerated regimens for AMI. The plasma clearance of alteplase is 380-570 mL/min, primarily mediated by the liver. The initial volume of distribution approximates plasma volume.

How Supplied/Storage and Handling

How Supplied

Activase is supplied as a sterile, lyophilized powder in 50 mg vials containing vacuum and in 100 mg vials without vacuum.

Each 50 mg Activase vial (29 million IU) is packaged with diluent for reconstitution (50 mL Sterile Water for Injection, USP): NDC 50242-044-13.

Each 100 mg Activase vial (58 million IU) is packaged with diluent for reconstitution (100 mL Sterile Water for Injection, USP), and one transfer device: NDC 50242-085-27.

Stability and Storage

Store lyophilized Activase at controlled room temperature not to exceed 30°C (86°F), or under refrigeration (2-8°C/36-46°F). Protect the lyophilized material during extended storage from excessive exposure to light. If stored between 2-30°C (36-86°F), Activase may be used within 8 hours following reconstitution. Discard any unused solution after administration is complete.

Do not use beyond the expiration date stamped on the vial.

Activase Overview

Activase is a prescription medication used to break up or dissolve blood clots.

Activase belongs to a group of drugs called thrombolytics. These dissolve blood clots quickly to help restart blood flow to the heart and helps prevent damage to the heart muscle.

This medication is available in an injectable form to be given directly into a vein by a healthcare professional.

A common side effect of Activase is bleeding.

Activase Precautions

Serious side effects have been reported with Activase including the following:

  • Bleeding. Tell your healthcare provider right away if you have some or all of the following symptoms of bleeding.
    • bruising
    • bloody or black, tarry stools
    • bloody vomit
    • vomiting blood or brown material that resembles coffee grounds

Do not take Activase if you:

  • are allergic to Activase or any of its ingredients
  • have an active bleed
  • have a history of a brain injury
  • have had recent major surgery or trauma especially in the head
  • serevely uncontrolled high blood pressure
  • have or have had any problems managing bleeding conditions in the past

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.

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