Activase

You should not be treated with alteplase if you are allergic to it, or if you have:

• bleeding inside your brain;

• active bleeding inside your body;

• a recent history of medical trauma or injury;

• stomach bleeding;

• a bleeding or blood clotting disorder such as hemophilia;

• severe or uncontrolled high blood pressure;

• a brain tumor or aneurysm (dilated blood vessel);

• recent major surgery;

• a recent history of head injury or surgery on your brain or spinal cord within the past 3 months; or

• a recent history of stroke (unless you are being treated for stroke).

If possible before you receive alteplase, tell your doctor if you have:

• a past history of strokes;

• a recent history of bleeding in your brain, stomach, intestines, or urinary tract;

• high blood pressure;

• heart problems;

• an infection of the lining of your heart (also called bacterial endocarditis);

• liver or kidney disease;

• eye problems caused by diabetes;

• severe bruising or infection around a vein where an IV was placed;

• if you are pregnant or have recently had a baby;

• if you have recently had an organ biopsy; or

• if you have recently had a serious injury or major surgery.

In an emergency situation it may not be possible to tell your caregivers if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medicine.

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

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Activase or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Activase. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Acute Ischemic Stroke

Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit [see Warnings and Precautions (5.1)]:

• 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 (e.g., some neoplasms, arteriovenous malformations, or aneurysms)
• Bleeding diathesis
• Current severe uncontrolled hypertension.

Acute Myocardial Infarction or Pulmonary Embolism

Do not administer Activase for treatment of AMI or PE in the following situations in which the risk of bleeding is greater than the potential benefit [see Warnings and Precautions (5.1)]:

• 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 (e.g. some neoplasms, arteriovenous malformations, or aneurysms)
• Bleeding diathesis
• Current severe uncontrolled hypertension.

Dosage Forms And Strengths

• 50 mg lyophilized powder per single use vial with 50 mL SWFI USP for reconstitution
• 100 mg lyophilized powder per single use vial with 100 mL SWFI USP for reconstitution

Storage And Handling

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.

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.

Manufactured by: Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990. Revised: Jan 2017

Included as part of the PRECAUTIONS section.

No Information Provided

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.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Activase crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Activase.

Dosage Forms & 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

Dosage Forms & 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

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Alteplase increases your risk of bleeding, which can be severe or life-threatening. Call your doctor or seek emergency medical attention if you have bleeding that will not stop. Bleeding may occur from a surgical incision, or from the skin where a needle was inserted during a blood test or while receiving injectable medication. You may also have bleeding on the inside of your body, such as in your stomach or intestines, kidneys or bladder, brain, or within the muscles.

Call your doctor at once if you have signs of bleeding inside your body, such as:

• easy bruising or bleeding (nosebleeds, bleeding gums, bleeding from a wound, incision, catheter, or needle injection);
• bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;
• red or pink urine; or
• sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance.

Also call your doctor at once if you have:

• chest pain or heavy feeling, pain spreading to the jaw or shoulder, nausea, sweating, general ill feeling;
• swelling, rapid weight gain, little or no urinating;
• severe stomach pain, nausea, and vomiting;
• darkening or purple discoloration of your fingers or toes;
• very slow heartbeats, shortness of breath, feeling light-headed;
• sudden severe back pain, muscle weakness, numbness or loss of feeling in your arms or legs;
• dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, nosebleed, anxiety, confusion, severe chest pain, shortness of breath, irregular heartbeats; or
• pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to alteplase: intravenous powder for solution

Along with its needed effects, alteplase (the active ingredient contained in Activase) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking alteplase:

• Bleeding from puncture sites and wounds
• bleeding gums
• coughing up blood
• difficulty with breathing or swallowing
• dizziness
• headache
• increased menstrual flow or vaginal bleeding
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red or black, tarry stools
• red or dark brown urine

• Chills
• confusion
• fainting
• fast heartbeat
• fever
• lightheadedness
• pain in the chest, groin, or legs, especially the calves
• pain, redness, or swelling in the arm or leg
• rapid, shallow breathing
• severe, sudden headache
• slurred speech
• sudden loss of coordination
• sudden, severe weakness or numbness in the arm or leg
• sudden, unexplained shortness of breath
• vision changes

• Anxiety
• blue lips and fingernails
• blue or pale skin
• blurred vision
• chest pain or discomfort
• chest pain, possibly moving to the left arm, neck, or shoulder
• convulsions
• cool, sweaty skin
• cough
• coughing that sometimes produces a pink frothy sputum
• decreased urine output
• dilated neck veins
• extreme fatigue
• hives or welts, itching, or skin rash
• hoarseness
• increased sweating
• large, hive-like swelling on the mouth, lips, or tongue
• loss of bladder control
• muscle spasm or jerking of all extremities
• nausea or vomiting
• pain or discomfort in the arms, jaw, back, or neck
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness of the skin
• slow or irregular breathing or heartbeat
• sudden loss of consciousness
• sweating
• swelling of the face, fingers, feet, lower legs, or ankles
• unconsciousness
• unusual tiredness or weakness
• weight gain

Alteplase has been assigned to pregnancy category C by the FDA. Alteplase has been shown to be embryocidal in rabbits at intravenous doses two times the human dose for AMI. There are no controlled data in human pregnancy. Alteplase is only recommended for use during pregnancy when benefit outweighs risk.