Activase

Name: Activase

Do I need a prescription for alteplase (TPA, Activase, Cathflo Activase)?

Yes

Which drugs or supplements interact with alteplase (TPA, Activase, Cathflo Activase)?

Alteplase breaks down clots and thereby interferes with the body's ability to stop bleeding. Therefore, drugs which also interfere with the body's ability to form blood clots (or the clot-promoting effects of platelets) increase the risk of bleeding in patients receiving alteplase. Such drugs include

  • warfarin (Coumadin, Jantoven),
  • aspirin, and
  • nonsteroidal anti-inflammatory drugs (NSAIDs), for example,
    • ibuprofen (Motrin, Advil),
    • naproxen (Naprosyn, Aleve),
    • nabumetone (Relafen), and
    • platelet inhibitors such as clopidogrel (Plavix), prasugrel (Effeint), cangrelor (Kengreal), ticagrelor (Brilinta).

Is alteplase (TPA, Activase, Cathflo Activase) safe to use during pregnancy or while breastfeeding?

  • Alteplase has been shown to cause damage to embryos of rabbits. No damage has been reported in humans. Doctors must carefully balance potential risks and possible benefits when prescribing alteplase to pregnant women.
  • It is not known whether alteplase passes into breast milk.

What is Activase (alteplase)?

Alteplase is a thrombolytic (THROM-bo-LIT-ik) drug, sometimes called a "clot-busting" drug. It helps your body produce a substance that dissolves unwanted blood clots.

Alteplase is used to treat a stroke caused by a blood clot or other obstruction in a blood vessel. Alteplase is also used to prevent death from a heart attack (acute myocardial infarction).

Alteplase is also used to treat a blood clot in the lung (pulmonary embolism).

Alteplase is also used to dissolve blood clots that have formed in or around a catheter placed inside a blood vessel. This improve the flow of medicines injected in through the catheter, or blood drawn out through the catheter.

Alteplase may also be used for purposes not listed in this medication guide.

Activase Side Effects

Along with its needed effects, a medicine 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:

More common
  • 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
Rare
  • 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
Incidence not known
  • 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

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Uses of Activase

  • It is used to treat blood clots.
  • It is used to treat a heart attack.
  • It is used to prevent strokes.
  • It may be given to you for other reasons. Talk with the doctor.

Drug Interactions

The interaction of Activase with other cardioactive or cerebroactive drugs has not been studied. Anticoagulants and antiplatelet drugs increase the risk of bleeding if administered prior to, during, or after Activase therapy.

In the post-marketing setting, there have been reports of orolingual angioedema in patients (primarily patients with AIS) receiving concomitant angiotensin-converting enzyme inhibitors. [see Warnings and Precautions (5.2)].

Indications

Acute Ischemic Stroke

Activase is indicated for the treatment of acute ischemic stroke.

Exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment [see CONTRAINDICATIONS]. Initiate treatment as soon as possible but within 3 hours after symptom onset.

Acute Myocardial Infarction

Activase is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure.

Limitation Of Use

The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose AMI puts them at low risk for death or heart failure.

Pulmonary Embolism

Activase is indicated for the lysis of acute massive pulmonary embolism, defined as:

  • Acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments.
  • Acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.

Activase Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Activase, there are no specific foods that you must exclude from your diet when recieving this medication.

Side effects

The following adverse reactions are discussed in greater detail in the other sections of the label:

  • Bleeding [see CONTRAINDICATIONS , WARNINGS AND PRECAUTIONS]
  • Orolingual Angioedema [see WARNINGS AND PRECAUTIONS]
  • Cholesterol Embolization [see WARNINGS AND PRECAUTIONS]
  • Reembolization of Deep Venous Thrombi during Treatment for Acute Massive Pulmonary Embolism [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The most frequent adverse reaction associated with Activase in all approved indications is bleeding.

Bleeding

Acute Ischemic Stroke (AIS)

In clinical studies in patients with AIS (Studies 1 and 2) the incidence of intracranial hemorrhage, especially symptomatic intracranial hemorrhage, was higher in Activase-treated patients than in placebo patients. A dose-finding study of Activase suggested that doses greater than 0.9 mg/kg may be associated with an increased incidence of intracranial hemorrhage.

The incidence of all-cause 90-day mortality, intracranial hemorrhage, and new ischemic stroke following Activase treatment compared to placebo are presented in Table 3 as a combined safety analysis (n=624) for Studies 1 and 2. These data indicate a significant increase in intracranial hemorrhage following Activase treatment, particularly symptomatic intracranial hemorrhage within 36 hours. There was no increase in the incidences of 90-day mortality or severe disability in Activase-treated patients compared to placebo.

Table 3: Combined Safety Outcomes for Studies 1 and 2

  Placebo
(n= 312)
Activase
(n=312)
p-Valueb
All-Cause 90-day Mortality 64 (20.5%) 54 (17.3%) 0.36
Total ICHa 20 (6.4%) 48 (15.4%) <0.01
Symptomatic 4 (1.3%) 25 (8.0%) <0.01
Asymptomatic 16 (5.1%) 23 (7.4%) 0.32
Symptomatic Intracranial Hemorrhage within 36 hours 2 (0.6%) 20 (6.4%) <0.01
New Ischemic Stroke (3-months) 17 (5.4%) 18 (5.8%) 1.00
a Within trial follow-up period. Symptomatic intracranial hemorrhage was defined as the occurrence of sudden clinical worsening followed by subsequent verification of intracranial hemorrhage on CT scan. Asymptomatic intracranial hemorrhage was defined as intracranial hemorrhage detected on a routine repeat CT scan without preceding clinical worsening.
b Fisher’s Exact Test.

Bleeding events other than intracranial hemorrhage were noted in the studies of AIS and were consistent with the general safety profile of Activase. In Studies 1 and 2, the frequency of bleeding requiring red blood cell transfusions was 6.4% for Activase-treated patients compared to 3.8% for placebo (p=0.19).

Although exploratory analyses of Studies 1 and 2 suggest that severe neurological deficit (National Institutes of Health Stroke Scale [NIHSS > 22]) at presentation was associated with an increased risk of intracranial hemorrhage, efficacy results suggest a reduced but still favorable clinical outcome for these patients.

Acute Myocardial Infarction (AMI)

For the 3-hour infusion regimen in the treatment of AMI, the incidence of significant internal bleeding (estimated as > 250 mL blood loss) has been reported in studies in over 800 patients (Table 4). These data do not include patients treated with the Activase accelerated infusion.

Table 4: Incidence of Bleeding in 3-Hour Infusion in AMI Patients

  Total Dose ≤100 mg
Gastrointestinal 5%
Genitourinary 4%
Ecchymosis 1%
Retroperitoneal <1%
Epistaxis <1%
Gingival <1%

The incidence of intracranial hemorrhage in AMI patients treated with Activase is presented in Table 5.

Table 5: Incidence of Intracranial Hemorrhage in AMI Patients

Dose Number of Patients Intracranial Hemorrhage (%)
100 mg, 3-hour 3272 0.4
≤ 100 mg, accelerated 10,396 0.7
150 mg 1779 1.3
1-1.4 mg/kg 237 0.4

A dose of 150 mg or greater should not be used in the treatment of AMI because it has been associated with an increase in intracranial bleeding.

Pulmonary Embolism (PE)

For acute massive pulmonary embolism, bleeding events were consistent with the general safety profile observed with Activase treatment of AMI patients receiving the 3-hour infusion regimen.

Allergic Reactions

Allergic-type reactions, e.g., anaphylactoid reaction, laryngeal edema, orolingual angioedema, rash, and urticaria have been reported. When such reactions occur, they usually respond to conventional therapy.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Activase. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions are frequent sequelae of the underlying disease, and the effect of Activase on the incidence of these events is unknown.

Acute Ischemic Stroke

Cerebral edema, cerebral herniation, seizure, new ischemic stroke. These events may be life threatening and may lead to death.

Acute Myocardial Infarction

Arrhythmias, AV block, cardiogenic shock, heart failure, cardiac arrest, recurrent ischemia, myocardial reinfarction, myocardial rupture, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, thromboembolism, pulmonary edema. These events may be life threatening and may lead to death. Nausea and/or vomiting, hypotension and fever have also been reported.

Pulmonary Embolism

Pulmonary reembolization, pulmonary edema, pleural effusion, thromboembolism, hypotension. These events may be life threatening and may lead to death. Fever has also been reported.

Read the entire FDA prescribing information for Activase (Alteplase)

Read More »

Activase Interactions

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.

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.

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