Alteplase

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

• anticoagulant (blood thinner) medications such as warfarin (Coumadin, Jantoven), heparin, enoxaparin (Lovenox), fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis)
• aspirin

This is not a complete list of alteplase drug interactions. Ask your doctor or pharmacist for more information

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Alteplase falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

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

It is not known if alteplase 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 alteplase.

Take alteplase exactly as prescribed.

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

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.

Absorption

Onset

Thrombolysis of the infarct-related coronary artery usually occurs <1 hour after initiation of therapy.30 31 39 40 Lysis of pulmonary emboli usually occurs within 2–6 hours after initiation of therapy.86 87 88 91

Distribution

Extent

Not known whether alteplase crosses the placenta or distributes into milk or the CNS.3

Elimination

Metabolism

Cleared principally by the liver,1 3 5 8 9 10 12 27 46 130 131 which subsequently releases degradation products into the blood.10 11 27 130 131

Elimination Route

Excreted mainly in urine.130

Half-life

Patients with acute MI: mean 3.6–4.6 minutes for initial distribution phase (t½α) , mean 39–53 minutes for terminal elimination phase (t½β).65 Patients with thrombo-occlusive disease: mean 4.4 and 26.5 minutes for t½α and t½β, respectively.66

Special Populations

Prolonged elimination half-life in patients with severely impaired hepatic function and/or hepatic blood flow.46 185 221

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• Alteplase Recombinant
• Alteplase, Tissue Plasminogen Activator, Recombinant
• tPA

Activase:

Acute ischemic stroke: Treatment of acute ischemic stroke (AIS) as soon as possible but within 3 hours of symptom onset.

Pulmonary embolism: Management of acute massive pulmonary embolism (PE)

ST-elevation myocardial infarction: Management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in coronary arteries.

Limitations of use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose acute myocardial infarction (MI) puts them at low risk for death or heart failure.

Recommended criteria for treatment:

STEMI (ACCF/AHA [O’Gara 2013]): Ischemic symptoms within 12 hours of treatment or evidence of ongoing ischemia 12 to 24 hours after symptom onset with a large area of myocardium at risk or hemodynamic instability.

STEMI ECG definition: New ST-segment elevation at the J point in at least 2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2-V3 and/or of ≥1 mm (0.1 mV) in other contiguous precordial leads or limb leads. New or presumably new left bundle branch block (LBBB) may interfere with ST-elevation analysis and should not be considered diagnostic in isolation.

At non-PCI-capable hospitals, the ACCF/AHA recommends thrombolytic therapy administration when the anticipated first medical contact (FMC)-to-device time at a PCI-capable hospital is >120 minutes due to unavoidable delays.

AIS: Onset of stroke symptoms within 3 hours of treatment

Acute PE: Age ≤75 years: Documented massive PE (defined as acute PE with sustained hypotension [SBP <90 mm Hg for ≤15 minutes or requiring inotropic support], persistent profound bradycardia [HR <40 bpm with signs or symptoms of shock], or pulselessness); alteplase may be considered for submassive PE with clinical evidence of adverse prognosis (eg, new hemodynamic instability, worsening respiratory insufficiency, severe right ventricular (RV) dysfunction, or major myocardial necrosis) and low risk of bleeding complications. Note: Not recommended for patients with low-risk PE (eg, normotensive, no RV dysfunction, normal biomarkers) or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening (AHA [Jaff 2011]).

Cathflo Activase: Restoration of function to central venous access device

As with all drugs that may affect hemostasis, bleeding is the major adverse effect associated with alteplase. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the dosage administered, concurrent use of multiple agents that alter hemostasis, and patient predisposition. Rapid lysis of coronary artery thrombi by thrombolytic agents may be associated with reperfusion-related atrial and/or ventricular arrhythmia. Lowest rate of bleeding complications expected with dose used to restore catheter function.

>10%: Local: Catheter site hemorrhage (15%; accelerated administration)

1% to 10%:

Cardiovascular: Hypotension

Gastrointestinal: Gastrointestinal hemorrhage (5%), gastric ulcer with hemorrhage (4%), nausea, vomiting

Genitourinary: Genitourinary tract hemorrhage (4%)

Hematologic & oncologic: Hemorrhage (GUSTO trial; minor: 7%; major: <1%), bruise (1%)

Miscellaneous: Fever

<1% (Limited to important or life-threatening): Angioedema (orolingual), epistaxis, gingival hemorrhage, hypersensitivity reaction (including anaphylaxis, anaphylactoid reaction, laryngeal edema, skin rash, urticaria), intracranial hemorrhage (when adult dose is ≤100 mg), retroperitoneal hemorrhage

Additional events associated with use in STEMI: Asystole, atrioventricular block, atrioventricular dissociation, bradycardia, cardiac failure, cardiac tamponade, cardiogenic shock, ischemia (recurrent), mitral valve insufficiency, myocardial reinfarction, myocardial rupture, pericardial effusion, pericarditis, pulmonary edema, seizure, thromboembolism, ventricular tachycardia

Additional events associated with use in pulmonary embolism: Pleural effusion, pulmonary edema, pulmonary embolism (re-embolization), thromboembolism

Additional events associated with use in stroke: Cerebral edema, cerebral herniation, cerebrovascular accident (new ischemic stroke), seizure

Acute ischemic stroke (AIS): Baseline: Neurologic examination, head CT (without contrast), blood pressure, CBC, aPTT, PT/INR, glucose. During and after initiation: In addition to monitoring for bleeding complications, the 2013 AHA/ASA guidelines for the early management of AIS recommends the following:

Perform neurological assessments every 15 minutes during infusion and every 30 minutes thereafter for the next 6 hours, then hourly until 24 hours after treatment.

If severe headache, acute hypertension, nausea, or vomiting occurs, discontinue the infusion and obtain emergency CT scan.

Measure BP every 15 minutes for the first 2 hours of initiation then every 30 minutes for the next 6 hours, then hourly until 24 hours after initiation of alteplase. Increase frequency if a systolic BP is ≥180 mm Hg or if a diastolic BP is ≥105 mm Hg; administer antihypertensive medications to maintain BP at or below these levels.

Obtain a follow-up CT scan at 24 hours before starting anticoagulants or antiplatelet agents.

Central venous catheter clearance: Assess catheter function by attempting to aspirate blood.

Pulmonary embolism: Monitor BP and HR continually and for at least 24 hours after administration; assess invasive catheters hourly for bleeding (Smithburger 2013).

ST-elevation MI: Baseline: Blood pressure, serum cardiac biomarkers, CBC, PT/INR, aPTT. During and after initiation: Assess for evidence of cardiac reperfusion through resolution of chest pain, resolution of baseline ECG changes, preserved left ventricular function, cardiac enzyme washout phenomenon, and/or the appearance of reperfusion arrhythmias; assess for bleeding potential through clinical evidence of GI bleeding, hematuria, gingival bleeding, fibrinogen levels, fibrinogen degradation products, PT and aPTT.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), skin discoloration to blue, black, or purple, angina, severe dizziness, passing out, severe headache, severe muscle pain, severe abdominal pain, or catheter site pain or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Occluded IV catheter: Infuse in to catheter, do not infuse in to patient: Dose listed is per lumen; for multilumen catheters, treat one lumen at a time; dose should always be aspirated out of catheter after dwell.
Manufacturer's recommendations (CathFlo Activase):
Central venous catheter: post natal age 14 days or older: Use a 1 mg/mL concentration; instill a volume equal to 110% of the internal lumen volume of the catheter; do not exceed 2 mg in 2 mL; leave in lumen for up to 2 hours, then aspirate out of catheter; may instill a second dose if catheter remains occluded after 2 hour dwell time.
Alternative dosing:
Central venous catheter: 0.5 mg diluted in NS to a volume equal to the internal volume of the lumen; instill in each lumen over 1-2 minutes; leave in lumen for 1 to 2 hours, then aspirate out of catheter; flush catheter with NS.
or
Central venous catheter: 0.25 to 0.5 mg/mL solution; instill a volume to fill the catheter; leave in lumen for up to 2 hours, then aspirate out of catheter.

Data not available