Alteplase

Coronary thrombolysis may result in reperfusion arrhythmias (eg, accelerated idioventricular rhythm) (Miller 1986).

Internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, respiratory) or external bleeding, especially at arterial and venous puncture, sites may occur (may be fatal). The total dose should not exceed 90 mg for acute ischemic stroke or 100 mg for acute myocardial infarction or pulmonary embolism. Doses ≥150 mg associated with significantly increased risk of intracranial hemorrhage compared to doses ≤100 mg. Bleeding risk is low. Monitor all potential bleeding sites; if serious bleeding occurs, the infusion of alteplase and any other concurrent anticoagulants (eg, heparin) should be stopped.

Has been reported rarely in patients treated with thrombolytic agents; 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.

Although typically mild and transient, orolingual angioedema has occurred during and up to 2 hours after alteplase infusion in patients treated for AIS and STEMI. The use of concomitant ACE inhibitors and strokes involving the insular and frontal cortex are associated with an increased risk (Foster-Goldman 2013). The manufacturer recommends monitoring patients during and for several hours after infusion for orolingual angioedema. If angioedema develops, discontinue the infusion and promptly institute appropriate therapy. Disease-related concerns:

For the following conditions, the risk of bleeding is higher with use of thrombolytics and should be weighed against the benefits of therapy:

History of chronic, severe, poorly controlled hypertension; significant hypertension on presentation (systolic BP >180 mm Hg or diastolic BP >110 mm Hg); history of prior ischemic stroke >3 months; dementia; traumatic or prolonged CPR (>10 minutes); major surgery (• End-stage renal disease: In the treatment of AIS, according to the AHA/ASA 2016 scientific statement, alteplase use is recommended in patients with end-stage renal disease on hemodialysis who have a normal aPTT (very limited populations evaluated). Patients with an elevated aPTT may have an increased risk for hemorrhagic complications (AHA/ASA [Demaerschalk 2016]).

Appropriate use: Follow standard management for STEMI while infusing alteplase.

Appropriate use: Patients who present within 3 hours of stroke symptom onset should be treated with alteplase unless contraindications exist. A longer time window (3 to 4.5 hours after symptom onset) has been shown to be safe and efficacious for select individuals who meet ECASS III criteria (AHA/ASA [Demaerschalk 2016]; AHA/ASA [Jauch 2013]; Hacke 2008; Powers 2015). Concurrent drug therapy issues:

Use with caution in patients receiving oral anticoagulants; increased risk of bleeding. According to the AHA/ASA 2013 guidelines, in the treatment of acute ischemic stroke (AIS) within 3 hours of symptom onset, the current use of oral anticoagulants producing an INR >1.7, direct thrombin inhibitors, or direct factor Xa inhibitors with elevated sensitive laboratory test are contraindications. However, alteplase may be administered to patients with AIS having received direct thrombin inhibitors (eg, dabigatran) or direct factor Xa inhibitors (eg, rivaroxaban) when sensitive laboratory tests (eg, aPTT, INR, platelet count, ECT, TT, or appropriate direct factor Xa activity assays) are normal or the patient has not received a dose of these agents for >2 days (assuming normal renal function). When treating AIS 3 to 4.5 hours after symptom onset, the use of alteplase should be avoided with current use of any oral anticoagulant regardless of INR (AHA/ASA [Jauch 2013]). However, according to the AHA/ASA 2016 scientific statement, when treating AIS 3 to 4.5 hours after symptom onset, the use of alteplase appears safe and may be beneficial for patients taking warfarin with an INR • Aspirin: In the treatment of acute ischemic stroke, avoid aspirin for 24 hours following administration of alteplase; administration within 24 hours increases the risk of hemorrhagic transformation. According to the AHA/ASA 2016 scientific statement, alteplase is recommended for patients taking antiplatelet d

Concurrent heparin anticoagulation may contribute to bleeding. In the treatment of acute ischemic stroke, concurrent use of anticoagulants was not permitted during the initial 24 hours of the Special populations:

Use with caution in patients with advanced age (eg, >75 years); increased risk of bleeding. In the treatment of pulmonary embolism, age >75 years is considered a relative contraindication (Kearon 2012; Kearon 2016). In the treatment of acute ischemic stroke (within 3 to 4.5 hours after symptom onset), alteplase use in patients >80 years is considered an exclusion criteria (AHA/ASA [Jauch 2013]; Hacke 2008). However, according to the AHA/ASA 2016 scientific statement, alteplase use in patients >80 years with acute ischemic stroke presenting within 3 to 4.5 hours after symptom onset is safe and can be as effective as in younger patients (AHA/ASA [Demaerschalk 2016]).

Use with caution in pregnancy; increased risk of bleeding. Dosage form specific issues:

When used to restore catheter function, use Cathflo cautiously in those patients with known or suspected catheter infections. Evaluate catheter for other causes of dysfunction before use. Avoid excessive pressure when instilling into catheter.

Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling. Other warnings/precautions:

Intramuscular injections and nonessential handling of the patient should be avoided. Venipunctures should be performed carefully and only when necessary. Avoid internal jugular and subclavian venous punctures. If arterial puncture is necessary, use an upper extremity vessel that can be manually compressed.

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