Anticoagulants -

A potential risk exists when alteplase is used concomittantly with heparin and Vitamin K antagonists

Drugs affecting platelet function- drugs that alter platelet function (ie. aspirin, dipyridamole and abcimab ) may increase risk of bleeding if administered prior to or after alteplase therapy.

Nitroglycerin- concomittant use decreases alteplase conc. therefore, decreasing thrombolytic effect.

Avoid use of notroglycerin with alteplase

Acute myocardial infarction

AMI Acute ischemic stroke- AIS

Pulmonary embolism - PE

Bleeding ( most frequent ) - should serious bleeding in a critical location ( intracranial, GI, retroperitoneal, pericardial, ) occur immediately discontinue alteplase therapy, along with concomittant theraspy with heparin.

Accelarated infusion- the incidence of all strokes as well as that of haemorhage stroke , increased with increasing age.

Hypersensitivity- anaphylactoid reactions, laryngeal edema, orolingual angioedema, rash, and urticaria have been reported. Most cases resolved with prompt treatment .

Other adverse reactions- AMI- arrhythmias, AV block, cardiogenic shock, heart failure, cardiac arrest, recurrent ischemia, myocardial infarction,

PE- pulmonary re-embolism, pulmonary edema, pleural efusion, thromboembolism, hypotension, fever AIS- cerebral edema, cerbral herniation, seizure, new ischemic stroke

Hypersentivity to the drug or to the components

AMI- evidence of ICH on pretreatment evaluation, suspicion of subarachoid hemorhage, recent (within 3 mths ) intracranial or intraspinal surgery, serous head trauma, or previous stroke.

Bleeding diathessis- includes but not limited to - current use of oral anticoagulants eg. warfarin sodium with prothrombin time PT longer tan 15 seconds, admin. of heparin within 48 hrs prceeding stroke onset with elevated activated partial thromboplastin time aPTT at presentatin , platelet county below 100,000 mm2.

Warnings

Bleeding- concomittant use of heparin anticoagulation may contribute to the bleeding If serious bleeding ( not controllable by local pressure ) occurs, imediately terminate alteplase infusion and comcomittant heparin.

Cholestrol embolism- has been reported rarely in patients treated with all thrombolytic agents, the incidence is unknown. This serious condition which can be lethal, is associated with invasive vascular procedures.

Arrhythmias- coronary thrombosis may result in arrhthymias associated with reperfusion. Have antiarrhythmic therapy for bradycardia or ventricular irritability available when alteplase infusions are administered.

Pregnancy- Use during pregnancy if potential benefit justifies the ptential risk to the fetus.

Lactation- Excercise caution when administering to nursing women

Children- Safey and efficacy of alteplase in pediatric patients have not been established.

Lab test abnormalites- during therapy if coagulation tests or measures of fibrolytic activity are performed the resultsmay be unreliable unless specific precautions are taken to prevent in vitro artifacts.

Aleplase present in blood in pharmacogical conc. remains active in vitro. This can lead to degradation of fibrinogen in blood samles removed for analysis.

Collection of blood samples in presence of aprotonin ( 150 to 200 units/ml) may to some extent mitigate the phenomenon.

Indication-

Acute myocardial infarction AMI

Acute ischemic stroke- AIS

Pulmonary embolism - PE

Dosage-

For IV admin. only AMI- administer as soon as possible after the onset of symptoms. Do not use of 150mg because it has been associated with an increase of intracranial bleeding.

Pharmacology

Alteplase, a tissue plasminogen activator tPA produced by recombinant DNA is synthesised using the complimentary DNA for natural human-tisue type plasminogen activator obtained from a human melanoma cell line. Biologically potency , determined by an in vitro activity is 580,000 units/mg.

Pharmacokinetics

Because of its large molecular size alteplase cannot diffuse across biological membranes and must be given parentrally , usually IV. Maximal plasma conc. of 3 to 4mg/L are acheived after standard admin. of 90 to 100mg doses.

Steady state conc. for initial infusion period were 45% higher when administered in an accelrated regimen. Alteplase is cleared rapidly from plasma at a rate of 380 to 570 mL/min, primarilly by the liver.

More than 50% of the drug present in plasma is cleared within 5 minutes after the infusion has been terminated, and approx, 80% is cleared within 10 minutes

Pregnancy

Use during pregnancy if potential benefit justifies the ptential risk to the fetus.

Lactation

Excercise caution when administering to nursing women

Children-

Safey and efficacy of alteplase in pediatric patients have not been established