Drug Interaction:
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
Indication:
Acute myocardial infarction
AMI Acute ischemic stroke- AIS
Pulmonary embolism - PE
Adverse Reaction:
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
Contra-Indications:
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.
Dosages/ Overdosage Etc:
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.
Patient Information:
Ref - USP PDI Vol II 17th Edition (1997)
THROMBOLYTIC AGENTS - SYSTEMIC
ALTREPLASE
ANISTREPLASE
STREPTOKINASE
UROKINASE
1.Allergies-
Tell your doctor if you have ever had any unusual or allergic reaction to
alteplase, anisstreplase, streptokinase, or urokinase. Also tell your
healthcare care professional if you are allergic to any other substances
such as foods. preservatives or dyes.
2.Pregnancy-
Tell your doctor if you are pregnant or have recently delivered a baby.
There is a slight chance that use of thrombolytic agents during the first
five months of pregnancy may cause miscarriage.
Consult your doctor before your take these medicines.
3. Breast-feeding-
It is not known whether thrombolytic medicines pass into breast milk.
Mothers who are taking this medicine and who wish to breast feed
should discuss this with their doctor.
4.Children-
This medicine has been tested in a limited number of children and in
effective doses the medicine has not been shown to cause different
side effects or problems than it does in adults.
5.Older adults-
The need for treatment with a thrombolytic agent may be increased in
elderly patients with blood clots.However, the chance of bleeding
may also be increased. It is important that you discuss this with your
doctor.
6. Other medicines-
Although certain medicines should not be used together at all, in other
cases two different medicines may be used together even if an
interaction might occur.
In such cases your doctor may want to change the dose, or other
precautions may be necessary.
Tell your doctor if you are using any using any other prescription or
medicines.
7. Other medical problems-
The presence of other medical problems may affect the use of
thrombolytic agents. Make sure you tell your doctor if you have
any other medical problems
Pharmacology/ Pharmacokinetics:
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 and lactation:
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
Manufacturer Details