Action And Clinical Pharmacology:
Alteplase is a serine protease which has the property of
fibrin-enhanced conversion of plasminogen to plasmin. It produces
minimal conversion of plasminogen in the absence of fibrin; and when
introduced into the systemic circulation, alteplase binds to fibrin in a
thrombus and converts the entrapped plasminogen to plasmin. This
initiates local fibrinolysis with minimal systemic effects. Following
administration of alteplase there is a decrease (20 to 30%) in
circulating fibrinogen. Decreases in plasminogen and a2-antiplasmin are
also evident.
Alteplase is cleared rapidly from circulating plasma with an initial
half-life of less than 5 minutes. There is no difference in the dominant
initial plasma half-life between the 3-hour and accelerated regimens
for acute myocardial infarction (AMI). The plasma clearance of alteplase
is approximately 500 mL/min. The clearance is mediated primarily by the
liver.
An occlusive thrombus is present in the infarct-related coronary artery
in approximately 80% of patients experiencing a transmural myocardial
infarction evaluated within 4 hours of onset of symptoms.
Acute Myocardial Infarction Patients: Two alteplase dose regimens have
been studied in patients experiencing AMI: accelerated infusion, and
3-hour infusion. The comparative efficacy of these 2 regimens has not
been evaluated.
90-Minute Accelerated Infusion in Patients with Acute Myocardial
Infarction: Accelerated infusion of alteplase was studied in an
international, multicentre trial (GUSTO) where 41 021 patients with
acute myocardial infarction were randomized to 4 thrombolytic regimens:
accelerated infusion of alteplase (<100 mg over 90 minutes) plus i.v.
heparin; streptokinase (1.5´10units over 60 minutes) plus i.v. heparin;
streptokinase (1.5´10units over 60 minutes) plus s.c. heparin; or
combined alteplase (1.0 mg/kg over 60 minutes) plus streptokinase
(1.0´10units over 60 minutes). ASA was administered daily. The results
are shown in Table I. The 30-day mortality for the accelerated infusion
of alteplase was 1% lower (14% relative risk reduction) than for
streptokinase (i.v. or s.c. heparin). In addition, the combined
incidence of 30-day mortality or nonfatal stroke for accelerated
alteplase was 1% lower (12% relative risk reduction) than for
streptokinase (i.v. heparin) and 0.8% lower (10% relative risk
reduction) than for streptokinase (s.c. heparin). Once a year follow-up
data suggest a sustained mortality benefit.
Subgroup analysis of patients by age, infarct location, and time from
symptom onset to thrombolytic treatment showed consistently lower 30-day
mortality for the group receiving the accelerated infusion of
alteplase. For patients who were over 75 years of age, a predefined
subgroup consisting of 12% of patients enrolled, the incidence of stroke
was 4.0% for the group receiving the accelerated infusion of alteplase,
2.8% for streptokinase (i.v. heparin), and 3.2% for streptokinase (s.c.
heparin); the incidence of combined 30-day mortality or nonfatal stroke
was 20.6% for accelerated infusion of alteplase, 21.5% for
streptokinase (i.v. heparin), and 22.0% for streptokinase (s.c.
heparin).
In-hospital events in the overall patient population, as well as events
in patients who survived beyond 30 days are shown in Table II.
An angiographic substudy of the GUSTO trial provided data on
infarct-related artery patency. Results are shown in Table III.
Reocclusion rates were similar for all 3 treatment regimens.
3-Hour Infusion in Patients with Acute Myocardial Infarction: In
patients studied with coronary angiography prior to and following
infusion of alteplase, the use of alteplase resulted in reperfusion of
documented obstructed vessels within 90 minutes after the commencement
of thrombolytic therapy in approximately 70% of patients. In 2 studies
involving 145 patients, alteplase produced reperfusion in 73% of
patients who received 70 to 100 mg (40.6 to 58´10IU) over 90 minutes. In
2 double blind randomized controlled trials in patients with AMI, the
patients infused with 80 to 100 mg of alteplase experienced improved
ventricular function and reduced incidence of clinical congestive heart
failure compared to those treated with placebo.
In a double-blind study involving 5 013 patients (ASSET Study) where
patients were infused with either alteplase or placebo within 5 hours of
onset of symptoms of AMI, improved 30-day survival was shown in
patients receiving alteplase compared to placebo. At 1 month, the
overall mortality rates were 7.2% for the alteplase-treated group and
9.8% for the placebo-treated group (p=0.001). This benefit was
maintained at 6 months (10.4% and 13.1% for alteplase and
placebo-treated patients respectively, p=0.008).
In the LATE study involving 5 711 patients where patients were infused
with either alteplase (100 mg over 3 hours) or placebo within 6 to 24
hours of onset of AMI symptoms, the 35-day mortality rates were 8.9% for
Activase rt-PA treated patients and 10.3% for placebo-treated patients
(p=not significant). Prespecified survival analysis according to
treatment within 12 hours of symptom onset showed a significant
reduction in mortality for the alteplase treated patients, 8.9% versus
12.0% for the placebo treated patients (p=0.0229).
Indications And Clinical Uses:
For i.v. use in adults for: the lysis of suspected occlusive coronary
artery thrombi associated with evolving transmural myocardial
infarction; and the reduction of mortality associated with AMI, the
improvement of ventricular function following AMI and the reduction in
the incidence of congestive heart failure.
Treatment should be initiated as soon as possible after the onset of
acute myocardial symptoms. Greater benefit appears to be associated with
earlier treatment of alteplase, following the onset of symptoms.
Alteplase is effective in patients in whom therapy is initiated within 6
hours of onset of symptoms for the accelerated infusion regimen or up
to 12 hours after onset of symptoms for the 3-hour infusion regimen. The
GUSTO study was designed to enrol patients within a 6-hour period
following the onset of myocardial infarct symptoms. The data available
from this trial are insufficient to support a recommendation for use of
the accelerated infusion regimen in patients presenting more than 6
hours after the onset of symptoms.
Contra-Indications:
Because thrombolytic therapy increases the risk of bleeding,
alteplase is contraindicated in the following situations: active
internal bleeding; history of stroke; patients receiving other i.v.
thrombolytic agents; recent (within 2 months) intracranial, or
intraspinal surgery or trauma (see Warnings); intracranial neoplasm,
arteriovenous malformation, or aneurysm; known bleeding diathesis;
severe uncontrolled hypertension, i.e., diastolic BP³110 mm Hg and/or
systolic BP³180 mm Hg; recent traumatic cardiopulmonary resuscitation;
recent severe trauma. tag_WarningWarnings
Manufacturers' Warnings In Clinical States:
Bleeding: The most common complication encountered during therapy
with alteplase is bleeding. The type of bleeding associated with
thrombolytic therapy can be divided into 2 broad categories: internal
bleeding involving the gastrointestinal tract, genitourinary tract,
respiratory tract, retroperitoneal or intracranial sites; superficial or
surface bleeding, observed mainly at invaded or disturbed sites (e.g.,
venous cutdowns, arterial punctures, sites of recent surgical
intervention).
The concomitant use of heparin anticoagulation contributes to the risk of bleeding.
Fibrin will be lysed during the infusion of alteplase and bleeding from
recent puncture sites may occur. Therefore, therapy with alteplase, as
with other thrombolytic agents, requires careful attention to all
potential bleeding sites (including catheter insertion sites, arterial
and venous puncture sites, cutdown sites and needle punctures sites).
I.M. injections and nonessential handling of the patient should be
avoided during and immediately following treatment with alteplase.
Venipunctures should be performed carefully and only as required.
Should an arterial puncture be necessary during an infusion of
alteplase, it is preferable to use an upper extremity vessel that is
accessible to manual compression. Pressure should be applied for at
least 30 minutes, a pressure dressing applied and the puncture site
checked frequently for evidence of bleeding.
Should serious bleeding in a critical location (not controllable by
local pressure) occur, the infusion of alteplase and any other
concomitant anticoagulant should be discontinued immediately and
treatment initiated (see Overdose: Symptoms and Treatment).
In the following conditions, the risks of alteplase therapy may be
increased and should be weighed against the anticipated benefits: recent
(within 10 days) major surgery, e.g., coronary artery bypass graft,
obstetrical delivery, organ biopsy, previous puncture of noncompressible
vessels; clinical evidence or history of transient ischemic attacks;
recent gastrointestinal or genitourinary bleeding (with 10 days); recent
trauma (within 10 days); a history or clinical evidence of hypertensive
disease in a patient over 70 years old; advanced age, e.g., over 75
years old; high likelihood or known presence of left heart thrombus,
e.g., mitral stenosis with atrial fibrillation; apical MI, with
thrombus; acute pericarditis; subacute bacterial endocarditis;
hemostatic defects including those secondary to severe hepatic or renal
disease; significant liver dysfunction, e.g., prolonged prothrombin
time; pregnancy; diabetic hemorrhagic retinopathy, or other hemorrhagic
ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at
seriously infected site; patients currently receiving oral
anticoagulants, e.g., warfarin sodium; any other condition in which
bleeding constitutes a significant hazard or would be particularly
difficult to manage because of its location.
Cholesterol Embolization: Cholesterol embolization has been reported
rarely in patients treated with all types of thrombolytic agents; the
true incidence is unknown. This serious condition, which can be lethal,
is also associated with invasive vascular procedures (e.g., cardiac
catheterization, angiography, vascular surgery) and/or anticoagulant
therapy. Clinical features of cholesterol embolism include livedo
reticularis, "purple toe" syndrome, acute renal failure, gangrenous
digits, hypertension, pancreatitis, myocardial infarction, cerebral
infarction, spinal cord infarction, retinal artery occlusion, bowel
infarction, and rhabdomyolysis.
Arrhythmias: Coronary thrombolysis may result in arrhythmias associated
with reperfusion. These arrhythmias (such as sinus bradycardia,
accelerated idioventricular rhythm, ventricular premature
depolarizations, ventricular tachycardia) are not different from those
often seen in the ordinary course of AMI and may be managed with
standard antiarrhythmic measures. It is recommended that antiarrhythmic
therapy for bradycardia and/or ventricular irritability be available
when infusions of alteplase are administered.
Use of Antithrombotics: ASA and heparin may be administered
concomitantly with and following infusions of alteplase. Because either
heparin, ASA or alteplase alone may cause bleeding complications,
careful monitoring for bleeding is advised, especially at arterial
puncture sites.
Precautions:
General: Alteplase should be administered in a hospital setting where
the appropriate diagnostic and monitoring techniques are readily
available.
Routine management of myocardial infarction should not be deferred after
evidence of successful thrombolysis is seen. Evaluation and management
of underlying atherosclerotic heart disease should be carried out as
clinically indicated.
Noncompressible arterial puncture must be avoided. Arterial and venous
punctures should be minimized. In the event of serious bleeding,
alteplase and heparin should be discontinued immediately. Heparin
effects can be reversed by protamine.
Drug Interactions:
The interaction of alteplase with other drugs has not been studied. In
addition to bleeding associated with heparin and warfarin, drugs that
alter platelet function (such as ASA) may increase the risk of bleeding
if administered prior to, during or after alteplase infusion.
Laboratory Tests: During alteplase infusion, coagulation tests and/or
measures of fibrinolytic activity may be performed if desired. However,
routine measurements of fibrinogen as well as fibrinogen degradation
products are unreliable, and should not be undertaken unless specific
precautions are taken to prevent in vitro artifacts. Alteplase is a
serine protease that when present in blood in pharmacologic
concentrations remains active under in vitro conditions. This can lead
to degradation of fibrinogen in a blood sample removed for analysis.
Collection of blood samples on aprotinin (150 to 200 units/mL) can to
some extent mitigate this phenomenon.
Geriatrics: The risks of therapy may be increased in the elderly (see Pharmacology, Warnings and Adverse Effects).
Children: Safety and effectiveness of alteplase in children has not been
established. Therefore treatment of such patients is not recommended.
Pregnancy: Reproduction studies have not been conducted with alteplase.
It is also not known whether alteplase can cause fetal harm when
administered to a pregnant woman. Alteplase should be given to a
pregnant woman only if clearly needed.
Lactation: It is not known whether alteplase is excreted in human milk.
Because many drugs are excreted in human milk, caution should be
exercised when alteplase is administered to a nursing woman.
Readministration: There has been little documentation of
readministration of alteplase. Readministration should be undertaken
with caution. Less than 0.5% of patients receiving single courses of
alteplase therapy have experienced transient antibody formation.
Nevertheless, if an anaphylactoid reaction occurs, the infusion should
be discontinued immediately and appropriate therapy initiated.
Adverse Reactions:
Bleeding: The most frequent adverse reaction associated with
alteplase is bleeding. The type of bleeding associated with thrombolytic
therapy can be divided into 2 broad categories: internal bleeding,
involving the gastrointestinal tract, genitourinary tract, respiratory
tract, retroperitoneal or intracranial sites; superficial or surface
bleeding, observed mainly at invaded or disturbed sites (e.g., venous
cutdowns, arterial punctures, sites of recent surgical intervention).
The incidence of all strokes for the accelerated alteplase regimen in
the GUSTO trial was 1.6%, while the incidence of nonfatal stroke was
0.9%. The incidence of hemorrhagic stroke was 0.7%, not all of which
were fatal. Data from previous trials utilizing a 3-hour infusion
indicates that the incidence of total stroke in 6 randomized
double-blind placebo controlled trials was 1.2% (37/3 161) in
alteplase-treated patients (£100 mg) compared with 0.9% (27/3 092) in
placebo-treated patients.
Although the incidence of all strokes, as well as that for hemorrhagic
stroke, increased with increasing age, treatment with accelerated
regimen of alteplase was still shown to reduce mortality in older
patients. For patients who were over 75 years of age, a predefined
subgroup consisting of 12% of patients enrolled, the incidence of stroke
was 4.0% for the accelerated regimen of alteplase group, 2.8% for
streptokinase (i.v. heparin), and 3.2% for streptokinase (s.c. heparin)
(see Table IV). However, combined 30-day mortality or nonfatal stroke
was 20.6% for accelerated regimen of alteplase, 21.5% for streptokinase
(i.v. heparin) and 22.0% for streptokinase (s.c. heparin) in the GUSTO
study.
The following incidence of significant internal bleeding (estimated as
³250 mL blood loss) has been reported in studies involving over 1 300
patients treated at all doses of alteplase, administered as a 3-hour
infusion regimen: gastrointestinal 5%, genitourinary 4%.
The following incidence of moderate or severe bleeding was reported when
£100 mg alteplase was administered by accelerated infusion to >10
000 patients [GUSTO study]: gastrointestinal 1.5%, genitourinary 0.5%.
Incidence of £1% of ecchymosis, retroperitoneal bleeding, epistaxis and
gingival bleeding has been reported in clinical studies involving
alteplase.
The incidence of intracranial bleeding in patients treated with up to
120 mg alteplase (3-hour infusion) has been 0.4%. At doses in excess of
120 mg (120 to 180 mg) the incidence of intracranial bleeding increased
to 1.3%. The incidence of intracranial bleeding in patients treated £100
mg alteplase (accelerated infusion, weight adjusted) was 0.7%. The
maximum total dose of alteplase should not exceed 100 mg.
Death and permanent disability have been reported in patients who have experienced stroke and other serious bleeding episodes.
Allergic Reactions: Allergic-type reactions, e.g., anaphylactoid
reaction, laryngeal edema, rash and urticaria have been reported very
rarely (<0.02%). A cause and effect relationship to alteplase therapy
has not been established.
Other Adverse Reactions: Patients with myocardial infarction can
experience disease-related events such as cardiogenic shock,
arrhythmias, pulmonary edema, heart failure, cardiac arrest, recurrent
ischemia, reinfarction, myocardial rupture, mitral regurgitation,
pericardial effusion, pericarditis, cardiac tamponade, venous thrombosis
and embolism, and electromechanical dissociation. These events may lead
to death. Other adverse reactions have been reported, principally
nausea and/or vomiting, hypotension, and fever. These reactions are
frequent sequelae of myocardial infarction and may or may not be
attributable to alteplase therapy.
Symptoms And Treatment Of Overdose:
Symptoms and Treatment: Overdosage could lead to serious bleeding.
Should serious bleeding occur in a critical location, the infusion of
alteplase and any other concomitant anticoagulant should be discontinued
immediately. If necessary, blood loss and reversal of the bleeding
tendency can be managed with whole blood or packed red cells. In the
event of clinically significant fibrinogen depletion, fresh frozen
plasma or cryoprecipitate can be infused. tag_DosageDosage
Dosage And Administration:
Alteplase is intended for i.v. use only. It should be given via a
dedicated i.v. line with an infusion pump. Extravasation of alteplase
infusion can cause ecchymosis and/or inflammation. Management consists
of terminating the infusion at the i.v. site and application of local
therapy.
Acute Myocardial Infarction: Administer alteplase as soon as possible after the onset of symptoms.
There are 2 dose regimens for alteplase for use in the management of
AMI. The comparative efficacy of these 2 regimens has not been
evaluated.
90-Minute Accelerated Infusion: See Table V. The recommended total dose
is based upon patient weight, not to exceed 100 mg. For patients
weighing >67 kg, the recommended dose is 100 mg, administered as a 15
mg i.v. bolus, followed by 50 mg infused over 30 minutes and then 35 mg
infused over the next 60 minutes.
For patients weighing <67 kg, the recommended dose is 15 mg
administered as an i.v. bolus, followed by 0.75 mg/kg to a maximum of 50
mg, infused over the next 30 minutes, and then 0.50 mg/kg to a maximum
of 35 mg infused over the next 60 minutes.
Preparation and Administration: The alteplase dose administered by
accelerated infusion may be prepared and administered as follows: A. The
bolus dose may be prepared in one of the following ways: 1. By removing
15 mL from the vial of reconstituted (1 mg/mL) alteplase using a
syringe and needle. For 50 mg vials, the syringe should not be primed
with air and the needle should be inserted into the alteplase vial
stopper. If the 100 mg vial is used, the needle should be inserted away
from the puncture mark made by the transfer device. 2. By removing 15 mL
from a port (second injection site) on the infusion line after the
infusion set is primed. 3. By programming an infusion pump to deliver a
15 mL (1 mg/mL) bolus at the initiation of the infusion. B. The
remainder of the alteplase dose may be administered as follows: 50 mg
vials: Administer using either a polyvinyl chloride bag or glass vial
and infusion set. 100 mg vials: Insert the spike end of an infusion set
through the same puncture site created by the transfer device in the
stopper of the vial of reconstituted alteplase. Hang the vial of
alteplase from the plastic molded capping attached to the bottom of the
vial.
3-Hour Infusion: The recommended dose is 100 mg administered as 60 mg
(34.8´10IU) in the first hour, of which 6 to 7 mg is administered as a
bolus over the first 1 to 2 minutes and the remainder is administered by
continuous infusion, 20 mg (11.6´10IU) by continuous infusion during
the second hour, and 20 mg (11.6´10IU) by continuous infusion over the
following 1 to 4 hours. For smaller patients (<65 kg), a dose of 1.25
mg/kg may be warranted. The alteplase dose administered by 3-hour
infusion may be prepared and administered as follows: A. The bolus dose
may be prepared in one of the following ways: 1. By removing 6 to 10 mL
from the vial of reconstituted (1 mg/mL) alteplase using a syringe and
needle. For 50 mg vials, the syringe should not be primed with air and
the needle should be inserted into the alteplase vial stopper. If the
100 mg vial is used, the needle should be inserted away from the
puncture mark made by the transfer device. 2. By removing 6 to 10 mL
from a port (second injection site) on the infusion line after the
infusion set is primed. 3. By programming an infusion pump to deliver a 6
to 10 mL (1 mg/mL) bolus at the initiation of the infusion. B. The
remainder of the alteplase dose may be administered as follows: 50 mg
vials: Administer using either a polyvinyl chloride bag or glass vial
and infusion set. 100 mg vials: Insert the spike end of an infusion set
through the same puncture site created by the transfer device in the
stopper of the vial of reconstituted alteplase. Hang the vial of
alteplase from the plastic molded capping attached to the bottom of the
vial.
Anticoagulation During and After Treatment with Alteplase: To date,
heparin has been administered concomitantly in more than 90% of patients
given alteplase. Adjunctive i.v. heparin administration is recommended
to obtain a therapeutic partial thromboplastin time (PTT). The infusion
of heparin should be initiated prior to the termination of the infusion
of alteplase.
Reconstitution and Dilution: Alteplase should be reconstituted by
aseptically adding to the vial, the appropriate volume of Sterile Water
for Injection, USP (50 mL for 50 mg vials, 100 mL for 100 mg vials). It
is important that alteplase be reconstituted only with Sterile Water for
Injection, USP, without preservatives. Do not use Bacteriostatic Water
for Injection. The reconstituted preparation results in a colorless to
pale yellow transparent solution containing alteplase 1 mg/mL at a pH of
7.3. The osmolality of this solution is approximately 215 mOsm/kg.
Before further dilution or administration, parenteral drug products
should be visually inspected for particulate matter and discoloration
prior to administration whenever solution and container permit. Because
alteplase contains no preservatives, it should be reconstituted
immediately before use (see Stability and Storage).
The reconstituted solution may be diluted further immediately before
administration to yield concentrations as low as 0.5 mg/mL in 0.9%
Sodium Chloride for Injection, USP or 5% Dextrose for Injection, USP.
Excessive agitation during dilution should be avoided; mixing should be
accomplished with gentle swirling and/or slow inversion. Do not use
other infusion solutions e.g., Sterile Water for Injection, USP, or
preservative containing solutions for further dilution.
No other medication should be added to alteplase solution. Solutions
should be administered as described above. Unused infusion solution
should be immediately discarded.
50 mg vials: Using a large bore needle (e.g., 18 gauge), and the
accompanying 50 mL Sterile Water for Injection, USP, direct the stream
of Sterile Water for Injection, USP into the lyophilized cake. Do not
use if vacuum is not present. Slight foaming upon reconstitution is not
unusual; standing undisturbed for several minutes is usually sufficient
to allow dissipation of any large bubbles. Excessive or vigorous
shaking should be avoided.
100 mg vials: Using the transfer device provided, the contents of the
accompanying 100 mL vial of Sterile Water for Injection, USP should be
added to the contents of the 100 mg vial of alteplase powder. Slight
foaming upon reconstitution is not unusual; standing undisturbed for
several minutes is usually sufficient to allow dissipation of any large
bubbles. No vacuum is present in 100 mg vials. Please refer to the
accompanying instructions for Reconstitution and Administration of the
100 mg vials:
1. Use aseptic technique throughout.
2. Remove the protection flip-caps from 1 vial of alteplase and 1 vial of Sterile Water for Injection, USP.
3. Open the package containing the transfer device by peeling the paper label off the package.
4. Remove the protective cap from one end of the transfer device and
keeping the vial of Sterile Water for Injection upright, insert the
piercing pin vertically into the centre of the stopper of the vial of
Sterile Water for Injection.
5. Remove the protective cap from the other end of the transfer device. Do not invert the vial of Sterile Water for Injection.
6. Holding the vial of alteplase upside-down, position it so that the
centre of the stopper is directly over the exposed piercing pin of the
transfer device.
7. Push the vial of alteplase down so that the piercing pin is inserted through the centre of the alteplase stopper.
8. Invert the 2 vials so that the vial of alteplase is on the bottom
(upright) and the vial of Sterile Water for Injection is upside-down,
allowing the Sterile Water for Injection to flow down through the
transfer device. Allow the entire contents of the vial of Sterile Water
for Injection to flow into the alteplase vial (approximately 0.5 mL of
Sterile Water for Injection will remain in the diluent vial).
Approximately 2 minutes are required for this procedure.
9. Remove the transfer device and the empty Sterile Water for Injection
vial from the alteplase vial. Safely discard both the transfer device
and the empty diluent vial according to institutional procedures.
10. Swirl gently to dissolve the alteplase powder. Do not shake.
Stability and Storage: Lyophilized alteplase is stable up to the
expiration date stamped on the vial when stored at controlled
temperatures between 2 and 30°C. Protect the lyophilized material during
extended storage from excessive exposure to light.
Unused reconstituted alteplase (in the vial) may be stored at 2 to 30°C
for up to 8 hours. After that time, any unused portion of the
reconstituted material should be discarded. During the period of
reconstitution and infusion, protection from light is not necessary.
Availability And Storage:
50 mg: Each vial of sterile, lyophilized powder contains: alteplase
50 mg. Nonmedicinal ingredients: L-arginine, phosphoric acid,
polysorbate 80. Phosphoric acid and/or sodium hydroxide may be used
prior to lyophilization for pH adjustment. Vials of 50 mg with vacuum
present. Boxes of 1 vial of Activase rt-PA 50 mg (29´10IU), and 1 vial
of Sterile Water for Injection, USP 50 mL, for preparing a sterile
solution of Activase rt-PA.
100 mg: Each vial of sterile, lyophilized powder contains: alteplase
100 mg. Nonmedicinal ingredients: L-arginine, phosphoric acid,
polysorbate 80. Phosphoric acid and/or sodium hydroxide may be used
prior to lyophilization for pH adjustment. Vials of 100 mg with no
vacuum present. Boxes of 1 vial of Activase rt-PA 100 mg (58 ´ 10IU) and
1 vial of Sterile Water for Injection, USP 100 mL, and 1 transfer
device for preparing a sterile solution of Activase rt-PA.
Biological potency is determined by an in vitro clot lysis assay and is expressed in International Units (58´10IU/mg alteplase).
ANISTREPLASE
Anistreplase (Eminase)
Anistreplase
Classification:
Thrombolytic enzyme
Action/Kinetics:
Prepared by acylating human plasma derived from lys-plasminogen and
purified streptokinase derived from group C beta-hemolytic streptococci.
When prepared, anistreplase is an inactive derivative of a fibrinolytic
enzyme although the compound can still bind to fibrin. Anistreplase is
activated by deacylation and subsequent release of the anisoyl group in
the blood stream. The production of plasmin from plasminogen occurs in
both the blood stream and the thrombus leading to thrombolysis. Lyses
thrombi obstructing coronary arteries and reduces the size of infarcts.
t
1/2: 70-120 min.
Uses:
Management of AMI in adults, resulting in improvement of ventricular
function and reduction of mortality. Treatment should be initiated as
soon as possible after the onset of symptoms of AMI.
Contraindications:
Use in active internal bleeding; within 2 months of intracranial or
intraspinal surgery; recent trauma, including cardiopulmonary
resuscitation; history of CVA; intracranial neoplasm; arteriovenous
malformation or aneurysm; known bleeding diathesis; severe, uncontrolled
hypertension; severe allergic reactions to streptokinase.
Special Concerns:
Use with caution in nursing mothers. Safety and effectiveness have not been determined in children.
NOTE: The risks of anistreplase therapy may be increased in the
following conditions; thus, benefit versus risk must be assessed prior
to use. Within 10 days of major surgery (e.g., CABG, obstetric delivery,
organ biopsy, previous puncture of noncompressible vessels);
cerebrovascular disease; within 10 days of GI or GU bleeding; within 10
days of trauma including cardiopulmonary resuscitation; SBP > 180 mm
Hg or DBP > 110 mm Hg; likelihood of left heart thrombus (e.g.,
mitral stenosis with atrial fibrillation); SBE; acute pericarditis;
hemostatic defects including those secondary to severe hepatic or renal
disease; pregnancy; clients older than 75 years of age; diabetic
hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions;
septic thrombophlebitis or occluded arteriovenous cannula at seriously
infected site; clients on oral anticoagulant therapy; any condition in
which bleeding constitutes a significant hazard or would be difficult to
manage due to its location.
Side Effects:
Bleeding: Including at the puncture site (most common), nonpuncture site hematoma, hematuria, hemoptysis,
GI hemorrhage, intracranial bleeding gum/mouth hemorrhage, epistaxis, anemia, eye hemorrhage.
CV:
Arrhythmias conduction disorders, hypotension;
cardiac rupture chest pain, emboli (causal relationship to use of anistreplase unknown).
Allergic:
Anaphylaxis, bronchospasm
angioedema, urticaria, itching, flushing, rashes, eosinophilia, delayed
purpuric rash which may be associated with arthralgia, ankle edema, mild
hematuria, GI symptoms, and proteinuria.
GI: N&V.
Hematologic: Thrombocytopenia.
CNS: Agitation, dizziness, paresthesia, tremor, vertigo.
Respiratory: Dyspnea, lung edema.
Miscellaneous: Chills, fever, headache, shock.
Laboratory Test Alterations:
 Transaminase levels, thrombin time, activated PTT, and PT.
 Plasminogen and fibrinogen.
Drug Interactions:
Increased risk of bleeding or hemorrhage if used with heparin, oral
anticoagulants, vitamin K antagonists, aspirin, or dipyridamole.
How Supplied:
Powder for injection: 30 U
Dosage
IV only: 30 units over 2-5 min into an IV line or vein as soon as possible after onset of symptoms.
STREPTASE
(streptokinase)
DESCRIPTION
Streptase®, Streptokinase, is a sterile, purified preparation of a bacterial protein elaborated by group C (beta) -hemolytic
streptococci. It is supplied as a lyophilized white powder containing
25 mg cross-linked gelatin polypeptides, 25 mg sodium L-glutamate,
sodium hydroxide to adjust pH, and 100 mg Albumin (Human) per vial or
infusion bottle as stabilizers. The preparation contains no
preservatives and is intended for intrvenous and intracoronary administration
Streptase Indications & Dosage
INDICATIONS
Acute Evolving Transmural Myocardial Infarction: Streptase, Streptokinase, is indicated for use in the management of AMI in adults, for the lysis of intracoronary thrombus , the improvement of ventricular function, and the reduction of mortality associated with AMI, when administered by either the intrvenous or the intracoronary route, as well as for the reduction of infarc size and CHF
associated with AMI when administered by the intravenous route. Earlier
administration of Streptokinase is correlated with greater clinical
benefit.
Pulmonary Embolism: Streptase, Streptokinase, is indicated for the lysis of objectively diagnosed (angiography
or lung scan) pulmonary emboli, involving obstruction of blood flow to a
lobe or multiple segments, with or without unstable hemodynamics.
Deep Vein Thrombosis: Streptase, Streptokinase, is indicated
for the lysis of objectively diagnosed (preferably ascending
venography), acute, extensive thrombi of the deep veins such as those
involving the popliteal and more proximal vessels.
Arterial Thrombosis or Embolism: Streptase, Streptokinase,
is indicated for the lysis of acute arterial thrombi and emboli.
Streptokinase is not indicated for arterial emboli originating from the
left side of the heart due to the risk of new embolic phenomena such as cerebral embolism.
Occlusion of Arteriovenous Cannulae: Streptase,
Streptokinase, is indicated as an alternative to surgical revision for
clearing totally or partially occluded arteriovenous cannulae when
acceptable flow cannot be achieved.
DOSAGE AND ADMINISTRATION
Acute Evolving Transmural Myocardial Infarction: Administer
Streptokinase as soon as possible after onset of symptoms. The greatest
benefit in mortality reduction was observed when Streptokinase was
administered within four hours, but statistically significant benefit
has been reported up to 24 hours.
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- 1,500,000 IU within 60 min.
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- 20,000 IU by bolus followed by 2,000 IU/min. for 60 min.
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Pulmonary Embolism, Deep Vein Thrombosis, Arterial Thrombosis or Embolism: Streptase,
Streptokinase, treatment should be instituted as soon as possible after
onset of the thrombotic event, preferably within 7 days. Any delay in
instituting lytic therapy to evaluate the effect of heparin
therapy decreases the potential for optimal efficacy. Since human
exposure to streptococci is common, antibodies to Streptokinase are
prevalent. Thus, a loading dose of Streptokinase sufficient to
neutralize these antibodies is required. A dose of 250,000 IU of
Streptokinase infused into a peripheral vein over 30 minutes has been found appropriate in over 90% of patients. Furthermore, if the thrombin time or any other parameter of lysis after 4 hours of therapy is not
significantly different from the normal control level, discontinue
Streptokinase because excessive resistance is present.
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- IV Infusion Dosage/Duration
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- 100,000 IU/hr for 24 hr (72 hrs if concurrent DVT is suspected).
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- Arterial Thrombosis or Embolism
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- 100,000 IU/hr for 24-72 hr
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