A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Activase Side Effects, and Drug Interactions - Alteplase
Activase Side Effects, and Drug Interactions - Alteplase
SIDE EFFECTS
Bleeding
The most frequent adverse reaction
associated with Activase®, Alteplase,
recombinant in all approved
indications is bleeding (see
WARNINGS)14,15.
Should serious bleeding
in a critical location (intracranial,
gastrointestinal, retroperitoneal, pericardial) occur, Activase therapy
should be discontinued immediately, along with any concomitant
therapy with heparin. Death
and permanent disability
are not uncommonly reported in patients that have experienced stroke
(including intracranial
bleeding) and other serious bleeding episodes.
In the GUSTO trial for the treatment
of acute myocardial
infarction, using the accelerated infusion
regimen the incidence
of all strokes for the Activase-treated patients 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. The incidence
of all strokes, as well as that for hemorrhagic stroke, increased with
increasing age (see CLINICAL
PHARMACOLOGY: Accelerated Infusion in AMI
Patients). Data from previous trials utilizing a 3-hour infusion
of ¾ 100 mg indicated that
the incidence of total stroke
in six randomized double-blind placebo controlled trials2,7-11,16
was 1.2% (37/3161) in Alteplase-treated patients compared with 0.9% (27/3092)
in placebo-treated patients.
For the 3-hour infusion
regimen, the incidence of
significant internal bleeding
(estimated as > 250 cc blood
loss) has been reported in studies in over 800 patients. These data do
not include patients treated with the Alteplase accelerated infusion.
|
Total Dose ¾100 mg
|
| gastrointestinal |
5% |
| genitourinary |
4% |
| ecchymosis |
1% |
| retroperitoneal |
< 1% |
| epistaxis |
<1% |
| gingival |
<1% |
The incidence of intracranial
hemorrhage (ICH) in acute
myocardial infarction patients
treated with Activase is as follows:
| Dose |
Number of Patients |
ICH (%) |
| 100 mg, 3-hours |
3272 |
0.4 |
| ¾ 100 mg, accelerated |
10,396 |
0.7 |
| 150 mg |
1779 |
1.3 |
| 1-1.4 mg/kg |
237 |
0.4 |
These data indicate that a dose
of 150 mg of Activase should not
be used in the treatment
of AMI because it has been associated
with an increase in intracranial
bleeding17.
For acute massive
pulmonary embolism,
bleeding events were consistent
with the general safety profile
observed with Activase in acute
myocardial infarction patients receiving the 3-hour infusion
regimen.
The incidence of I.H.
especially symptomatic
I.H. in patients with acute ischemic
stroke was higher in Activase-treated
patients than placebo patients
(see CLINICAL PHARMACOLOGY).
A study of another alteplase product, Actilyse, in acute
ischemic stroke, suggested that doses greater than 0.9 mg/kg may be associated
with an increased incidence of ICH18.
Doses greater than 0.9 mg/kg (maximum 90 mg) should not be used in
the management of acute ischemic
stroke.
Bleeding events other than ICH were noted in the studies of acute
ischemic stroke and were consistent with the general safety profile
of Activase. In The NINDS t-PA Stroke Trial (Parts 1 and 2), the frequency
of bleeding requiring red blood
cell transfusions was 6.4% for
Activase-treated patients compared to 3.8% for placebo
(p = 0.19, using Mantel-Haenszel Chi-Square).
Fibrin which is proof of the hemostatic
plug formed at needle
puncture sites will be lysed
during Activase therapy. Therefore, Activase therapy requires careful
attention to potential
bleeding sites, e.g., catheter
insertion sites, and arterial
puncture sites.
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 Activase therapy
has not been established. When such reactions occur, they usually respond
to conventional therapy.
Other Adverse REACTIONS
Patients with myocardial
infarction or pulmonary
embolism 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 can be life-threatening and 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
Activase therapy.
DRUG INTERACTIONS
The interaction of Activase with other cardioactive
or cerebroactive drugs has not been studied. In
addition to bleeding
associated with heparin and vitamin
K antagonists, drugs that alter platelet
function (such as acetylsalicylic
acid, dipyridamole and Abciximab)
may increase the risk of bleeding
if administered prior to, during, or after Activase therapy.
Use of Antithrombotics
Aspirin and heparin have
been administered concomitantly with and following infusions of Activase
in the management of acute myocardial
infarction or pulmonary
embolism. Because heparin, aspirin, or Activase may cause bleeding complications,
careful monitoring for bleeding
is advised, especially at arterial
puncture sites.
The concomitant use of
heparin or aspirin
during the first 24 hours following symptom
onset were prohibited in The NINDS t-PA Stroke Trial. The safety of such
concomitant use with Activase
for the management of acute ischemic stroke
is unknown.
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