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
Novastan Side Effects, and Drug Interactions - Argatroban
Novastan Side Effects, and Drug Interactions - Argatroban
SIDE EFFECTS
Adverse Events Reported in HIT/HITTS Patients
The following safety information is based on all 568 patients treated with
Argatroban in Study 1 and Study 2. The safety profile of the patients from these
studies is compared with that of 193 historical controls in which the adverse
events were collected retrospectively. The adverse events reported in this section
include all events regardless of relationship to treatment. Adverse events are
separated into hemorrhagic and non-hemorrhagic events.
Major bleeding was defined as bleeding that was overt and associated with a
hemoglobin decrease ≥2 g/dL, that led to a transfusion of ≥2 units,
or that was intracranial, retroperitoneal, or into a major prosthetic joint.
Minor bleeding was overt bleeding that did not meet the criteria for major bleeding.
Table 3 gives an overview of the most frequently observed hemorrhagic events,
presented separately by major and minor bleeding, sorted by decreasing occurrence
among Argatroban-treated patients.
Table 3. Major and Minor Hemorrhagic Adverse Events
|
|
Major Hemorrhagic Events * |
|
|
Study 1 & Study 2
(All Argatroban-
treated patients)
(n=568) |
Historical
Control
(n=193) |
|
|
% |
% |
|
Gastrointestinal
|
2.3 |
1.6 |
|
Genitourinary and hematuria
|
0.9 |
0.5 |
|
Decrease in hemoglobin and hematocrit
|
0.7 |
0 |
|
Multisystem hemorrhage and DIC
|
0.5 |
1 |
|
Limb and BKA stump
|
0.5 |
0 |
|
Intracranial hemorrhage
|
0 |
0.5 |
|
|
Minor Hemorrhagic Events * |
|
|
Study 1 & Study 2
(All Argatroban-
treated patients)
(n=568) |
Historical
Control
(n=193) |
|
|
% |
% |
|
Gastrointestinal
|
14.4 |
18.1 |
|
Genitourinary and hematuria
|
11.6 |
0.8 |
|
Decrease in hemoglobin and hematocrit
|
10.4 |
0 |
|
Groin
|
5.4 |
3.1 |
|
Hemoptysis
|
2.9 |
0.8 |
|
Brachial
|
2.4 |
0.8 |
|
*Patients may have experienced more than one event.
DIC = disseminated intravascular coagulation.
BKA = below the knee amputation.
|
Table 4 gives an overview of the most frequently observed non-hemorrhagic events
sorted by decreasing frequency of occurrence ( ≥2%) among Argatroban-treated
patients.
Table 4. Non-hemorrhagic Adverse Events *
|
|
Study 1 & Study 2
(All Argatroban-
treated patients)
(n=568) |
Historical
Control
(n=193) |
|
|
% |
% |
|
Dyspnea
|
8.1 |
8.8 |
|
Hypotension
|
7.2 |
2.6 |
|
Fever
|
6.9 |
2.1 |
|
Diarrhea
|
6.2 |
1.6 |
|
Sepsis
|
6.0 |
12.4 |
|
Cardiac arrest
|
5.8 |
3.1 |
|
Nausea
|
4.8 |
0.5 |
|
Ventricular tachycardia
|
4.8 |
3.1 |
|
Pain
|
4.6 |
3.1 |
|
Urinary tract infection
|
4.6 |
5.2 |
|
Vomiting
|
4.2 |
0 |
|
Infection
|
3.7 |
3.6 |
|
Pneumonia
|
3.3 |
9.3 |
|
Atrial fibrillation
|
3.0 |
11.4 |
|
Coughing
|
2.8 |
1.6 |
|
Abnormal renal function
|
2.8 |
4.7 |
|
Abdominal pain
|
2.6 |
1.6 |
|
Cerebrovascular disorder
|
2.3 |
4.1 |
|
*Patients may have experienced more than one event.
|
Adverse Events Reported in Other Populations
The following safety information is based on a total of 1,127 individuals who
were treated with Argatroban in clinical pharmacology studies (n=211) or for
other clinical indications (n=916).
Intracranial Bleeding. In the HIT/HITTS population, intracranial bleeding
was not observed. Intracranial bleeding only occurred in patients with acute
myocardial infarction who were started on both Argatroban and thrombolytic therapy
with streptokinase. The overall frequency of this potentially life-threatening
complication among patients receiving both Argatroban and thrombolytic therapy
(streptokinase or tissue plasminogen activator) was 1% (8 out of 810 patients).
Intracranial bleeding was not observed in 317 subjects or patients who did not
receive concomitant thrombolysis (see WARNINGS).
Allergic Reactions. 156 allergic reactions or suspected allergic reactions
were observed in 1,127 individuals who were treated with Argatroban in clinical
pharmacology studies or for other clinical indications. About 95% (148/156)
of these reactions occurred in patients who concomitantly received thrombolytic
therapy (e.g., streptokinase) for acute myocardial infarction and/or contrast
media for coronary angiography.
Allergic reactions or suspected allergic reactions in populations other than
HIT patients include (in descending order of frequency * ):
- Airway reactions (coughing, dyspnea): 10% or more
- Skin reactions (rash, bullous eruption): 1 to <10%
- General reactions (vasodilation): 1 to 10%
* The CIOMS (Council for International Organization of Medical Sciences) III standard
categories are used for classification of frequencies.
DRUG INTERACTIONS
Heparin: Since heparin is contraindicated in patients
with heparin-induced thrombocytopenia, the co-administration of Argatroban and
heparin is unlikely for this indication. However, if Argatroban is to be initiated
after cessation of heparin therapy, allow sufficient time for heparin's effect
on the aPTT to decrease prior to initiation of Argatroban therapy.
Aspirin/Acetaminophen: Pharmacokinetic or pharmacodynamic
drug-drug interactions have not been demonstrated between Argatroban and concomitantly
administered aspirin (162.5 mg orally given 26 and 2 hours prior to initiation
of Argatroban 1 µg/kg/min. over 4 hours) or acetaminophen (1000 mg orally given
12, 6 and 0 hours prior to, and 6 and 12 hours subsequent to, initiation of
Argatroban 1.5 µg/kg/min. over 18 hours).
Oral anticoagulant agents: Pharmacokinetic drug-drug
interactions between Argatroban and warfarin (7.5 mg single oral dose) have
not been demonstrated. However, the concomitant use of Argatroban and warfarin
(5-7.5 mg initial oral dose followed by 2.5-6 mg/day orally for 6-10 days) results
in prolongation of the prothrombin time (PT) and International Normalized Ratio
(INR) (see CLINICAL PHARMACOLOGYand DOSAGE AND ADMINISTRATION ).
Thrombolytic agents: The safety and effectiveness
of Argatroban with thrombolytic agents have not been established (see ADVERSE
REACTIONS, Intracranial Bleeding ).
Co-administration: Concomitant use of Argatroban
with antiplatelet agents, thrombolytics, and other anticoagulants may increase
the risk of bleeding (see WARNINGS). Drug-drug interactions have not
been observed between Argatroban and digoxin or erythromycin (see CLINICAL
PHARMACOLOGY, Drug-Drug Interactions ).
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