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Argatroban (Argatroban) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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 HIT/HITTS patients.

Table 3. Major and Minor Hemorrhagic Adverse Events in HIT/HITTS Patients
Major Hemorrhagic Events *
Argatroban-treated
Patients
(Study 1 and Study 2)
(n = 568) %
Historical
Control
(n = 193) %
Overall bleeding 5.3 6.7
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 *
Argatroban-treated
Patients
(Study 1 and Study 2)
(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 1 adverse event.
#One patient experienced intracranial hemorrhage 4 days after discontinuation of Argatroban and following therapy with urokinase and oral anticoagulation.
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 HIT/HITTS patients.

Table 4. Non-hemorrhagic Adverse Events in HIT/HITTS Patients *
Argatroban-treated
Patients
(Study 1 and Study 2)
(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 1 adverse event.

Adverse Events Reported in HIT/HITTS Patients Undergoing PCI: The following safety information is based on 91 patients initially treated with Argatroban and 21 patients subsequently re-exposed to Argatroban for a total of 112 PCIs with Argatroban anticoagulation. The adverse events reported in this section include all events regardless of relationship to treatment. Adverse events are separated into hemorrhagic (Table 5) and non-hemorrhagic (Table 6) events.

Major bleeding was defined as bleeding that was overt and associated with a hemoglobin decrease >/=5 g/dL, that led to a transfusion of >/=2 units, or that was intracranial, retroperitoneal, or into a major prosthetic joint.

The rate of major bleeding events and intracranial hemorrhage in the PCI trials was 1.8% and in the placebo arm of the EPILOG trial (placebo plus standard dose, weight-adjusted heparin) was 3.1%.

Table 5. Major and Minor Hemorrhagic Adverse Events in HIT/HITTS Patients Undergoing PCI
Major Hemorrhagic Events *
Argatroban-treated Patients
(n = 112) #
%
Retroperitoneal 0.9
Gastrointestinal 0.9
Intracranial 0
Minor Hemorrhagic Events *
Argatroban-treated Patients
(n = 112) #
%
Groin (bleeding or hematoma) 3.6
Gastrointestinal (includes
hematemesis)
2.6
Genitourinary (includes
hematuria)
1.8
Decrease in hemoglobin and/or
hematocrit
1.8
CABG (coronary arteries) 1.8
Access site 0.9
Hemoptysis 0.9
Other 0.9
*Patients may have experienced more than 1 adverse event.
#91 patients who underwent 112 interventions.
CABG = coronary artery bypass graft.

Table 6 gives an overview of the most frequently observed non-hemorrhagic events (>2%), sorted by decreasing frequency of occurrence among Argatroban-treated PCI patients.

Table 6. Non-hemorrhagic Adverse Events * in HIT/HITTS Patients Undergoing PCI
Argatroban Procedures *
(n = 112) # %
Controls
(n = 2226) & %
Chest pain 15.2 9.3
Hypotension 10.7 10.3
Back pain 8.0 13.7
Nausea 7.1 11.5
Vomiting 6.3 6.8
Headache 5.4 5.5
Bradycardia 4.5 3.5
Abdominal pain 3.6 2.2
Fever 3.6 <0.5
Myocardial infarction 3.6 NR §
*Patients may have experienced more than 1 adverse event.
#91 patients who underwent 112 interventions.
&Controls from EPIC (Evaluation of c7E3 Fab in the Prevention of Ischemic Complications), EPILOG (Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade Study) and CAPTURE (Chimeric 7E3 Antiplatelet Therapy in Unstable angina Refractory to standard treatment) trials. Source: ReoPro® Prescribing Information.
§ NR = not reported.

There were 22 serious adverse events in 17 PCI patients (19.6% in 112 interventions). The types of events, which are listed regardless of relationship to treatment, are shown in Table 7. Table 7 lists the serious adverse events occurring in Argatroban-treated HIT/HITTS patients undergoing PCI.

Table 7. Serious Adverse Events in HIT/HITTS Patients Undergoing PCI *
Coded Term Argatroban Procedures # (n = 112)
Chest pain 1 (0.9%)
Fever 1 (0.9%)
Retroperitoneal hemorrhage 1 (0.9%)
Angina pectoris 2 (1.8%)
Aortic stenosis 1 (0.9%)
Coronary thrombosis 2 (1.8%)
Arterial thrombosis 1 (0.9%)
Myocardial infarction 4 (3.5%)
Myocardial ischemia 2 (1.8%)
Occlusion coronary 2 (1.8%)
Gastrointestinal hemorrhage 1 (0.9%)
Gastrointestinal disorder (GERD) 1 (0.9%)
Cerebrovascular disorder 1 (0.9%)
Lung edema 1 (0.9%)
Vascular disorder 1 (0.9%)
*Individual events may also have been reported elsewhere (see Table 5 and 6).
#91 patients underwent 112 procedures. Some patients may have experienced more than 1 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 various clinical indications (n = 916).

Intracranial Bleeding: 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 PRECAUTIONS, Drug Interactions).

Intracranial bleeding was also observed in a prospective, placebo-controlled study of Argatroban in patients who had onset of acute stroke within 12 hours of study entry. Symptomatic intracranial hemorrhage was reported in 5 of 117 patients (4.3%) who received Argatroban and in none of the 54 patients who received placebo. Asymptomatic intracranial hemorrhage occurred in 5 (4.3%) and 2 (3.7%) of the patients, respectively.

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 various 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/HITTS 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.



REPORTS OF SUSPECTED ARGATROBAN SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Argatroban. The information is not vetted and should not be considered as verified clinical evidence.

Possible Argatroban side effects / adverse reactions in 29 year old male

Reported by a physician from Japan on 2011-10-10

Patient: 29 year old male

Reactions: Activated Partial Thromboplastin Time Prolonged, Cerebral Infarction, Anaemia

Adverse event resulted in: death

Suspect drug(s):
Argatroban
    Dosage: 0.4 mcg/kg/min
    Start date: 2009-11-04
    End date: 2009-11-04

Argatroban
    Dosage: 0.2 mcg/kg/min
    Indication: Heparin-Induced Thrombocytopenia
    Start date: 2009-11-02
    End date: 2009-11-04

Argatroban
    Dosage: 0.2 mcg/kg/min
    Start date: 2009-11-04
    End date: 2009-11-05

Argatroban
    Dosage: 0.2 mcg/kg/min
    Start date: 2009-11-05
    End date: 2009-11-06

Other drugs received by patient: Warfarin Potassium; Heparin Sodium; Warfarin Potassium



Possible Argatroban side effects / adverse reactions in 68 year old male

Reported by a health professional (non-physician/pharmacist) from Japan on 2011-10-21

Patient: 68 year old male

Reactions: Thrombotic Cerebral Infarction, Haemorrhagic Cerebral Infarction

Adverse event resulted in: death

Suspect drug(s):
Edaravone
    Dosage: 30 mg, 2x/day
    Start date: 2011-09-11
    End date: 2011-09-23

Grtpa
    Dosage: 44.7 ml, 1x/day
    Indication: Thrombotic Cerebral Infarction
    Start date: 2011-09-10

Edaravone
    Dosage: 30 mg, 1x/day
    Indication: Thrombotic Cerebral Infarction
    Start date: 2011-09-10
    End date: 2011-09-10

Argatroban
    Dosage: unk
    Indication: Thrombotic Cerebral Infarction
    Start date: 2011-09-12
    End date: 2011-09-17

Plavix
    Dosage: unk
    Administration route: Oral
    Indication: Thrombotic Cerebral Infarction
    Start date: 2011-09-15



Possible Argatroban side effects / adverse reactions in 64 year old female

Reported by a lawyer from United States on 2011-10-26

Patient: 64 year old female weighing 127.0 kg (279.4 pounds)

Reactions: Abdominal Pain, Heparin-Induced Thrombocytopenia, Mental Status Changes, Hyperhidrosis, Erythema, Cardiac Disorder, Haemorrhage Subepidermal, Cardio-Respiratory Arrest, Pharyngeal Oedema, Peroneal Nerve Palsy, Chest Pain, Coagulation Time Prolonged, Diverticular Perforation, Vomiting, Dyspnoea, Nausea, Hypotension, Organ Failure, Anxiety, Abdominal Abscess, Sepsis, Asthenia, Shock

Adverse event resulted in: death

Suspect drug(s):
Argatroban
    Indication: Deep Vein Thrombosis
    Start date: 2008-01-07
    End date: 2008-01-01

Argatroban
    Start date: 2008-02-01
    End date: 2008-02-01

Heparin Sodium Injection
    Indication: Deep Vein Thrombosis
    Start date: 2008-01-02
    End date: 2008-01-02

Heparin Sodium Injection
    Start date: 2008-01-01
    End date: 2008-01-07

Heparin Sodium 5,000 Units IN Dextrose 5%
    Indication: Deep Vein Thrombosis
    Start date: 2008-01-02
    End date: 2008-01-07

Other drugs received by patient: Dilaudid; Lexapro; Nephro-Vite RX; Reglan; Ativan; Ritalin; Vitamin K TAB; Mirtazapine; Septra DS; Warfarin Sodium; Bumex; Probiotica; Atenolol; Prilosec; Aranesp; Cepacol; Zofran



See index of all Argatroban side effect reports >>

Drug label data at the top of this Page last updated: 2006-10-22

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