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Argatroban (Argatroban) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse reaction is also discussed in other sections of the labeling: Risk of Hemorrhage [see Warnings and Precautions ].

Adverse Events in Patients with HIT (With or Without Thrombosis)

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. 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 4 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 with HIT (with or without thrombosis).

Table 4.
Major and Minor Hemorrhagic Adverse Events in Patients With HIT*

Major Hemorrhagic Eventsa

      

Argatroban-treated Patients
(Study 1 and Study 2)
(n = 568) % 

Historical
Controlc
(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

0b

0.5

Minor Hemorrhagic Eventsa

              

Argatroban-treated Patients
(Study 1 and Study 2)

(n = 568)  % 

Historical Controlc
(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

*  with or without thrombosis
a)  Patients may have experienced more than 1 adverse event.
b)  One patient experienced intracranial hemorrhage 4 days after discontinuation of argatroban and following therapy with urokinase and
oral anticoagulation.
c)  The historical control group consisted of patients with a clinical diagnosis of HIT (with or without thrombosis) that were considered eligible by an independent medical panel.
        DIC = disseminated intravascular coagulation.
        BKA = below the knee amputation.

Table 5 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 5.
Non-hemorrhagic Adverse Events in Patientsa With HITb

          

Argatroban-treated Patients
(Study 1 and Study 2)
(n = 568) % 

Historical
Controlc
(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

a) Patients may have experienced more than 1 adverse event.
b) with or without thrombosis
c) The historical control group consisted of patients with a clinical diagnosis of HIT (with or without thrombosis) that were considered eligible by an independent medical panel.

Adverse Events in Patients with or at Risk for HIT 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. Adverse events are separated into hemorrhagic (Table 6) and non-hemorrhagic (Table 7) 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 in patients treated with argatroban in the PCI trials was 1.8%.

Table 6.
Major and Minor Hemorrhagic Adverse Events in Patients With HIT Undergoing PCI

Major Hemorrhagic Eventsa

          

Argatroban-treated
Patients
(n = 112)b % 

Retroperitoneal

0.9

Gastrointestinal

0.9

Intracranial

0

Minor Hemorrhagic Eventsa

            

Argatroban-treated
Patients
(n = 112)b  % 

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

a)  Patients may have experienced more than 1 adverse event.
b)  91 patients who underwent 112 interventions.
     CABG = coronary artery bypass graft.

Table 7 gives an overview of the most frequently observed non-hemorrhagic events (>2%), sorted by decreasing frequency of occurrence among argatroban-treated PCI patients.

Table 7.
Non-hemorrhagic Adverse Eventsa in Patients With HIT Undergoing PCI

          

Argatroban Proceduresa
(n = 112)b  %

 

Chest pain

15.2

Hypotension

10.7

Back pain

8.0

Nausea

7.1

Vomiting

6.3

Headache

5.4

Bradycardia

4.5

Abdominal pain

3.6

Fever

3.6

Myocardial infarction

3.6

a)  Patients may have experienced more than 1 adverse event.
b)  91 patients who underwent 112 interventions.

There were 22 serious adverse events in 17 PCI patients (19.6% in 112 interventions). Table 8 lists the serious adverse events occurring in argatroban-treated patients with or at risk for HIT undergoing PCI.

Table 8.
Serious Adverse Events in Patients With HIT Undergoing PCIa

Coded Term

Argatroban Proceduresb
(n = 112)

Myocardial infarction

4 (3.5%)

Angina pectoris

2 (1.8%)

Coronary thrombosis

2 (1.8%)

Myocardial ischemia

2 (1.8%)

Occlusion coronary

2 (1.8%)

Chest pain

1 (0.9%)

Fever

1 (0.9%)

Retroperitoneal hemorrhage

1 (0.9%)

Aortic stenosis

1 (0.9%)

Arterial thrombosis

1 (0.9%)

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%)

a)  Individual events may also have been reported elsewhere (see Table 6 and 7).
b)  91 patients underwent 112 procedures. Some patients may have experienced more than 1 event.

Intracranial Bleeding in Other Populations

Increased risks for intracranial bleeding have been observed in investigational studies of argatroban for other uses.  In a study of patients with acute myocardial infarction receiving both argatroban and thrombolytic therapy (streptokinase or tissue plaminogen activator), the overall frequency of intracranial bleeding was 1% (8 out of 810 patients).  Intracranial bleeding was not observed in 317 subjects or patients who did not receive concomitant thrombolysis [see Drug Interactions ].

The safety and effectiveness of argatroban for cardiac indications other than PCI in patients with HIT have not been established.  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 at 1 to 3 mcg/kg/min 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

One hundred fifty-six 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) or contrast media.

Allergic reactions or suspected allergic reactions in populations other than patients with HIT (with or without thrombosis) 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%

Limited data are available on the potential formation of drug-related antibodies. Plasma from 12 healthy volunteers treated with argatroban over 6 days showed no evidence of neutralizing antibodies. No loss of anticoagulant activity was noted with repeated administration of argatroban to more than 40 patients.



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: 2014-03-31

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