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 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.

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

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.

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%

REPORTS OF SUSPECTED ARGATROBAN SIDE EFFECTS / ADVERSE REACTIONS

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