ACOVA SIDE EFFECTS
- Generic Name: argatroban
- Brand Name: Acova
- Drug Class: Anticoagulants, Cardiovascular, Thrombin Inhibitors
SIDE EFFECTS
Adverse Events Reported In HIT/HITTS Patients
The following safety information is based on all 568 patients treated with ACOVA™ 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 1 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 1: 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 hemoglobin/ 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 2 gives an overview of the most frequently observed non-hemorrhagic events sorted by decreasing frequency of occurrence (≥2%) among argatroban-treated patients.
Table 2: 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 1127 individuals who were treated with ACOVA™ 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 ACOVA™ and thrombolytic therapy with streptokinase. The overall frequency of this potentially life-threatening complication among patients receiving both ACOVA™ 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 ACOVA™ 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
SRC: NLM .