DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Trasylol (Aprotinin) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Studies of patients undergoing CABG surgery, either primary or repeat, indicate that Trasylol® is generally well tolerated. The adverse events reported are frequent sequelae of cardiac surgery and are not necessarily attributable to Trasylol® therapy. Adverse events reported, up to the time of hospital discharge, from patients in US placebo-controlled trials are listed in the following table. The table lists only those events that were reported in 2% or more of the Trasylol® treated patients without regard to causal relationship.

INCIDENCE RATES OF ADVERSE EVENTS (> = 2%) BY BODY SYSTEM AND TREATMENT FOR ALL PATIENTS FROM US PLACEBO-CONTROLLED CLINICAL TRIALS
Adverse EventAprotinin
(n = 2002)
values in %
Placebo
(n = 1084)
values in %
Any Event7677
Body as a Whole
   Fever1514
   Infection67
   Chest Pain22
   Asthenia22
Cardiovascular
   Atrial Fibrillation2123
   Hypotension810
   Myocardial Infarct66
   Atrial Flutter65
   Ventricular Extrasystoles64
   Tachycardia67
   Ventricular Tachycardia54
   Heart Failure54
   Pericarditis55
   Peripheral Edema55
   Hypertension45
   Arrhythmia43
   Supraventricular Tachycardia43
   Atrial Arrhythmia 33
Digestive
   Nausea119
   Constipation45
   Vomiting34
   Diarrhea32
   Liver Function Tests Abnormal32
Hemic and Lymphatic
   Anemia2 8
Metabolic & Nutritional
   Creatine Phosphokinase Increased21
Musculoskeletal
   Any Event2 3
Nervous
   Confusion44
   Insomnia34
Respiratory
   Lung Disorder8 8
   Pleural Effusion 79
   Atelectasis 56
   Dyspnea4 4
   Pneumothorax44
   Asthma23
   Hypoxia21
Skin and Appendages
   Rash22
Urogenital
   Kidney Function Abnormal3 2
   Urinary Retention3 3
   Urinary Tract Infection2 2

In comparison to the placebo group, no increase in mortality in patients treated with Trasylol® was observed. Additional events of particular interest from controlled US trials with an incidence of less than 2%, are listed below:

EVENTPercentage of patients
treated with Trasylol®
N = 2002
Percentage of patients
treated with Placebo
N = 1084
Thrombosis1.00.6
Shock0.70.4
Cerebrovascular Accident 0.72.1
Thrombophlebitis0.20.5
Deep Thrombophlebitis 0.71.0
Lung Edema1.31.5
Pulmonary Embolus0.30.6
Kidney Failure1.00.6
Acute Kidney Failure0.5 0.6
Kidney Tubular Necrosis0.80.4

Listed below are additional events, from controlled US trials with an incidence between 1 and 2%, and also from uncontrolled, compassionate use trials and spontaneous post-marketing reports. Estimates of frequency cannot be made for spontaneous post-marketing reports (italicized).

Body as a Whole: Sepsis, death, multi-system organ failure, immune system disorder, hemoperitoneum.

Cardiovascular: Ventricular fibrillation, heart arrest, bradycardia, congestive heart failure, hemorrhage, bundle branch block, myocardial ischemia, ventricular tachycardia, heart block, pericardial effusion, ventricular arrhythmia, shock, pulmonary hypertension.

Digestive: Dyspepsia, gastrointestinal hemorrhage, jaundice, hepatic failure.

Hematologic and Lymphatic: Although thrombosis was not reported more frequently in aprotinin versus placebo-treated patients in controlled trials, it has been reported in uncontrolled trials, compassionate use trials, and spontaneous post-marketing reporting. These reports of thrombosis encompass the following terms: thrombosis, occlusion, arterial thrombosis, pulmonary thrombosis, coronary occlusion, embolus, pulmonary embolus, thrombophlebitis, deep thrombophlebitis, cerebrovascular accident, cerebral embolism. Other hematologic events reported include leukocytosis, thrombocytopenia, coagulation disorder (which includes disseminated intravascular coagulation), decreased prothrombin.

Metabolic and Nutritional: Hyperglycemia, hypokalemia, hypervolemia, acidosis.

Musculoskeletal: Arthralgia.

Nervous: Agitation, dizziness, anxiety, convulsion.

Respiratory: Pneumonia, apnea, increased cough, lung edema.

Skin: Skin discoloration.

Urogenital: Oliguria, kidney failure, acute kidney failure, kidney tubular necrosis.

Myocardial Infarction: In the pooled analysis of all patients undergoing CABG surgery, there was no significant difference in the incidence of investigator-reported myocardial infarction (MI) in Trasylol® treated patients as compared to placebo treated patients. However, because no uniform criteria for the diagnosis of myocardial infarction were utilized by investigators, this issue was addressed prospectively in three later studies (two studies evaluated Regimen A, Regimen B and Pump Prime Regimen; one study evaluated only Regimen A), in which data were analyzed by a blinded consultant employing an algorithm for possible, probable or definite MI. Utilizing this method, the incidence of definite myocardial infarction was 5.9% in the aprotinin-treated patients versus 4.7% in the placebo treated patients. This difference in the incidence rates was not statistically significant. Data from these three studies are summarized below.

Incidence of Myocardial Infarctions by Treatment Group Population: All CABG Patients Valid for Safety Analysis
Treatment Definite MI
%
Definite or Probable MI
%
Definite, Probable or Possible MI
%
Pooled Data from Three Studies that Evaluated Regimen A
Trasylol®
Regimen A
n = 646
4.610.7 14.1
Placebo
n = 661
4.711.313.4
Pooled Data from Two Studies that Evaluated Regimen B and Pump Prime Regimen
Trasylol®
Regimen B
n = 241
8.7 15.9 18.7
Trasylol®
Pump Prime
Regimen
n = 239
6.315.7 18.1
Placebo
n = 240
6.315.115.8

Graft Patency: In a recently completed multi-center, multi-national study to determine the effects of Trasylol® Regimen A vs. placebo on saphenous vein graft patency in patients undergoing primary CABG surgery, patients were subjected to routine postoperative angiography. Of the 13 study sites, 10 were in the United States and three were non-U.S. centers (Denmark (1), Israel (2)). The results of this study are summarized below.

Incidence of Graft Closure, Myocardial Infarction and Death by Treatment Group
Overall Closure Rates*Incidence of MI**Incidence of Death***
All Centers
n = 703
%
U.S. Centers
n = 381
%
All Centers
n = 831
%
All Centers
n = 870
%
Trasylol®15.4 9.42.91.4
Placebo 10.99.53.81.6
CI for the
Difference (%)
(Drug - Placebo)
(1.3, 9.6)†(-3.8, 5.9)†-3.3 to 1.5‡-1.9 to 1.4‡
* Population: all patients with assessable saphenous vein grafts
** Population: all patients assessable by blinded consultant
*** All patients
† 90%; per protocol
‡ 95%; not specified in protocol

Although there was a statistically significantly increased risk of graft closure for Trasylol® treated patients compared to patients who received placebo (p=0.035), further analysis showed a significant treatment by site interaction for one of the non-U.S. sites vs. the U.S. centers. When the analysis of graft closures was repeated for U.S. centers only, there was no statistically significant difference in graft closure rates in patients who received Trasylol® vs. placebo. These results are the same whether analyzed as the proportion of patients who experienced at least one graft closure postoperatively or as the proportion of grafts closed. There were no differences between treatment groups in the incidence of myocardial infarction as evaluated by the blinded consultant (2.9% Trasylol® vs. 3.8% placebo) or of death (1.4% Trasylol® vs. 1.6% placebo) in this study.

Hypersensitivity and Anaphylaxis: See CONTRAINDICATIONS and WARNINGS.

Hypersensitivity and anaphylactic reactions during surgery were rarely reported in U.S. controlled clinical studies in patients with no prior exposure to Trasylol® (1/1424 patients or <0.1% on Trasylol® vs. 1/861 patients or 0.1% on placebo). In case of re-exposure the incidence of hypersensitivity/anaphylactic reactions has been reported to reach the 5% level. A review of 387 European patient records involving re-exposure to Trasylol® showed that the incidence of hypersensitivity or anaphylactic reactions was 5.0% for re-exposure within 6 months and 0.9% for re-exposure greater than 6 months.

Laboratory Findings

Serum Creatinine: Trasylol® administration is associated with a risk for renal dysfunction (see WARNINGS: Renal Dysfunction).

Serum Transaminases: Data pooled from all patients undergoing CABG surgery in U.S. placebo-controlled trials showed no evidence of an increase in the incidence of postoperative hepatic dysfunction in patients treated with Trasylol®. The incidence of treatment-emergent increases in ALT (formerly SGPT) > 1.8 times the upper limit of normal was 14% in both the Trasylol® and placebo-treated patients (p=0.687), while the incidence of increases > 3 times the upper limit of normal was 5% in both groups (p=0.847).

Other Laboratory Findings: The incidence of treatment-emergent elevations in plasma glucose, AST (formerly SGOT), LDH, alkaline phosphatase, and CPK-MB was not notably different between Trasylol® and placebo treated patients undergoing CABG surgery. Significant elevations in the partial thromboplastin time (PTT) and celite Activated Clotting Time (celite ACT) are expected in Trasylol® treated patients in the hours after surgery due to circulating concentrations of Trasylol®, which are known to inhibit activation of the intrinsic clotting system by contact with a foreign material (e.g., celite), a method used in these tests (see Laboratory Monitoring of Anticoagulation During Cardiopulmonary Bypass).



REPORTS OF SUSPECTED TRASYLOL SIDE EFFECTS / ADVERSE REACTIONS

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

Possible Trasylol side effects / adverse reactions in 66 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-03

Patient: 66 year old female weighing 85.7 kg (188.6 pounds)

Reactions: Renal Injury, Fear, Pain, Cardiogenic Shock, Stress, Emotional Distress, Anxiety, Death, Multi-Organ Failure, Renal Failure, Renal Impairment, Anhedonia, Injury, Unevaluable Event

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Trasylol

Other drugs received by patient: Metformin HCL; Nipride; Levophed; Toprol-XL; Lidocaine; Midazolam HCL; Primacor; Protamine; Glucotrol; Lisinopril; Aleve (Caplet); Heparin



Possible Trasylol side effects / adverse reactions in 77 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-04

Patient: 77 year old female weighing 60.6 kg (133.4 pounds)

Reactions: Fear of Death, Emotional Distress, Multi-Organ Failure, Anxiety, Renal Failure, Sepsis, Depression, Injury, Nervousness

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Trasylol
    Dosage: 50 ml, q1hr
    Indication: Coronary Artery Bypass
    Start date: 2004-06-17
    End date: 2004-06-17

Trasylol
    Dosage: 1ml test dose
    Indication: Mitral Valve Repair
    Start date: 2004-06-17
    End date: 2004-06-17

Other drugs received by patient: Acetylsalicylic Acid SRT; Plavix; Nortriptyline HCL; Mucomyst; Dobutrex; Pancuronium; Protamine Sulfate; Levothyroxine; Biaxin; Forane; Tiazac; Fentanyl; Cefazolin; Heparin; Toprol-XL; Propofol; RED Blood Cells; Optiray 160; Versed; Primacor; Cardene



Possible Trasylol side effects / adverse reactions in 73 year old male

Reported by a consumer/non-health professional from United States on 2011-10-04

Patient: 73 year old male weighing 127.0 kg (279.4 pounds)

Reactions: Renal Injury, Fear, Pain, Stress, Death, Emotional Distress, Anxiety, Renal Impairment, Anhedonia, Renal Failure, Unevaluable Event, Injury

Adverse event resulted in: death

Suspect drug(s):
Trasylol
    Dosage: initial (test) dose of 1 ml
    Indication: Aortic Valve Replacement
    Start date: 1996-12-11
    End date: 1996-12-11

Trasylol
    Dosage: 100 ml cardiopulmonary bypass prime
    Indication: Coronary Artery Bypass
    Start date: 1996-12-11
    End date: 1996-12-11

Other drugs received by patient: Zocor; RED Blood Cells; Glucophage; Acetylsalicylic Acid SRT; Platelets



See index of all Trasylol side effect reports >>

Drug label data at the top of this Page last updated: 2007-01-09

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2012