Angiomax Side Effects, and Drug Interactions - Bivalirudin

Angiomax Side Effects, and Drug Interactions - Bivalirudin

SIDE EFFECTS

In 4312 patients undergoing PTCA for treatment of unstable angina in 2 randomized, double-blind studies comparing Angiomax to heparin, Angiomax patients exhibited lower rates of major bleeding and lower requirements for blood transfusions. The incidence of major bleeding is presented in Table 3. The incidence of major bleeding was lower in the Angiomax group than in the heparin group.

In the 2 randomized double-blind clinical trials of Angiomax in patients undergoing PTCA, 82% of 2161 Angiomax-treated patients and 83% of 2151 heparin-treated patients experienced at least one treatment-emergent adverse event. The most frequent treatment-emergent events were back pain (42%), pain (15%), nausea (15%), headache (12%), and hypotension (12%) in the Angiomax-treated group. Treatment-emergent adverse events other than bleeding reported for ³5% of patients in either treatment group are shown in Table 4.

Serious, non-bleeding adverse events were experienced in 2% of 2161 Angiomax-treated patients and 2% of 2151 heparin-treated patients. The following individual serious non-bleeding adverse events were rare (>0.1% to <1%) and similar in incidence between Angiomax- and heparin-treated patients. These events are listed by body system: Body as a Whole: fever, infection, sepsis; Cardiovascular: hypotension, syncope, vascular anomaly, ventricular fibrillation; Nervous: cerebral ischemia, confusion, facial paralysis; Respiratory: lung edema; Urogenital: kidney failure, oliguria.

There have been reports of thrombus formation with the use of Angiomax during percutaneous coronary intervention (PCI), including intracoronary brachytherapy. Fatal outcomes have been reported.

Bivalirudin does not exhibit binding to plasma proteins (other than thrombin) or red blood cells.

Drug-drug interaction studies have been conducted with the adenosine diphosphate (ADP) antagonist, ticlopidine, and the glycoprotein IIb/IIIa inhibitor, abciximab, and with low molecular weight heparin. Although data are limited, precluding conclusions regarding efficacy and safety in combination with these agents, the results do not suggest pharmacodynamic interactions. In patients treated with low molecular weight heparin, low molecular weight heparin was discontinued at least 8 hours prior to the procedure and administration of Angiomax.

The safety and effectiveness of Angiomax have not been established when used in conjunction with platelet inhibitors other than aspirin, such as glycoprotein IIb/IIIa inhibitors.

In clinical trials in patients undergoing PTCA, co-administration of Angiomax with heparin, warfarin or thrombolyt-ics was associated with increased risks of major bleeding events compared to patients not receiving these concomitant medications. There is no experience with co-administration of Angiomax and plasma expanders such as dextran. Angiomax should be used with caution in patients with disease states associated with an increased risk of bleeding.

Among 494 subjects who received Angiomax in clinical trials and were tested for antibodies, 2 subjects had treatment-emergent positive bivalirudin antibody tests. Neither subject demonstrated clinical evidence of allergic or ana-phylactic reactions and repeat testing was not performed. Nine additional patients who had initial positive tests were negative on repeat testing.