administration in a study of human volunteers, with detectable plasma levels measured up to 6 h post-injection. Following sc injection of 0.3 mg/kg, the aPTT was prolonged to 150 ± 19.4% of the baseline value, and after a 1 mg/kg sc dose, to 176 ± 19.4% of the baseline value; the corresponding INR values increased to 1.18 ± 0.05 and to 1.48 ± 0.17 (Fox et al., 1993). Urinary excretion of the drug was complete by 8-12 h. To date, there are no good efficacy data using the sc route of administration.

A number of drugs commonly used in patients undergoing PCI have been tested for Y-site compatibility with bivalirudin. Testing was for short-term mixing, rather than longer-term interactions (4 h). Drugs found to be compatible with bivalirudin included abciximab, dexamethasone, digoxin, diphenhydramine, dopa-mine, epinephrine, eptifibatide, esmolol, furosemide, heparin, lidocaine, morphine, nitroglycerin, potassium chloride, sodium bicarbonate, tirofiban, and verapamil (The Medicines Company, 2005; Reed and Bell, 2002). Dobutamine was compatible at concentrations up to 4mg/mL but incompatible at a concentration of 12.5 mg/ mL (Trissel and Saenz, 2002; Hartman et al., 2004).

Trissel and Saenz (2002) looked at the compatibility of bivalirudin with 96 selected drugs including anti-infectives, analgesics, antihistamines, diuretics, steroids, and other supportive care agents by visual observation, turbidity measurement, and electronic particle content assessment. Eighty-seven were compatible with a bivalirudin dilution. Table 2 lists the nine drugs found by Reed and Bell (2002) and Trissel and Saenz to cause haze formation or gross precipitation, and which thus should not be administered in the same line as bivalirudin.

Drug-drug interaction studies have been performed with the thienopyridine derivative ticlopidine, the GPIIb/IIIa inhibitors abciximab, eptifibatide and tirofiban, and low molecular weight heparin (LMWH) and UFH (Reed and Bell, 2002). No pharmacodynamic interactions occurred between bivalirudin and these agents.

TABLE 2 Drugs Incompatible with Bivalirudin Alteplase

Amiodarone hydrochloride Amphotericin B Chlorpromazine hydrochloride Diazepam

Prochlorperazine edisylate Reteplase Streptokinase Vancomycin hydrochloride

Source: Reed and Bell, 2002; The Medicines Company, 2005.

In patients undergoing PTCA/PCI, coadministration of bivalirudin in conjunction with heparin, warfarin, thrombolytic therapy, or GPIIb/IIIa inhibitors has been associated with increased risk of bleeding compared to patients not receiving these concomitant medications (The Medicines Company, 2005). Aspirin was associated with a mild increase in bleeding times in patients receiving bivalirudin infusions when compared to placebo. These changes were not felt to be clinically significant (Fox et al., 1993).

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