ANGIOMAX- bivalirudin injection, powder, lyophilized, for solution
The Medicines Company
Angiomax contains bivalirudin which is specific and reversible direct thrombin inhibitor. Bivalirudin is synthetic, 20 amino acid peptide, with the chemical name of D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycyl-glycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine. The active pharmaceutical ingredient is in the form of bivalirudin trifluoroacetate as white to off-white powder. The chemical name for bivalirudin trifluoroacetate is D-phenylalanyl-L-prolyl-L-arginyl-L-prolyl-glycyl-glycyl-glycyl-glycyl-L-asparagyl-glycyl-L-aspartyl-L-phenylalanyl-L-glutamyl-L-glutamyl-L-isoleucyl-L-prolyl-L-glutamyl-L-glutamyl-L-tyrosyl-L-leucine trifluoroacetate.he molecular weight of bivalirudin is 2180 daltons (anhydrous free base peptide).
Angiomax is supplied as sterile white lyophilized cake, in single-dose vials. Each vial contains 250 mg bivalirudin, equivalent to an average of 275 mg of bivalirudin trifluoroactetate*, 125 mg mannitol, and sodium hydroxide to adjust the pH to 5-6 (equivalent of approximately 12.5 mg sodium). When reconstituted with Sterile Water for Injection, the product yields clear to opalescent, colorless to slightly yellow solution, pH 5-6.
*The range of bivalirudin trifluoroacetate is 270 mg to 280 mg based on range of trifluoroacetic acid composition of 1.7 to 2.6 equivalents.
Mechanism of Action
Bivalirudin directly inhibits thrombin by specifically binding both to the catalytic site and to the anion-binding exosite of circulating and clot-bound thrombin. Thrombin is serine proteinase that plays central role in the thrombotic process, acting to cleave fibrinogen into fibrin monomers and to activate Factor XIII to Factor XIIIa, allowing fibrin to develop covalently cross-linked framework which stabilizes the thrombus; thrombin also activates Factors and VIII, promoting further thrombin generation, and activates platelets, stimulating aggregation and granule release. The binding of bivalirudin to thrombin is reversible as thrombin slowly cleaves the bivalirudin-Arg3-Pro4 bond, resulting in recovery of thrombin active site functions
PATIENT COUNSELING info.
Advise patients to watch carefully for any signs of bleeding or bruising and to report these to their health care provider when they occur.
Advise patients to discuss with their health care provider their use of any other medications, including over-the-counter medications or herbal products, prior to Angiomax use. Examples of other medications that should not be taken with Angiomax are warfarin and heparin.
INDICATIONS AND USAGE
1.1 Percutaneous Transluminal Coronary Angioplasty (PTCA)
Angiomax? (bivalirudin) is indicated for use as an anticoagulant in patients with unstable angina undergoing percutaneous transluminal coronary angioplasty (PTCA).
1.2 Percutaneous Coronary Intervention (PCI)
Angiomax with provisional use of glycoprotein IIb/IIIa inhibitor (GPI) as listed in the REPLACE-2 trial [see Clinical Studies ] is indicated for use as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI).
Angiomax is indicated for patients with, or at risk of, heparin induced thrombocytopenia (HIT) or heparin induced thrombocytopenia and thrombosis syndrome (HITTS) undergoing PCI.
1.3 Use with Aspirin
Angiomax in these indications is intended for use with aspirin and has been studied only in patients receiving concomitant aspirin.
DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
Angiomax is for intravenous administration only.
Angiomax is intended for use with aspirin (300-325 mg daily) and has been studied only in patients receiving concomitant aspirin.
GPI administration should be considered in the event that any of the conditions listed in the REPLACE-2 clinical trial description [see Clinical Studies ] is present.
For patients who have HIT/HITTS
The recommended dose of Angiomax in patients with HIT/HITTS undergoing PCI is an IV bolus of 0.75 mg/kg. This should be followed by continuous infusion at rate of 1.75 mg/kg/h for the duration of the procedure.
For ongoing treatment post procedure
? Angiomax infusion may be continued following PCI/PTCA for up to hours post-procedure at the discretion of the treating physician.
? In patients with ST segment elevation myocardial infarction (STEMI) continuation of the Angiomax infusion at rate of 1.75 mg/kg/h following PCI/PTCA for up to hours post-procedure should be considered to mitigate risk of stent thrombosis.
After four hours, an additional IV infusion of Angiomax may be initiated at rate of 0.2 mg/kg/h (low-rate infusion), for up to 20 hours, if needed.
Storage after Reconstitution
Do not freeze reconstituted or diluted Angiomax. Reconstituted material may be stored at 2-8?C for up to 24 hours. Diluted Angiomax with concentration of between 0.5 mg/mL and mg/mL is stable at room temperature for up to 24 hours. Discard any unused portion of reconstituted solution remaining in the vial.
3 DOSAGE FORMS AND STRENGTHS
For injection: 250 mg of bivalirudin in single-dose vial for reconstitution. Each vial contains 250 mg of bivalirudin equivalent to an average of 275 mg bivalirudin trifluoroacetate*. Following reconstitution with Sterile Water for Injection, the product is clear to opalescent, colorless to slightly yellow solution, pH 5-6.
*The range of bivalirudin trifluoroacetate is 270 to 280 mg based on range of trifluoroacetic acid composition of 1.7 to 2.6 equivalents.
Angiomax is contraindicated in patients with:
Active major bleeding;
Hypersensitivity (e.g., anaphylaxis) to Angiomax or its components