2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
Bivalirudin has been studied only in patients receiving concomitant aspirin.
The recommended dose of bivalirudin is an intravenous bolus dose of 0.75 mg/kg, followed immediately by an infusion of 1.75 mg/kg/h for the duration of the procedure. Five minutes after the bolus dose has been administered, an activated clotting time (ACT) should be performed and an additional bolus of 0.3 mg/kg should be given if needed.
Extended duration of infusion following PCI at 1.75 mg/kg/h for up to 4 hours post-procedure should be considered in patients with ST segment elevation MI (STEMI).
2.2 Dose Adjustment in Renal Impairment
Maintenance Infusion
In patients with creatinine clearance less than 30 mL/min (by Cockcroft Gault equation), reduce the infusion rate to 1 mg/kg/h. Monitor anticoagulant status in patients with renal impairment.
In patients on hemodialysis, reduce the infusion rate to 0.25 mg/kg/h [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
2.3 Instructions for Preparation and Administration
Bivalirudin is intended for intravenous bolus injection and continuous infusion after reconstitution and dilution.
Preparation Instructions for Bolus Injection and Continuous Infusion
- To each 250 mg vial, add 5 mL of Sterile Water for Injection, USP.
- Gently swirl until all material is dissolved.
- Withdraw and discard 5 mL from a 50 mL infusion bag containing 5% Dextrose in Water or 0.9% Sodium Chloride for Injection.
- Add the contents of the reconstituted vial to the infusion bag containing 5% Dextrose in Water or 0.9% Sodium Chloride for Injection to yield a final concentration of 5 mg/mL (e.g., 1 vial in 50 mL; 2 vials in 100 mL; 5 vials in 250 mL).
- Adjust the dose to be administered according to the patient's weight (see Table 1).
| Weight (kg) | Using 5 mg/mL Concentration | |
|---|---|---|
| Bolus 0.75 mg/kg (mL) | Infusion 1.75 mg/kg/h (mL/h) | |
| 43 to 47 | 7 | 16 |
| 48 to 52 | 7.5 | 17.5 |
| 53 to 57 | 8 | 19 |
| 58 to 62 | 9 | 21 |
| 63 to 67 | 10 | 23 |
| 68 to 72 | 10.5 | 24.5 |
| 73 to 77 | 11 | 26 |
| 78 to 82 | 12 | 28 |
| 83 to 87 | 13 | 30 |
| 88 to 92 | 13.5 | 31.5 |
| 93 to 97 | 14 | 33 |
| 98 to 102 | 15 | 35 |
| 103 to 107 | 16 | 37 |
| 108 to 112 | 16.5 | 38.5 |
| 113 to 117 | 17 | 40 |
| 118 to 122 | 18 | 42 |
| 123 to 127 | 19 | 44 |
| 128 to 132 | 19.5 | 45.5 |
| 133 to 137 | 20 | 47 |
| 138 to 142 | 21 | 49 |
| 143 to 147 | 22 | 51 |
| 148 to 152 | 22.5 | 52.5 |
Drug Compatibilities
No incompatibilities have been observed with administration sets.
Do not administer the drugs listed in Table 2 in the same intravenous line with bivalirudin.
| Alteplase |
| Amiodarone HCl |
| Amphotericin B |
| Chlorpromazine HCl |
| Diazepam |
| Dobutamine |
| Prochlorperazine Edisylate |
| Reteplase |
| Streptokinase |
| Vancomycin HCl |
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Preparations of bivalirudin containing particulate matter should not be used. Reconstituted material will be a clear to slightly opalescent, colorless to slightly yellow solution.
2.4 Storage after Reconstitution
Do not freeze reconstituted or diluted bivalirudin. Reconstituted material may be stored at 2 to 8°C for up to 24 hours. Diluted bivalirudin with a concentration of between 0.5 mg/mL and 5 mg/mL is stable at room temperature for up to 24 hours. Discard any unused portion of reconstituted solution remaining in the vial.