Posology : מינונים

2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dose
Bivalirudin Medi-Market 250 mg has been studied only in patients receiving concomitant aspirin.

The recommended dose of bivalirudin Medi-Market 250 mg 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

Bolus Dose
No reduction in the bolus dose is needed for any degree of 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 Medi-Market 250 mg 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.
•   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).

Table 1. Dosing Table

Using 5 mg/mL Concentration
Weight (kg)
Bolus 0.75 mg/kg (mL)           Infusion 1.75 mg/kg/h (mL/h)
43-47                                      7                                  16
48-52                                     7.5                                17.5
53-57                                      8                                  19 58-62                                      9                                  21 63-67                                     10                                  23 68-72                                    10.5                                24.5 73-77                                     11                                  26 78-82                                     12                                  28 83-87                                     13                                  30 88-92                                    13.5                                31.5 93-97                                     14                                  33 98-102                                    15                                  35 103-107                                    16                                  37 108-112                                   16.5                                38.5 113-117                                    17                                  40 118-122                                    18                                  42 123-127                                    19                                  44 128-132                                   19.5                                45.5 133-137                                    20                                  47 138-142                                    21                                  49 143-147                                    22                                  51 148-152                                   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 Medi-Market 250 mg.
Table 2. Drugs Not for Administration in the Same Intravenous Line with Bivalirudin Medi-Market 250 mg

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 Medi-Market 250 mg containing particulate matter should not be used. Reconstituted material will be a clear and colorless solution.

2.4 Storage After Reconstitution
Do not freeze reconstituted or diluted bivalirudin Medi-Market 250 mg. Chemical and physical in-use stability of the reconstituted material has been demonstrated at 2° to 8°C for up to 24 hours. Diluted bivalirudin Medi-Market 250 mg with a concentration of 0.5 mg/mL or 5 mg/mL is chemically and physically stable at 25°C for up to 24 hours. Discard any unused portion of reconstituted solution remaining in the vial.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C - 8°C unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Please also refer to section 16.3.