1. Name of the medicinal product
Angiox 250 mg powder for concentrate for solution for injection or infusion.
2. Qualitative and quantitative composition
Each vial contains 250 mg bivalirudin.
After reconstitution 1 ml contains 50 mg bivalirudin.
After dilution 1 ml contains 5 mg bivalirudin.
For the full list of excipients see section 6.1.
3. Pharmaceutical form
Powder for concentrate for solution for injection or infusion (powder for concentrate).
White to off-white lyophilised powder.
4. Clinical particulars
4.1 Therapeutic indications
Angiox is indicated as an anticoagulant in adult patients undergoing percutaneous coronary intervention (PCI), including patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.
Angiox is also indicated for the treatment of adult patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) planned for urgent or early intervention.
Angiox should be administered with aspirin and clopidogrel.
4.2 Posology and method of administration
Angiox should be administered by a physician experienced in either acute coronary care or in coronary intervention procedures.
Posology
Patients undergoing PCI, including primary PCI
The recommended dose of Angiox for patients undergoing PCI is an intravenous bolus of 0.75 mg/kg body weight followed immediately by an intravenous infusion at a rate of 1.75 mg/kg body weight/hour for at least the duration of the procedure. The infusion may be continued for up to 4 hours post-PCI as clinically warranted. After cessation of the 1.75 mg/kg /h infusion, a reduced infusion dose of 0.25 mg/kg/h may be continued for 4 – 12 hours as clinically necessary.
Patients should be carefully monitored following primary PCI for signs and symptoms consistent with myocardial ischaemia.
Patients with unstable angina/non-ST segment elevated myocardial infarction (UA/NSTEMI)
The recommended starting dose of Angiox for patients with ACS is an intravenous bolus of 0.1 mg/kg followed by an infusion of 0.25 mg/kg/h. Patients who are to be medically managed may continue the infusion of 0.25 mg/kg/h for up to 72 hours.
If the patient proceeds to PCI, an additional bolus of 0.5 mg/kg of bivalirudin should be administered before the procedure and the infusion increased to 1.75 mg/kg/h for the duration of the procedure.
Following PCI, the reduced infusion dose of 0.25 mg/kg/h may be resumed for 4 to 12 hours as clinically necessary.
For patients who proceed to coronary artery bypass graft (CABG) surgery off pump, the intravenous (IV) infusion of bivalirudin should be continued until the time of surgery. Just prior to surgery, a 0.5 mg/kg bolus dose should be administered followed by a 1.75 mg/kg/h infusion for the duration of the surgery.
For patients who proceed to CABG surgery on pump, the IV infusion of bivalirudin should be continued until 1 hour prior to surgery after which the infusion should be discontinued and the patient treated with unfractionated heparin (UFH).
To ensure appropriate administration of bivalirudin, the completely dissolved, reconstituted and diluted product should be thoroughly mixed prior to administration (see section 6.6). The bolus dose should be administered by a rapid intravenous push to ensure that the entire bolus reaches the patient before the start of the procedure.
Intravenous infusion lines should be primed with bivalirudin to ensure continuity of drug infusion after delivery of the bolus.
The infusion dose should be initiated immediately after the bolus dose is administered, ensuring delivery to the patient prior to the procedure, and continued uninterrupted for the duration of the procedure. The safety and efficacy of a bolus dose of Angiox without the subsequent infusion has not been eva luated and is not recommended even if a short PCI procedure is planned.
An increase in the activated clotting time (ACT) may be used as an indication that a patient has received Angiox.
ACT values 5 minutes after bivalirudin bolus average 365 +/- 100 seconds. If the 5-minute ACT is less than 225 seconds, a second bolus dose of 0.3 mg/kg should be administered.
Once the ACT value is greater than 225 seconds, no further monitoring is required provided the 1.75 mg/kg/h infusion