Angiox

Angiox should be administered by a physician experienced in either acute coronary care or in coronary intervention procedures. 75 mg/kg body weight/hour for at least the duration of the procedure. 25 mg/kg body weight/hour for an additional 4 – 12 hours as clinically necessary.

4). 25 mg/kg/h. 25 mg/kg/h for up to 72 hours. 75 mg/kg/h for the duration of the procedure. 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 infusion of bivalirudin should be continued until the time of surgery.

75 mg/kg/h intravenous infusion for the duration of the surgery. For patients who proceed to CABG surgery on pump, the intravenous 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).

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 bivalirudin without the subsequent infusion has not been evaluated 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 bivalirudin. ACT values 5 minutes after bivalirudin bolus average 365 +/- 100 seconds. 3 mg/kg should be administered. 75 mg/kg/h infusion dose is properly administered.

Where insufficient ACT increase is observed, the possibility of medication error should be considered, for example inadequate mixing of Angiox or intravenous equipment failures. The arterial sheath can be removed 2 hours after discontinuation of the bivalirudin infusion without anticoagulation monitoring.

1). Patients can be started on Angiox 30 minutes after discontinuation of unfractionated heparin given intravenously, or 8 hours after discontinuation of low molecular weight heparin given subcutaneously. Angiox can be used in conjunction with a GP IIb/IIIa inhibitor.

Summary of the safety profile  The most frequent serious and fatal adverse reactions are major haemorrhage (access site and non access-site bleeding, including intracranial haemorrhage) and hypersensitivity, including anaphylactic shock.

Coronary artery thrombosis and coronary stent thrombosis with myocardial infarction, and catheter thrombosis have each been reported rarely. Administration errors may lead to fatal thrombosis. Medicinal product no longer authorised 7 Tabulated list of adverse reactions Adverse reactions for bivalirudin from HORIZONS, ACUITY, REPLACE-2 trials and post-marketing experience are listed by system organ class in Table 1.

Table 1. Adverse reactions for bivalirudin from HORIZONS, ACUITY, REPLACE-2 trials and post-marketing experience System organ class Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare ( <1/10,000) Blood and lymphatic system disorders Haemoglobin decreased Thrombocytopenia Anaemia Immune system disorders Hypersensitivity, including anaphylactic reaction and shock, including reports with fatal outcome Nervous system disorders Headache Intracranial haemorrhage Eye disorders Intraocular haemorrhage Ear and labyrinth disorders Ear haemorrhage Cardiac disorders Cardiac tamponade, Pericardial haemorrhage, Myocardial infarction, Coronary artery thrombosis, Bradycardia, Ventricular tachycardia’ Angina pectoris, Chest pain Vascular disorders Minor haemorrha ge at any site Major haemorrhage at any site including reports with fatal outcome Haematoma, Hypotension Coronary stent thrombosis including reports with fatal outcomec Thrombosis including reports with fatal outcome, Arteriovenous fistula, Catheter thrombosis, Vascular pseudoaneurysm Compartment syndromea, bMedicinal product no longer authorised 8 System organ class Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare ( <1/10,000) Respiratory, thoracic and mediastinal disorders Epistaxis, Haemoptysis, Pharyngeal haemorrhage Pulmonary haemorrhage Dyspnoeaa Gastrointestinal disorders Gastrointestinal haemorrhage (including haematemesis, melaena, oesophageal haemorrhage, anal haemorrhage), Retroperitoneal haemorrhage, Gingival haemorrhage, Nausea Peritoneal haemorrhage, Retroperitoneal haematoma, Vomiting Skin and subcutaneous tissue disorders Ecchymosis Rash, Urticaria Musculoskeletal and connective tissue disorders Back pain, Groin pain Renal and urinary disorders Haematuria General disorders and administration site conditions Access site haemorrhage, Vessel puncture site haematoma >5 cm, Vessel puncture site haematoma <5 cm Injection site reactions (Injection site discomfort, Injection site pain, Puncture site reaction) Investigations INR increasedd Injury, poisoning and procedural complications Reperfusion injury (no or slow reflow), Contusion a.

Angiox is not intended for intramuscular use. Do not administer intramuscularly. 5). Although most bleeding associated with bivalirudin occurs at the site of arterial puncture in patients undergoing PCI, haemorrhage can occur at any site during therapy.

Unexplained decreases in haematocrit, haemoglobin or blood pressure may indicate haemorrhage. Treatment should be stopped if bleeding is observed or suspected. There is no known antidote to bivalirudin but its effect wears off quickly (T½ is 25 ± 12 minutes).

2). 5). When bivalirudin is combined with a platelet inhibitor or an anti-coagulant medicine, clinical and biological parameters of haemostasis should be regularly monitored. In patients taking warfarin who are treated with bivalirudin, International Normalised Ratio (INR) monitoring should be considered to ensure that it returns to pre-treatment levels following discontinuation of bivalirudin treatment.

Hypersensitivity Allergic type hypersensitivity reactions were reported uncommonly (≥1/1,000 to ≤1/100) in clinical trials. Necessary preparations should be made to deal with this. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of chest, wheezing, hypotension and anaphylaxis.

In the case of shock, the current medical standards for shock treatment should be applied. 8). Treatment-emergent positive bivalirudin antibodies are rare and have not been associated with clinical evidence of allergic or anaphylactic reactions.

Caution should be exercised in patients previously treated with lepirudin who had developed lepirudin antibodies. 1). The majority of these cases were non-fatal. 2). Medicinal product no longer authorised 6 Brachytherapy Intra-procedural thrombus formation has been observed during gamma brachytherapy procedures with Angiox.

Angiox should be used with caution during beta brachytherapy procedures. e. essentially “sodium-free”.

1, or to hirudins  active bleeding or increased risk of bleeding because of haemostasis disorders and/or irreversible coagulation disorders  severe uncontrolled hypertensionMedicinal product no longer authorised 5  subacute bacterial endocarditis  severe renal impairment (GFR<30 ml/min) and in dialysis-dependent patients