Abciximab

It is also not known whether abciximab can cause foetal harm when administered to a pregnant woman. ReoPro should not be used during pregnancy unless clearly necessary.

Breast-feeding of infants should be discontinued in breast-feeding mothers, since the secretion of abciximab in animal or human breast milk has not been studied.

Fertility

Animal reproduction studies have not been conducted with abciximab. It is also not known whether abciximab can affect reproduction capacity.

Not relevant.

Summary of the safety profile

The most frequent adverse reactions are bleeding, back pain, hypotension, nausea, chest pain, vomiting, headache, bradycardia, fever (pyrexia), puncture site pain and thrombocytopenia. Cardiac tamponade, pulmonary (mostly alveolar) haemorrhage and adult respiratory distress syndrome have been reported rarely.

List of adverse reactions

The adverse reactions listed below are based on experience from clinical studies and from world-wide post-marketing use of abciximab. Within the organ system classes, adverse reactions are listed under headings of frequency using the following convention: 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); Not known (cannot be estimated from the available data).

List of ADRs:

Blood and lymphatic system disorders

Common: Thrombocytopenia

Immune system disorders

Rare: Anaphylactic reaction, hypersensitivity/allergic reactions

Nervous system disorders

Common: Headache

Cardiac disorders

Common: Bradycardia

Rare: Cardiac tamponade

Vascular disorders

Common: Bleeding, hypotension, peripheral oedema

Uncommon: Intracranial haemorrhage

Rare: Fatal bleeding

Respiratory, thoracic and mediastinal disorders

Rare: Adult respiratory distress syndrome, pulmonary haemorrhage

Gastrointestinal disorders

Common: Gastrointestinal haemorrhage, nausea, vomiting

Musculoskeletal and connective tissue disorders

Common: Back pain

General disorders and administration site conditions

Common: Chest pain, pyrexia, puncture site pain, abdominal pain

Description of selected adverse reactions

Bleeding

In the EPIC study, in which a non-weight-adjusted, standard heparin dose regimen was used, the most common complication during ReoPro therapy was bleeding during the first 36 hours. The incidences of major bleeding, minor bleeding and transfusion of blood products were approximately doubled. In patients who had major bleeding, 67% had bleeding associated with the arterial access site in the groin.

Major and minor bleeding are defined as follows:

Major bleeding: Decrease in haemoglobin >5 g/dL

Minor bleeding: Spontaneous gross haematuria or haematemesis, or observed blood loss with a haemoglobin decrease >3 g/dL, or a decrease in haemoglobin ≥4 g/dL with no observed blood loss.

In a subsequent clinical study, EPILOG, using the heparin regimen, sheath removal and femoral access care guidelines outlined in section 4.4, paragraph on Bleeding precautions, the incidence of major bleeding not associated with CABG surgery in patients treated with ReoPro (1.1%) was not different from patients receiving placebo (1.1%) and there was no significant increase in the incidence of intracranial haemorrhage. The reduction in major bleeding observed in the EPILOG study was achieved without loss of efficacy. Likewise, in the EPISTENT study, the incidence of major bleeding not associated with CABG surgery in patients receiving ReoPro plus balloon angioplasty (0.6%) or ReoPro with stent placement (0.8%) was not significantly different from patients receiving placebo with stent placement (1.0%). In the CAPTURE study, which did not use the low-dose heparin regimen, the incidence of major bleeding not associated with CABG surgery was higher in patients receiving ReoPro (3.8%) than in patients receiving placebo (1.9%).

Although data are limited, ReoPro treatment was not associated with excess major bleeding in patients who underwent CABG surgery. Some patients with prolonged bleeding times received platelet transfusions to correct the bleeding time prior to surgery.

Other vascular disorders

Clinical studies suggest that adherence to the currently recommended, weight adjusted heparin regimen is associated with a lower risk of intracranial haemorrhage than previous (higher dose, non-weight-adjusted) protocols. The total incidence of intracranial haemorrhage and non-haemorrhagic stroke in all 4 pivotal studies was similar, 9/3023 (0.30%) for placebo patients and 15/4680 (0.32%) for ReoPro treated patients. The incidence of intracranial haemorrhage was 0.10% in placebo patients and 0.15% in ReoPro patients.

The GUSTO V study randomised 16,588 patients with acute myocardial infarction to treatment with combined ReoPro and half-dose reteplase or full dose reteplase alone. The incidence of moderate or severe non-intracranial bleeding was increased in those patients receiving ReoPro and half-dose reteplase versus those receiving reteplase alone (4.6% versus 2.3% respectively).

Thrombocytopenia

Patients treated with ReoPro were more likely to experience thrombocytopenia (platelet counts less than 100,000 cells/μL) than placebo patients. The incidence in the EPILOG and EPISTENT studies using ReoPro with the recommended low-dose, weight-adjusted heparin regimen was 2.8% and 1.1% in placebo-treated patients. Thrombocytopenia has been observed at higher rates following readministration (see paragraph below on Readministration).

Readministration

Human antichimeric antibody (HACA) formation appeared, generally as a low titre, in approximately 5% to 6% of patients 2 to 4 weeks after receiving a first exposure to ReoPro in the Phase III clinical studies.

Readministration of ReoPro to patients undergoing PTCA was assessed in a registry that included 1342 treatments in 1286 patients. Most patients were receiving their second ReoPro exposure; 15% were receiving the third or subsequent exposure. The overall rate of HACA positivity prior to the readministration was 6% and increased to 27% postreadministration.

In a readministration registry study of patients receiving a second or subsequent exposure to ReoPro, the incidence of any degree of thrombocytopenia was 5%, with an incidence of profound thrombocytopenia of 2% (<20,000 cell/μL). Factors associated with an increased risk of thrombocytopenia were a history of thrombocytopenia on previous ReoPro exposure, readministration within 30 days, and a positive HACA assay prior to the readministration.