Gastro-intestinal, retro-peritoneal, intracranial, haemorrhoidal and post-operative bleeding, epidural haematoma in the spinal region, haemopericardium and pulmonary (alveolar) haemorrhage have also been reported. Rates of TIMI major and intracranial bleeding in the pivotal Aggrastat studies were <2.2% and <0.1%, respectively. The most serious adverse reaction was fatal bleeding.
In the pivotal studies, administration of Aggrastat was associated with thrombocytopenia (platelet count <90,000/mm3), occurring in 1.5% of patients treated with Aggrastat and heparin. The incidence of severe thrombocytopenia (platelet count <50,000/mm3) was 0.3%. The most common non-bleeding adverse drug reactions associated with Aggrastat given concurrently with heparin were nausea (1.7%), fever (1.5%) and headache (1.1%).
b. Tabulated summary of adverse reactions
Table 2 lists the adverse reactions based on experience from six double-blind controlled clinical studies (including 1953 patients receiving Aggrastat plus heparin) as well as adverse reactions reported from post-marketing experience. Within the organ system classes, adverse reactions are listed under headings of frequency using the following categories: 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). Because post-marketing events are derived from spontaneous reports from a population of uncertain size, it is not possible to determine their exact incidence. Therefore, the frequency of these adverse reactions is categorised as not known.
Table 2: Undesirable effects in clinical studies and from post-marketing experience.
System Organ Class
Very common
Common
Uncommon
Not known
Blood and lymphatic system disorders
Acute and/or severe (<20,000/mm3) decreases in platelet counts
Immune System Disorders
Severe allergic reactions including anaphylactic reactions.
Nervous system disorders
Headache
Intracranial bleeding, spinal epidural haematoma
Cardiac disorders
Hemopericardium
Vascular disorders
Haematoma
Respiratory, thoracic and mediastinal disorders
Haemoptysis, epistaxis
Pulmonary (alveolar) haemorrhage
Gastrointestinal disorders
Nausea
Oral haemorrhage gingival haemorrhage
GI haemorrhage, haematemesis
Retroperitoneal bleeding
Skin and subcutaneous tissue disorders
Ecchymosis
Renal and urinary disorders
Haematuria
General disorders and administration site conditions
Fever
Injury, poisoning and procedural complications
Post-operative haemorrhage*
Vessel puncture site haemorrhage
Investigations
Occult blood in stool or urine
Decreases in haematocrit and haemoglobin, platelet counts <90,000/mm3
Platelet counts <50,000/mm3
*Primarily related to catheterization sites.
c. Description of selected adverse reactions
Bleeding
Both, with the Aggrastat 0.4 microgram/kg/min infusion regimen and the 25 microgram/kg dose bolus regim
