However, animal studies are insufficient to draw conclusions with respect to reproductive toxicity in humans.
a. Summary of safety profile
The most common adverse reaction reported during therapy with Aggrastat, when used concomitantly with heparin, aspirin and other oral anti-platelet agents, was bleeding, which usually involved mild mucocutaneous bleeding or mild catheterization-site bleeding.
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.
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System Organ Class
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Very common
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Common
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Uncommon
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Not known
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Blood and lymphatic system disorders
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|
|
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Acute and/or severe (<20,000/mm3) decreases in platelet counts
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|
Immune System Disorders
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|
|
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Severe allergic reactions including anaphylactic reactions.
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Nervous system disorders
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Headache
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|
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Intracranial bleeding, spinal epidural haematoma
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|
Cardiac disorders
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