Aggrastat Side Effects

Please note - some side effects for Aggrastat may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Aggrastat - for the Consumer

Aggrastat

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Aggrastat:

Dizziness; headache; leg pain; nausea; pelvic pain; sweating.

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bruising, pain, redness, or swelling at the injection site; changes in heart rhythm; chills; difficulty urinating; fainting; fever; numbness; tingling or weakness in the arms or legs; unusual bruising or bleeding (eg, bleeding gums, nosebleeds, bleeding in the eye, blood in the urine, black or tarry stools, coughing up blood, vomiting blood or material that looks like coffee ground).

Aggrastat Side Effects - for the Professional

Aggrastat

In clinical trials, 1946 patients received Aggrastat in combination with heparin and 2002 patients received Aggrastat alone. Duration of exposure was up to 116 hours. 43% of the population was >65 years of age and approximately 30% of patients were female.

BLEEDING

The most common drug-related adverse event reported during therapy with Aggrastat when used concomitantly with heparin and aspirin, was bleeding (usually reported by the investigators as oozing or mild). The incidences of major and minor bleeding using the TIMI criteria in the PRISM-PLUS and RESTORE studies are shown below.

There were no reports of intracranial bleeding in the PRISM-PLUS study for Aggrastat in combination with heparin or in the heparin control group. The incidence of intracranial bleeding in the RESTORE study was 0.1% for Aggrastat in combination with heparin and 0.3% for the control group (which received heparin). In the PRISM-PLUS study, the incidences of retroperitoneal bleeding reported for Aggrastat in combination with heparin, and for the heparin control group were 0.0% and 0.1%, respectively. In the RESTORE study, the incidences of retroperitoneal bleeding reported for Aggrastat in combination with heparin, and the control group were 0.6% and 0.3%, respectively. The incidences of TIMI major gastrointestinal and genitourinary bleeding for Aggrastat in combination with heparin in the PRISM-PLUS study were 0.1% and 0.1%, respectively; the incidences in the RESTORE study for Aggrastat in combination with heparin were 0.2% and 0.0%, respectively.

The incidence rates of TIMI major bleeding in patients undergoing percutaneous procedures in PRISM-PLUS are shown below.

The incidence rates of TIMI major bleeding (in some cases possibly reflecting hemodilution rather than actual bleeding) in patients undergoing CABG in the PRISM-PLUS and RESTORE studies within one day of discontinuation of Aggrastat are shown below.

Female patients and elderly patients receiving Aggrastat with heparin or heparin alone had a higher incidence of bleeding complications than male patients or younger patients. The incremental risk of bleeding in patients treated with Aggrastat in combination with heparin over the risk in patients treated with heparin alone was comparable regardless of age or gender. No dose adjustment is recommended for these populations.

NON-BLEEDING

The incidences of non-bleeding adverse events that occurred at an incidence of >1% and numerically higher than control, regardless of drug relationship, are shown below:

Other non-bleeding side effects (considered at least possibly related to treatment) reported at a >1% rate with Aggrastat administered concomitantly with heparin were nausea, fever, and headache; these side effects were reported at a similar rate in the heparin group.

In clinical studies, the incidences of adverse events were generally similar among different races, patients with or without hypertension, patients with or without diabetes mellitus, and patients with or without hypercholesteremia.

The overall incidence of non-bleeding adverse events was higher in female patients (compared to male patients) and older patients (compared to younger patients). However, the incidences of non-bleeding adverse events in these patients were comparable between the Aggrastat with heparin and the heparin alone groups.

Allergic Reactions/Readministration

Although no patients in the clinical trial database developed anaphylaxis and/or hives requiring discontinuation of the infusion of tirofiban, anaphylaxis has been reported in post-marketing experience. No information is available regarding the development of antibodies to tirofiban.

Laboratory Findings

The most frequently observed laboratory adverse events in patients receiving Aggrastat concomitantly with heparin were related to bleeding. Decreases in hemoglobin (2.1%) and hematocrit (2.2%) were observed in the group receiving Aggrastat compared to 3.1% and 2.6%, respectively, in the heparin group. Increases in the presence of urine and fecal occult blood were also observed (10.7% and 18.3%, respectively) in the group receiving Aggrastat compared to 7.8% and 12.2%, respectively, in the heparin group.

Patients treated with Aggrastat, with heparin, were more likely to experience decreases in platelet counts than the control group. These decreases were reversible upon discontinuation of Aggrastat. The percentage of patients with a decrease of platelets to <90,000/mm3 was 1.5%, compared with 0.6% in the patients who received heparin alone. The percentage of patients with a decrease of platelets to <50,000/mm3 was 0.3%, compared with 0.1% of the patients who received heparin alone. Platelet decreases have been observed in patients with no prior history of thrombocytopenia upon readministration of GP IIb/IIIa receptor antagonists.

Post-Marketing Experience

The following additional adverse reactions have been reported in post-marketing experience: Bleeding: Intracranial bleeding, retroperitoneal bleeding, hemopericardium, pulmonary (alveolar) hemorrhage, and spinal-epidural hematoma. Fatal bleeding events have been reported;Body as a Whole: Acute and/or severe decreases in platelet counts which may be associated with chills, low-grade fever, or bleeding complications;Hypersensitivity: Severe allergic reactions including anaphylactic reactions. The reported cases have occurred during the first day of tirofiban infusion, during initial treatment, and during readministration of tirofiban. Some cases have been associated with severe thrombocytopenia (platelet counts <10,000/mm3).

Side Effects by Body System

General

Prior to approval by the FDA the efficacy and safety of tirofiban was evaluated in 1,946 patients who received both tirofiban and heparin and 2,002 patients who received tirofiban alone. The average duration of exposure was 116 hours. Forty-three percent of the patients were greater than 65 years old and approximately 30% of the patients were female. In clinical studies, the incidences of side effects were generally similar among different races, and were not more prevalent among patients with hypertension or diabetes or hypercholesterolemia. The most common and potentially significant side effect was bleeding; non-bleeding side effects occurred in up to approximately 6% of patients. The overall incidence of non-bleeding side effects was higher in female and older patients compared with male or younger patients. However, the incidence of non-bleeding side effects was similar among all patients who received tirofiban + heparin versus heparin alone.

Hematologic

Hematologic lab changes in patients who received tirofiban + heparin versus heparin alone have included decreases in hemoglobin in 2.1% and 3.1% and hematocrit in 2.2% and 2.6%, increases in microhematuria in 10.7% and 7.8%, and increases in fecal occult blood in 18.3% and 12.2% of patients, respectively.

The incidence of thrombocytopenia (less than 100,000 cells/mcL) associated with tirofiban is 1.1% to 1.9%, while severe thrombocytopenia (less than 50,000 cells/mcL) has been reported in 0.2% to 0.5% of patients in clinical trials.

Decreases in platelet concentrations have been associated with the use of heparin alone. The incidences of reversible decreases in platelet concentrations among patients treated the tirofiban + heparin versus heparin alone in controlled trials were 1.5% and 0.6% (platelet counts less than 90,000/mm3) and 0.3% and 0.1% (platelet counts less than 50,000/mm3) of patients, respectively.

Risk factors for bleeding events in patients treated with glycoprotein (GP) IIb/IIIa inhibitors undergoing percutaneous coronary intervention have been identified and include advanced age, renal dysfunction, female gender, peripheral vascular disease, lower body weight, duration of GP IIb/IIIa inhibitor infusion, baseline platelet count, lower baseline hemoglobin, diabetes, and elevated peak activated clotting time. According to one study (CRUSADE trial) involving patients with non-ST-segment elevation acute coronary syndrome treated with a GP IIb/IIIa inhibitor, women are at a greater risk of bleeding than men, primarily because of excessive dosing.

The most common and potentially serious side effect associated with the use of tirofiban (and heparin and aspirin) has been bleeding. The incidences of major and minor bleeding in the PRISM-PLUS trial were 1.4% and 10.5%, respectively, and the incidence of transfusions was 4.0%. The incidences of these events in the RESTORE trial were 2.2%, 12.0%, and 4.3%. All incidences were greater than those observed among patients who were given heparin alone. There were no reports of intracranial hemorrhage (ICH) in the PRISM-PLUS trial, but the incidences of ICH associated with the use of tirofiban + heparin and heparin alone in the RESTORE trial were 0.1% and 0.3%. For patients who received tirofiban + heparin versus heparin alone, the following incidences were observed: retroperitoneal bleeding, 0% and 0.1% (PRISM-PLUS) and 0.6% and 0.3% (RESTORE), respectively; and gastrointestinal or genitourinary bleeding, 0.1% and 0.1% (PRISM-PLUS) and 0.2% and 0.0%, respectively. The incidences of major bleeding in patients undergoing PTCA in PRISM-PLUS among patients who were given tirofiban + heparin versus heparin alone were 0.3% and 0.1% (pre-PTCA), 1.3% and 0.7% (following angiography), and 2.5% and 2.2% (following PTCA), respectively. Female and elderly patients in either group had a higher incidence of bleeding compared with male or younger patients. Concomitant use of heparin did not confer significant additional risk of bleeding in any group.

Cardiovascular

Cardiovascular side effects in patients who received tirofiban + heparin versus heparin alone have included edema or swelling in 2% and 1%, bradycardia in 4% and 3%, and coronary artery dissection in 5% and 4% of patients, respectively. Many side effects may in fact be attributed to underlying disease or the risks of procedures patients were undergoing.

Analysis of one study (TARGET trial) indicates that patients with renal dysfunction undergoing PCI and receiving a GP IIb/IIIa inhibitor (i.e., tirofiban, abciximab) are at a higher risk of developing ischemic complications (30-day death, myocardial infarction,urgent revascularization) than patients with normal creatinine clearance.

Musculoskeletal

Musculoskeletal side effects in patients who received tirofiban + heparin versus heparin alone have included pelvic pain in 6% and 5% and general leg pain in 3% and 2% of patients, respectively. These side effects may in fact be attributed to complications associated with femoral artery access associated with angiography.

Nervous system

Nervous system side effects in patients who received tirofiban + heparin versus heparin alone have included vasovagal reactions in 2% and 1%, dizziness in 3% and 2%, and sweating in 2% and 1% of patients, respectively. Headache has been associated with the use of tirofiban + heparin in approximately 1% of patients (and in a similar fraction of patients treated with heparin alone).

Gastrointestinal

The only gastrointestinal side effect noted among patients in controlled trials was nausea, observed in approximately 1% of patients.

Hypersensitivity

Hypersensitivity reactions were remarkably absent in clinical studies prior to FDA approval. There were no recorded instances of anaphylaxis or hives. There are no data regarding the development of anti-tirofiban antibodies; very few patients have received this drug twice.

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