SIDE EFFECTS

The following adverse reactions are discussed elsewhere in the labeling:

• Hypersensitivity [see CONTRAINDICATIONS].
• Allergy [see CONTRAINDICATIONS].
• Risk of Bleeding [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The efficacy and safety of AGGRENOX was established in the European Stroke Prevention Study-2 (ESPS2). ESPS2 was a double-blind, placebo controlled study that evaluated 6602 patients over the age of 18 years who had a previous ischemic stroke or transient ischemic attack within ninety days prior to entry. Patients were randomized to either AGGRENOX, aspirin, ER-DP, or placebo [see Clinical Studies]; primary endpoints included stroke (fatal or nonfatal) and death from all causes.

This 24-month, multicenter, double-blind, randomized study (ESPS2) was conducted to compare the efficacy and safety of AGGRENOX with placebo, extendedrelease dipyridamole alone and aspirin alone. The study was conducted in a total of 6602 male and female patients who had experienced a previous ischemic stroke or transient ischemia of the brain within three months prior to randomization.

Table 1 presents the incidence of adverse events that occurred in 1% or more of patients treated with AGGRENOX where the incidence was also greater than in those patients treated with placebo. There is no clear benefit of the dipyridamole/aspirin combination over aspirin with respect to safety.

Table 1 : Incidence of Adverse Events in ESPS2*

Discontinuation due to adverse events in ESPS2 was 25% for AGGRENOX, 25% for extended-release dipyridamole, 19% for aspirin, and 21% for placebo (refer to Table 2)

Table 2 : Incidence of Adverse Events that Led to the Discontinuation of Treatment: Adverse Events with an Incidence of ≥ 1% in the AGGRENOX Group

Headache was most notable in the first month of treatment.

Other Adverse Events

Adverse reactions that occurred in less than 1% of patients treated with AGGRENOX in the ESPS2 study and that were medically judged to be possibly related to either dipyridamole or aspirin are listed below.

Body as a Whole: Allergic reaction, fever

Cardiovascular: Hypotension

Central Nervous System: Coma, dizziness, paresthesia, cerebral hemorrhage, intracranial hemorrhage, subarachnoid hemorrhage

Gastrointestinal: Gastritis, ulceration and perforation

Hearing and Vestibular Disorders: Tinnitus, and deafness. Patients with high frequency hearing loss may have difficulty perceiving tinnitus. In these patients, tinnitus cannot be used as a clinical indicator of salicylism

Heart Rate and Rhythm Disorders: Tachycardia, palpitation, arrhythmia, supraventricular tachycardia

Liver and Biliary System Disorders: Cholelithiasis, jaundice, hepatic function abnormal

Metabolic and Nutritional Disorders: Hyperglycemia, thirst

Platelet, Bleeding and Clotting Disorders: Hematoma, gingival bleeding

Psychiatric Disorders: Agitation

Reproductive: Uterine hemorrhage

Respiratory: Hyperpnea, asthma, bronchospasm, hemoptysis, pulmonary edema

Special Senses Other Disorders: Taste loss

Skin and Appendages Disorders: Pruritus, urticaria

Urogenital: Renal insufficiency and failure, hematuria

Vascular (Extracardiac) Disorders: Flushing

Laboratory Changes

Over the course of the 24-month study (ESPS2), patients treated with AGGRENOX showed a decline (mean change from baseline) in hemoglobin of 0.25 g/dL, hematocrit of 0.75%, and erythrocyte count of 0.13x106/mm³.

Post-Marketing Experience

The following is a list of additional adverse reactions that have been reported either in the literature or are from post-marketing spontaneous reports for either dipyridamole or aspirin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to AGGRENOX.

Body as a Whole: Hypothermia, chest pain

Cardiovascular: Angina pectoris

Central Nervous System: Cerebral edema

Fluid and Electrolyte: Hyperkalemia, metabolic acidosis, respiratory alkalosis, hypokalemia

Gastrointestinal: Pancreatitis, Reye syndrome, hematemesis

Hearing and Vestibular Disorders: Hearing loss

Immune System Disorders: Hypersensitivity, acute anaphylaxis, laryngeal edema

Liver and Biliary System Disorders: Hepatitis, hepatic failure

Musculoskeletal: Rhabdomyolysis

Metabolic and Nutritional Disorders: Hypoglycemia, dehydration

Platelet, Bleeding and Clotting Disorders: Prolongation of the prothrombin time, disseminated intravascular coagulation, coagulopathy, thrombocytopenia

Reproductive: Prolonged pregnancy and labor, stillbirths, lower birth weight infants, antepartum and postpartum bleeding

Respiratory: Tachypnea, dyspnea

Skin and Appendages Disorders: Rash, alopecia, angioedema, Stevens-Johnson syndrome, skin hemorrhages such as bruising, ecchymosis, and hematoma

Urogenital: Interstitial nephritis, papillary necrosis, proteinuria

Vascular (Extracardiac Disorders): Allergic vasculitis

Other adverse events: anorexia, aplastic anemia, migraine, pancytopenia, thrombocytosis.

Read the entire FDA prescribing information for Aggrenox (Aspirin, Extended-Release Dipyridamole Capsules) »