AGGRENOX SIDE EFFECTS
- Generic Name: aspirin, extended-release dipyridamole capsules
- Brand Name: Aggrenox
- Drug Class: Antiplatelet Agents, Hematologic, Antiplatelet Agents, Hematologic
SIDE EFFECTS
The following adverse reactions are discussed elsewhere in the labeling:
- Hypersensitivity.
- Allergy.
- Risk of Bleeding.
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; 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, extended-release 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 annualized event rate for adverse events that occurred in 1%/year or more of patients treated with AGGRENOX where the incidence was also at least 1%/year 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 ESPS2a
| Body System/Preferred Term | Individual Treatment Group | |||
| AGGRENOX n (%/year)b | ER-DP Alone n (%/year)b | ASA Alone n (%/year)b | Placebo n (%/year)b | |
| Total Number of Patients | 1650 | 1654 | 1649 | 1649 |
| Central and Peripheral Nervous System Disorders | ||||
| Headache | 647 (28.25) | 634 (27.91) | 558 (22.10) | 543 (22.29) |
| Gastrointestinal System Disorders | ||||
| Dyspepsia | 303(13.23) | 288(12.68) | 299(11.84) | 275(11.29) |
| Abdominal Pain | 289(12.62) | 255(11.22) | 262(10.38) | 239(9.81) |
| Nausea | 264(11.53) | 254(11.18) | 210(8.32) | 232(9.53) |
| Diarrhea | 210(9.17) | 257(1131) | 112(4.44) | 161(6.61) |
| Vomiting | 138(6.03) | 129(5.68) | 101(4.00) | 118(4.84) |
| Platelet, Bleeding and Clotting Disorders | ||||
| Hemorrhage NOS | 52(2.27) | 24(1.06) | 46(182) | 24(0.99) |
| aReported by ≥1%/year of patients during AGGRENOX treatment where the incidence was at least 1%/year greater than in those treated with placebo. bAnnual event rate per 100 pt-years = 100* number of subjects with event/subject-years. Subject-years is defined as cumulative number of days on treatment divided by 365.25. Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dosage regimen for all treatment groups is BID. NOS = not otherwise specified. |
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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
| Treatment Groups | ||||
| AGGRENOX n (%/year)b | ER-DP n (%/year)b | ASA n (%/year)b | Placebo n (%/year)b | |
| Total Number of Patients | 1650 | 1654 | 1649 | 1649 |
| Patients with at least one Adverse Event that led to treatment discontinuation | 417(18.21) | 419(18.44) | 318(12.59) | 352(14.45) |
| Headache | 165(7.20) | 166(7.31) | 57(2.26) | 69(2.83) |
| Nausea | 91(3.97) | 95(4.18) | 51(2.02) | 53(2.18) |
| Abdominal Pain | 74(3.23) | 64(2.82) | 56(2.22) | 52(2.13) |
| Vomiting | 53(2.31) | 52(2.29) | 28(111) | 24(0.99) |
| aReported by ≥1%/year of patients during AGGRENOX treatment where the incidence was at least 1%/year greater than in those treated with placebo. bAnnual event rate per 100 pt-years = 100* number of subjects with event/subject-years. Subject-years is defined as cumulative number of days on treatment divided by 365.25. Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dosage regimen for all treatment groups is BID. |
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Headache was most notable in the first month of treatment.
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, allergic reaction, syncope
Cardiovascular: Angina pectoris, hypotension
Central Nervous System: Cerebral edema, dizziness, cerebral hemorrhage, intracranial hemorrhage, subarachnoid hemorrhage
Fluid and Electrolyte: Hyperkalemia, metabolic acidosis, respiratory alkalosis, hypokalemia
Gastrointestinal: Pancreatitis, Reye syndrome, hematemesis, gastritis, ulceration and perforation, hemorrhage rectum, melena, GI hemorrhage
Hearing and Vestibular Disorders: Hearing loss
Heart Rate and Rhythm Disorders: Tachycardia, palpitation
Immune System Disorders: Hypersensitivity, acute anaphylaxis, laryngeal edema
Liver and Biliary System Disorders: Hepatitis, hepatic failure, cholelithiasis, jaundice, hepatic function abnormal
Musculoskeletal: Rhabdomyolysis, myalgia
Metabolic and Nutritional Disorders: Hypoglycemia, dehydration
Platelet, Bleeding and Clotting Disorders: Prolongation of the prothrombin time, disseminated intravascular coagulation, coagulopathy, thrombocytopenia, hematoma, gingival bleeding, epistaxis, purpura
Psychiatric Disorders: Confusion, agitation
Respiratory: Tachypnea, dyspnea, hemoptysis
Skin and Appendages Disorders: Rash, alopecia, angioedema, Stevens-Johnson syndrome, skin hemorrhages such as bruising, ecchymosis, and hematoma, pruritus, urticaria, and drug reaction with eosinophilia and systemic symptoms (DRESS)
Urogenital: Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, hematuria
Vascular (Extracardiac) Disorders: Allergic vasculitis, flushing
Other Adverse Events: Anorexia, aplastic anemia, migraine, pancytopenia, thrombocytosis.
SRC: NLM .