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Aggrenox (Aspirin / Extended-Release Dipyridamole) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

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 [ ]; primary endpoints included stroke (fatal or nonfatal) and death from all causes. see Clinical Studies

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 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*
  Individual Treatment Group
Body System/Preferred Term AGGRENOX ER-DP Alone ASA Alone Placebo
* Reported by ≥1% of patients during AGGRENOX treatment where the incidence was greater than in those treated with placebo.
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.
 
Total Number of Patients 1650 1654 1649 1649
Total Number (%) of Patients With at Least One On-Treatment Adverse Event

1319

(80%)

1305

(79%)

1323

(80%)

1304

(79%)

Central and Peripheral Nervous System Disorders
Headache 647 (39%) 634 (38%) 558 (34%) 543 (33%)
Convulsions 28 (2%) 15 (1%) 28 (2%) 26 (2%)
Gastrointestinal System Disorders
Dyspepsia 303 (18%) 288 (17%) 299 (18%) 275 (17%)
Abdominal Pain 289 (18%) 255 (15%) 262 (16%) 239 (14%)
Nausea 264 (16%) 254 (15%) 210 (13%) 232 (14%)
Diarrhea 210 (13%) 257 (16%) 112 (7%) 161 (10%)
Vomiting 138 (8%) 129 (8%) 101 (6%) 118 (7%)
Hemorrhage Rectum 26 (2%) 22 (1%) 16 (1%) 13 (1%)
Melena 31 (2%) 10 (1%) 20 (1%) 13 (1%)
Hemorrhoids 16 (1%) 13 (1%) 10 (1%) 10 (1%)
GI Hemorrhage 20 (1%) 5 (0%) 15 (1%) 7 (0%)
Body as a Whole - General Disorders
Pain 105 (6%) 88 (5%) 103 (6%) 99 (6%)
Fatigue 95 (6%) 93 (6%) 97 (6%) 90 (5%)
Back Pain 76 (5%) 77 (5%) 74 (4%) 65 (4%)
Accidental Injury 42 (3%) 24 (1%) 51 (3%) 37 (2%)
Malaise 27 (2%) 23 (1%) 26 (2%) 22 (1%)
Asthenia 29 (2%) 19 (1%) 17 (1%) 18 (1%)
Syncope 17 (1%) 13 (1%) 16 (1%) 8 (0%)
Psychiatric Disorders
Amnesia 39 (2%) 40 (2%) 57 (3%) 34 (2%)
Confusion 18 (1%) 9 (1%) 22 (1%) 15 (1%)
Anorexia 19 (1%) 17 (1%) 10 (1%) 15 (1%)
Somnolence 20 (1%) 13 (1%) 18 (1%) 9 (1%)
Musculoskeletal System Disorders
Arthralgia 91 (6%) 75 (5%) 91 (6%) 76 (5%)
Arthritis 34 (2%) 25 (2%) 17 (1%) 19 (1%)
Arthrosis 18 (1%) 22 (1%) 13 (1%) 14 (1%)
Myalgia 20 (1%) 16 (1%) 11 (1%) 11 (1%)
Respiratory System Disorders
Coughing 25 (2%) 18 (1%) 32 (2%) 21 (1%)
Upper Respiratory Tract Infection
16 (1%) 9 (1%) 16 (1%) 14 (1%)
Cardiovascular Disorders, General
Cardiac Failure 26 (2%) 17 (1%) 30 (2%) 25 (2%)
Platelet, Bleeding and Clotting Disorders
Hemorrhage NOS 52 (3%) 24 (1%) 46 (3%) 24 (1%)
Epistaxis 39 (2%) 16 (1%) 45 (3%) 25 (2%)
Purpura 23 (1%) 8 (0%) 9 (1%) 7 (0%)
Neoplasm
Neoplasm NOS 28 (2%) 16 (1%) 23 (1%) 20 (1%)
Red Blood Cell Disorders
Anemia 27 (2%) 16 (1%) 19 (1%) 9 (1%)

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
  Treatment Groups  
  AGGRENOX ER-DP ASA Placebo
Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dosage regimen for all treatment groups is BID  
Total Number of Patients 1650 1654 1649 1649
Patients with at least one Adverse Event that led to treatment discontinuation
417
(25%)
419
(25%)
318
(19%)
352
(21%)
Headache 165 (10%) 166 (10%) 57 (3%) 69 (4%)
Dizziness 85 (5%) 97 (6%) 69 (4%) 68 (4%)
Nausea 91 (6%) 95 (6%) 51 (3%) 53 (3%)
Abdominal Pain 74 (4%) 64 (4%) 56 (3%) 52 (3%)
Dyspepsia 59 (4%) 61 (4%) 49 (3%) 46 (3%)
Vomiting 53 (3%) 52 (3%) 28 (2%) 24 (1%)
Diarrhea 35 (2%) 41 (2%) 9 (<1%) 16 (<1%)
Stroke 39 (2%) 48 (3%) 57 (3%) 73 (4%)
Transient Ischemic Attack 35 (2%) 40 (2%) 26 (2%) 48 (3%)
Angina Pectoris 23 (1%) 20 (1%) 16 (<1%) 26 (2%)

Headache was most notable in the first month of treatment.

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. Other Adverse Events

: Allergic reaction, fever Body as a Whole

: Hypotension Cardiovascular

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

: Gastritis, ulceration and perforation Gastrointestinal

: 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 Hearing and Vestibular Disorders

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

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

: Hyperglycemia, thirst Metabolic and Nutritional Disorders

: Hematoma, gingival bleeding Platelet, Bleeding and Clotting Disorders

: Agitation Psychiatric Disorders

: Uterine hemorrhage Reproductive

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

: Taste loss Special Senses Other Disorders

: Pruritus, urticaria Skin and Appendages Disorders

: Renal insufficiency and failure, hematuria Urogenital

: Flushing Vascular (Extracardiac) Disorders

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 0.13x10 /mm. Laboratory Changes
6 3

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.

: Hypothermia, chest pain Body as a Whole

: Angina pectoris Cardiovascular

: Cerebral edema Central Nervous System

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

: Pancreatitis, Reye syndrome, hematemesis Gastrointestinal

: Hearing loss Hearing and Vestibular Disorders

: Hypersensitivity, acute anaphylaxis, laryngeal edema Immune System Disorders

: Hepatitis, hepatic failure Liver and Biliary System Disorders

: Rhabdomyolysis Musculoskeletal

: Hypoglycemia, dehydration Metabolic and Nutritional Disorders

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

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

: Tachypnea, dyspnea Respiratory

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

: Interstitial nephritis, papillary necrosis, proteinuria Urogenital

: Allergic vasculitis Vascular (Extracardiac Disorders)

: anorexia, aplastic anemia, migraine, pancytopenia, thrombocytosis. Other Adverse Events



REPORTS OF SUSPECTED AGGRENOX SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Aggrenox. The information is not vetted and should not be considered as verified clinical evidence.

Possible Aggrenox side effects / adverse reactions in 72 year old female

Reported by a consumer/non-health professional from United States on 2011-10-04

Patient: 72 year old female weighing 63.5 kg (139.7 pounds)

Reactions: Vomiting, Nausea, Headache

Suspect drug(s):
Aggrenox



Possible Aggrenox side effects / adverse reactions in 67 year old female

Reported by a pharmacist from United States on 2011-10-06

Patient: 67 year old female weighing 66.0 kg (145.2 pounds)

Reactions: Subdural Haematoma, Brain Midline Shift

Adverse event resulted in: hospitalization

Suspect drug(s):
Aggrenox

Other drugs received by patient: Potassium Chloride; Lipitor; Lisinopril; Coreg



Possible Aggrenox side effects / adverse reactions in 86 year old male

Reported by a pharmacist from United States on 2011-10-06

Patient: 86 year old male weighing 68.1 kg (149.8 pounds)

Reactions: Haemoglobin Decreased, Incontinence, Haemorrhage, Urinary Tract Infection, Oesophagitis Ulcerative, Dizziness, Haematemesis

Adverse event resulted in: hospitalization

Suspect drug(s):
Lovenox
    Dosage: 40mg qd x week 4 daily sq/po recent
    Administration route: Oral
    Indication: Thrombosis Prophylaxis

Aspirin
    Dosage: 81mg daily po chronic
    Administration route: Oral

Aggrenox
    Dosage: 1 capsule bid po chronic
    Administration route: Oral

Other drugs received by patient: Tylenol-500; Requip; Lovastatin; VIT B12; Miralax; Flomax; Norvasc; Claritin; Finasteride; Senokat; Timolol; Senokot; Protonix



See index of all Aggrenox side effect reports >>

Drug label data at the top of this Page last updated: 2013-12-05

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