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

 
 



ADVERSE REACTIONS

A 24-month, multicenter, double-blind, randomized study (ESPS2) was conducted to compare the efficacy and safety of AGGRENOX capsules 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 2 presents the incidence of adverse events that occurred in 1% or more of patients treated with AGGRENOX capsules 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 2   Incidence of Adverse Events in ESPS2*
Individual Treatment Group
Body System/Preferred TermAGGRENOXER-DP AloneASA AlonePlacebo
* 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 Patients1650165416491649
Total Number (%) of Patients With at
   Least One On-Treatment Adverse
   Event


1319


(79.9%)


1305


(78.9%)


1323


(80.2%)


1304


(79.1%)
Central & Peripheral Nervous System Disorders
   Headache647(39.2%)634(38.3%)558(33.8%)543(32.9%)
   Convulsions28(1.7%)15(0.9%)28(1.7%)26(1.6%)
Gastro-Intestinal System Disorders
   Dyspepsia303(18.4%)288(17.4%)299(18.1%)275(16.7%)
   Abdominal Pain289(17.5%)255(15.4%)262(15.9%)239(14.5%)
   Nausea264(16.0%)254(15.4%)210(12.7%)232(14.1%)
   Diarrhea210(12.7%)257(15.5%)112(6.8%)161(9.8%)
   Vomiting138(8.4%)129(7.8%)101(6.1%)118(7.2%)
   Hemorrhage Rectum26(1.6%)22(1.3%)16(1.0%)13(0.8%)
   Melena31(1.9%)10(0.6%)20(1.2%)13(0.8%)
   Hemorrhoids16(1.0%)13(0.8%)10(0.6%)10(0.6%)
   GI Hemorrhage20(1.2%)5(0.3%)15(0.9%)7(0.4%)
Body as a Whole - General Disorders
   Pain105(6.4%)88(5.3%)103(6.2%)99(6.0%)
   Fatigue95(5.8%)93(5.6%)97(5.9%)90(5.5%)
   Back Pain76(4.6%)77(4.7%)74(4.5%)65(3.9%)
   Accidental Injury42(2.5%)24(1.5%)51(3.1%)37(2.2%)
   Malaise27(1.6%)23(1.4%)26(1.6%)22(1.3%)
   Asthenia29(1.8%)19(1.1%)17(1.0%)18(1.1%)
   Syncope17(1.0%)13(0.8%)16(1.0%)8(0.5%)
Psychiatric Disorders
   Amnesia39(2.4%)40(2.4%)57(3.5%)34(2.1%)
   Confusion18(1.1%)9(0.5%)22(1.3%)15(0.9%)
   Anorexia19(1.2%)17(1.0%)10(0.6%)15(0.9%)
   Somnolence20(1.2%)13(0.8%)18(1.1%)9(0.5%)
Musculoskeletal System Disorders
   Arthralgia91(5.5%)75(4.5%)91(5.5%)76(4.6%)
   Arthritis34(2.1%)25(1.5%)17(1.0%)19(1.2%)
   Arthrosis18(1.1%)22(1.3%)13(0.8%)14(0.8%)
   Myalgia20(1.2%)16(1.0%)11(0.7%)11(0.7%)
Respiratory System Disorders
   Coughing25(1.5%)18(1.1%)32(1.9%)21(1.3%)
   Upper Respiratory Tract
   Infection
16(1.0%)9(0.5%)16(1.0%)14(0.8%)
Cardiovascular Disorders, General
   Cardiac Failure26(1.6%)17(1.0%)30(1.8%)25(1.5%)
Platelet, Bleeding & Clotting Disorders
   Hemorrhage NOS52(3.2%)24(1.5%)46(2.8%)24(1.5%)
   Epistaxis39(2.4%)16(1.0%)45(2.7%)25(1.5%)
   Purpura23(1.4%)8(0.5%)9(0.5%)7(0.4%)
Neoplasm
   Neoplasm NOS28(1.7%)16(1.0%)23(1.4%)20(1.2%)
Red Blood Cell Disorders
   Anemia27(1.6%)16(1.0%)19(1.2%)9(0.5%)

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 3).

Table 3   Incidence of Adverse Events that Led to the Discontinuation of Treatment: Adverse Events with an Incidence of ≥1% in the AGGRENOX group
Treatment Groups
AGGRENOXER-DPASAPlacebo
Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dosage regimen for all treatment groups is BID
Total Number of Patients1650165416491649
Patients with at least one Adverse Event
that led to treatment discontinuation

417

(25%)

419

(25%)

318

(19%)

352

(21%)
   Headache165(10%)166(10%)57(3%)69(4%)
   Dizziness85(5%)97(6%)69(4%)68(4%)
   Nausea91(6%)95(6%)51(3%)53(3%)
   Abdominal Pain74(4%)64(4%)56(3%)52(3%)
   Dyspepsia59(4%)61(4%)49(3%)46(3%)
   Vomiting53(3%)52(3%)28(2%)24(1%)
   Diarrhea35(2%)41(2%)9(<1%)16(<1%)
   Stroke39(2%)48(3%)57(3%)73(4%)
   Transient Ischemic Attack35(2%)40(2%)26(2%)48(3%)
   Angina Pectoris23(1%)20(1%)16(<1%)26(2%)

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® (aspirin/extended-release dipyridamole) capsules in the ESPS2 study and that were medically judged to be possibly related to either dipyridamole or aspirin are listed below (see WARNINGS).

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

The following is a list of additional adverse reactions that have been reported either in the literature or are from postmarketing 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.

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's syndrome, hematemesis

Hearing and Vestibular Disorders: Hearing loss

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.

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.



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: 2007-06-19

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