Aggrenox
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Aggrenox Precautions
Serious side effects have been reported with Aggrenox, including the following:
- Bleeding. Tell your health care provider right away if you have some or all of the following symptoms of bleeding:
- Black or bloody stools
- Vomiting blood or experiencing coffee ground-looking vomit
- Bruising that does not go away
- Worsening of liver disease in those with severe liver disease
- Worsening of kidney disease in those with severe kidney disease
- Harm to unborn children when used in pregnant women, especially in the third trimester
- Heart disease, as this medication can cause/worsen chest pain
- Low blood pressure, as this medication can lower blood pressure
Do not take Aggrenox if you:
- are allergic to aspirin, dipyridamole, or to any of its ingredients
- are allergic to non-steroidal anti-inflammatory drugs (NSAIDs)
- have asthma or nasal polyps
- are younger than 18 years of age and have a viral infection
Aggrenox and Lactation
Tell your doctor if you are breastfeeding or plan to breastfeed.
Aggrenox has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from this medication, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.
What is aspirin and dipyridamole?
Aspirin is in a group of drugs called salicylates (sa-LIS-il-ates). It works by reducing substances in the body that cause pain, fever, and inflammation.
Dipyridamole keeps platelets in your blood from sticking together to form clots.
Aspirin and dipyridamole is a combination medicine used to reduce the risk of stroke in people who have had blood clots or a "mini-stroke" (also called a transient ischemic attack or TIA).
Aspirin and dipyridamole may also be used for purposes not listed in this medication guide.
Before Using Aggrenox
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:
Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Pediatric
Appropriate studies have not been performed on the relationship of age to the effects of aspirin and dipyridamole combination in the pediatric population. Because of aspirin's toxicity, use in children and teenagers is not recommended.
Geriatric
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of aspirin and dipyridamole combination in the elderly.
Pregnancy
Pregnancy Category | Explanation | |
---|---|---|
All Trimesters | D | Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk. |
Breast Feeding
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with Medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- Defibrotide
- Dichlorphenamide
- Influenza Virus Vaccine, Live
- Ketorolac
- Riociguat
Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Abciximab
- Acarbose
- Aceclofenac
- Acemetacin
- Alipogene Tiparvovec
- Alteplase, Recombinant
- Amiloride
- Amineptine
- Amitriptyline
- Amitriptylinoxide
- Amoxapine
- Amtolmetin Guacil
- Anagrelide
- Anisindione
- Apixaban
- Ardeparin
- Argatroban
- Bemiparin
- Bendroflumethiazide
- Benzthiazide
- Betrixaban
- Bivalirudin
- Bromfenac
- Bufexamac
- Bumetanide
- Celecoxib
- Certoparin
- Chlorothiazide
- Chlorpropamide
- Chlorthalidone
- Choline Salicylate
- Cilostazol
- Citalopram
- Clomipramine
- Clonixin
- Clopamide
- Clopidogrel
- Cyclopenthiazide
- Cyclosporine
- Dabigatran Etexilate
- Dalteparin
- Danaparoid
- Desipramine
- Desirudin
- Desmopressin
- Desvenlafaxine
- Dexibuprofen
- Dexketoprofen
- Diazoxide
- Dibenzepin
- Diclofenac
- Dicumarol
- Diflunisal
- Digoxin
- Dipyrone
- Dothiepin
- Doxepin
- Droxicam
- Duloxetine
- Edoxaban
- Enoxaparin
- Eplerenone
- Eptifibatide
- Escitalopram
- Ethacrynic Acid
- Etodolac
- Etofenamate
- Etoricoxib
- Felbinac
- Fenoprofen
- Fepradinol
- Feprazone
- Feverfew
- Floctafenine
- Flufenamic Acid
- Fluoxetine
- Flurbiprofen
- Fluvoxamine
- Fondaparinux
- Furosemide
- Ginkgo
- Glimepiride
- Glipizide
- Glyburide
- Gossypol
- Heparin
- Hydrochlorothiazide
- Hydroflumethiazide
- Ibuprofen
- Imipramine
- Indapamide
- Indomethacin
- Ketoprofen
- Ketorolac
- Lepirudin
- Levomilnacipran
- Lithium
- Lofepramine
- Lornoxicam
- Loxoprofen
- Lumiracoxib
- Meclofenamate
- Mefenamic Acid
- Melitracen
- Meloxicam
- Metformin
- Methotrexate
- Methyclothiazide
- Metolazone
- Milnacipran
- Morniflumate
- Nabumetone
- Nadroparin
- Naproxen
- Nateglinide
- Nefazodone
- Nepafenac
- Nicorandil
- Niflumic Acid
- Nimesulide
- Nimesulide Beta Cyclodextrin
- Nortriptyline
- Opipramol
- Oxaprozin
- Oxyphenbutazone
- Parecoxib
- Parnaparin
- Paroxetine
- Pemetrexed
- Pentosan Polysulfate Sodium
- Pentoxifylline
- Phenindione
- Phenprocoumon
- Phenylbutazone
- Piketoprofen
- Piracetam
- Piroxicam
- Polythiazide
- Pralatrexate
- Pranoprofen
- Prasugrel
- Proglumetacin
- Propyphenazone
- Proquazone
- Protein C
- Protriptyline
- Repaglinide
- Reteplase, Recombinant
- Reviparin
- Rivaroxaban
- Rofecoxib
- Salicylic Acid
- Salsalate
- Sertraline
- Sodium Salicylate
- Spironolactone
- Streptokinase
- Sulfinpyrazone
- Sulindac
- Tacrolimus
- Tenoxicam
- Tianeptine
- Tiaprofenic Acid
- Ticagrelor
- Ticlopidine
- Tinzaparin
- Tirofiban
- Tolazamide
- Tolbutamide
- Tolfenamic Acid
- Tolmetin
- Torsemide
- Treprostinil
- Triamterene
- Trichlormethiazide
- Trimipramine
- Valdecoxib
- Varicella Virus Vaccine
- Venlafaxine
- Vilazodone
- Vortioxetine
- Warfarin
- Xipamide
Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Acebutolol
- Adenosine
- Atenolol
- Betamethasone
- Betaxolol
- Bisoprolol
- Captopril
- Carteolol
- Carvedilol
- Celiprolol
- Cortisone
- Delapril
- Dexamethasone
- Enalaprilat
- Enalapril Maleate
- Esmolol
- Imidapril
- Labetalol
- Levobunolol
- Lisinopril
- Methylprednisolone
- Metipranolol
- Metoprolol
- Nadolol
- Nebivolol
- Nitroglycerin
- Oxprenolol
- Paramethasone
- Penbutolol
- Pindolol
- Practolol
- Prednisolone
- Prednisone
- Probenecid
- Propranolol
- Sotalol
- Streptokinase
- Tamarind
- Temocapril
- Tenecteplase
- Timolol
- Triamcinolone
- Valproic Acid
Interactions with Food/Tobacco/Alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
- Ethanol
Other Medical Problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:
- Alcohol use (3 or more drinks per day) or
- Bleeding problems or
- Liver disease, severe or
- Stomach ulcer, history of—May cause side effects to become worse.
- Angina (severe chest pain), unstable or
- Heart attack, recent or
- Heart disease (e.g., coronary artery disease) or
- Hypotension (low blood pressure) or
- Kidney disease, severe or
- Myasthenia gravis (severe muscle weakness)—Use with caution. May make these conditions worse.
- Asthma with nasal polyps and rhinitis, history of or
- Nonsteroidal antiinflammatory drug (NSAID) allergy (e.g., diclofenac, ibuprofen, naproxen, Advil®, Aleve®, Celebrex®, Voltaren®) or
- Reye's syndrome (metabolic disorder)—Should not be used in patients with these conditions.
Contraindications
Hypersensitivity
Aggrenox is contraindicated in patients with known hypersensitivity to any of the product components.
Allergy
Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug (NSAID) products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema or bronchospasm.
Reye Syndrome
Do not use aspirin in children or teenagers with viral infections because of the risk of Reye syndrome.
Adverse reactions
The following adverse reactions are discussed elsewhere in the labeling:
- Hypersensitivity [see Contraindications (4.1)]
- Allergy [see Contraindications (4.2)]
- Risk of Bleeding [see Warnings and Precautions (5.1)]
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 (14)]; 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 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.
Individual Treatment Group | ||||||||
---|---|---|---|---|---|---|---|---|
Aggrenox | ER-DP Alone | ASA Alone | Placebo | |||||
Body System/Preferred Term | ||||||||
aReported 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. | ||||||||
1650 | 1654 | 1649 | 1649 | |||||
Total Number of Patients | ||||||||
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)
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.
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.
Description
Aggrenox is a combination antiplatelet agent intended for oral administration. Each hard gelatin capsule contains 200 mg dipyridamole in an extended-release form and 25 mg aspirin, as an immediate-release sugar-coated tablet. In addition, each capsule contains the following inactive ingredients: acacia, aluminum stearate, colloidal silicon dioxide, corn starch, dimethicone, hypromellose, hypromellose phthalate, lactose monohydrate, methacrylic acid copolymer, microcrystalline cellulose, povidone, stearic acid, sucrose, talc, tartaric acid, titanium dioxide and triacetin.
Each capsule shell contains gelatin, red iron oxide and yellow iron oxide, titanium dioxide and water.
Dipyridamole
Dipyridamole is an antiplatelet agent chemically described as 2,2',2'',2'''-[(4,8-Dipiperidinopyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]-tetraethanol. It has the following structural formula:
Dipyridamole is an odorless yellow crystalline substance, having a bitter taste. It is soluble in dilute acids, methanol and chloroform, and is practically insoluble in water.
Aspirin
The antiplatelet agent aspirin (acetylsalicylic acid) is chemically known as benzoic acid, 2- (acetyloxy)-, and has the following structural formula:
Aspirin is an odorless white needle-like crystalline or powdery substance. When exposed to moisture, aspirin hydrolyzes into salicylic and acetic acids, and gives off a vinegary odor. It is highly lipid soluble and slightly soluble in water.
Clinical studies
ESPS2 (European Stroke Prevention Study-2) was a double-blind, placebo-controlled, 24-month study in which 6602 patients over the age of 18 years had an ischemic stroke (76%) or transient ischemic attack (TIA, 24%) within three months prior to entry. Patients were enrolled in 13 European countries between February 1989 and May 1995 and were randomized to one of four treatment groups: Aggrenox (aspirin/extended-release dipyridamole) 25 mg/200 mg; extended-release dipyridamole (ER-DP) 200 mg alone; aspirin (ASA) 25 mg alone; or placebo. The mean age in this population was 66.7 years with 58% of them being males. Patients received one capsule twice daily (morning and evening). Efficacy assessments included analyses of stroke (fatal or nonfatal) and death (from all causes) as confirmed by a blinded morbidity and mortality assessment group. There were no differences with regard to efficacy based on age or gender; patients who were older had a trend towards more events.
Stroke Endpoint
Aggrenox reduced the risk of stroke by 22.1% compared to aspirin 50 mg/day alone (p = 0.008) and reduced the risk of stroke by 24.4% compared to extended-release dipyridamole 400 mg/day alone (p = 0.002) (Table 3). Aggrenox reduced the risk of stroke by 36.8% compared to placebo (p <0.001).
Total Number of Patients n | Number of Patients With Stroke Within 2 Years n (%) | Kaplan-Meier Estimate of Survival at 2 Years (95% C.I.) | Gehan-Wilcoxon Test P-value | Risk Reduction at 2 Years | Odds Ratio (95% C.I.) | |
---|---|---|---|---|---|---|
a0.010 <p‑value ≤0.050; bp‑value ≤0.010. | ||||||
Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dosage regimen for all treatment groups is BID. | ||||||
Individual Treatment Group | ||||||
Aggrenox | 1650 | 157 ( 9.5%) | 89.9% (88.4%, 91.4%) | - | - | - |
ER-DP | 1654 | 211 (12.8%) | 86.7% (85.0%, 88.4%) | - | - | - |
ASA | 1649 | 206 (12.5%) | 87.1% (85.4%, 88.7%) | - | - | - |
Placebo | 1649 | 250 (15.2%) | 84.1% (82.2%, 85.9%) | - | - | - |
Pairwise Treatment Group Comparisons | ||||||
Aggrenox vs. ER-DP | - | - | - | 0.002b | 24.4% | 0.72 (0.58, 0.90) |
Aggrenox vs. ASA | - | - | - | 0.008b | 22.1% | 0.74 (0.59, 0.92) |
Aggrenox vs. Placebo | - | - | - | <0.001b | 36.8% | 0.59 (0.48, 0.73) |
ER-DP vs. Placebo | - | - | - | 0.036a | 16.5% | 0.82 (0.67, 1.00) |
ASA vs. Placebo | - | - | - | 0.009b | 18.9% | 0.80 (0.66, 0.97) |
ESPS2: Cumulative Stroke Rate (Fatal or Nonfatal)
Over 24 months of Follow-UP
Combined Stroke or Death Endpoint
In ESPS2, Aggrenox reduced the risk of stroke or death by 12.1% compared to aspirin alone and by 10.3% compared to extended-release dipyridamole alone. These results were not statistically significant. Aggrenox reduced the risk of stroke or death by 24.2% compared to placebo.
Death Endpoint
The incidence rate of all-cause mortality was 11.3% for Aggrenox, 11.0% for aspirin alone, 11.4% for extended-release dipyridamole alone and 12.3% for placebo alone. The differences between the Aggrenox, aspirin alone and extended-release dipyridamole alone treatment groups were not statistically significant. These incidence rates for Aggrenox and aspirin alone are consistent with previous aspirin studies in stroke and TIA patients.
Patient counseling information
Advise the patient to read the FDA-approved patient labeling (Patient Information).
- Risk of Bleeding
Inform patients that as with other antiplatelet agents, there is a general risk of bleeding including intracranial and gastrointestinal bleeding. Inform patients about the signs and symptoms of bleeding, including occult bleeding. Tell patients to notify their physician if they are prescribed any drug which may increase risk of bleeding.
Counsel patients who consume three or more alcoholic drinks daily about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin. - Pregnancy
Inform patients that aspirin is known to be harmful to fetuses and ask the patient to notify them if they are or become pregnant. - Headaches
Some patients may experience headaches upon treatment initiation; these are usually transient. In case of intolerable headaches, tell patients to contact their physician. - Dosage and Administration
Tell patients that Aggrenox capsules should be swallowed whole, and not chewed or crushed. If you miss a dose, continue with your next dose on your regular schedule. Do not take a double dose. - Storage
Inform patients to protect Aggrenox from moisture.
Distributed by:
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Licensed from:
Boehringer Ingelheim International GmbH
Copyright © 2015 Boehringer Ingelheim International GmbH
ALL RIGHTS RESERVED
OT1000MK132015
302420-02
Patient Information
Aggrenox® (AG-reh-nox)
(aspirin/extended-release dipyridamole)
Capsules
Read this Patient Information before you start taking Aggrenox and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is Aggrenox?
Aggrenox is a prescription medicine that contains aspirin and a medicine that is slowly released in your body, called dipyridamole. Aggrenox is used to lower the risk of stroke in people who have had a "mini-stroke" (transient ischemic attack or TIA) or stroke due to a blood clot.
It is not known if Aggrenox is safe and effective in children. See "Who should not take Aggrenox?"
Who should not take Aggrenox?
Do not take Aggrenox if you:
- are allergic to any of the ingredients in Aggrenox. See the end of this leaflet for a list of ingredients in Aggrenox.
- are allergic to non-steroidal anti-inflammatory drugs (NSAIDs)
- have asthma in combination with runny nose and nasal polyps
Do not give Aggrenox to a child or teenager with a viral illness. Reye syndrome, a life-threatening condition, can happen when aspirin (an ingredient in Aggrenox) is used in children and teenagers who have certain viral illnesses.
What should I tell my doctor before using Aggrenox?
Before taking Aggrenox, tell your healthcare provider if you:
- have stomach ulcers
- have a history of bleeding problems
- have heart problems
- have kidney or liver problems
- have low blood pressure
- have myasthenia gravis
- have any other medical conditions
- are pregnant or plan to become pregnant. Aggrenox can harm your unborn baby, especially if you take it in the last (third) trimester of pregnancy. You should not take Aggrenox during pregnancy without first talking to your healthcare provider. Tell your healthcare provider right away if you become pregnant while taking Aggrenox.
- are breast-feeding or plan to breast-feed. Aggrenox can pass into your milk and may harm your baby. Talk to your healthcare provider about the best way to feed your baby if you take Aggrenox.
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Aggrenox and other medicines may affect each other causing side effects. Aggrenox may affect the way other medicines work, and other medicines may affect how Aggrenox works.
Especially tell your healthcare provider if you take:
- a medicine for high blood pressure, irregular heart beat, or heart failure
- acetazolamide [Diamox®]
- any blood thinner medicines
- warfarin sodium [Coumadin®, Jantoven®]
- a heparin medicine
- anagrelide [Agrylin®]
- a seizure medicine
- a medicine for Alzheimer’s disease
- a water pill
- methotrexate sodium [Trexall®]
- aspirin or a non-steroidal anti-inflammatory drug (NSAIDs). You should not take NSAIDs during treatment with Aggrenox. Using these medicines with Aggrenox can increase your risk of bleeding.
- a medicine for diabetes
- probenecid [Probalan®, Col-Probenecid®]
Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above.
Know the medicines you take. Keep a list of them and show your healthcare provider and pharmacist when you get a new medicine.
How should I take Aggrenox?
- Take Aggrenox exactly as prescribed. Your healthcare provider will tell you how many Aggrenox to take and when to take them.
- Headaches are not uncommon when you first start taking Aggrenox, but often lessen as treatment continues. Tell your healthcare provider if you have a severe headache. Your healthcare provider may change the instructions for taking Aggrenox.
- Swallow Aggrenox whole. Do not crush or chew the capsules.
- You can take Aggrenox with or without food.
- If you miss a dose, take your next dose at the usual time. Do not take two doses at one time.
- If you take more Aggrenox (overdose) than prescribed, call your healthcare provider or Poison Control Center, or get emergency help right away.
Symptoms of an overdose of Aggrenox include:
- a warm feeling or flushing
- sweating
- restlessness
- weakness or dizziness
- a fast heart rate
- ringing in the ears
What should I avoid while using Aggrenox?
- heavy alcohol use. People who drink three or more alcoholic drinks every day have a higher risk of bleeding during treatment with Aggrenox, because it contains aspirin.
What are the possible side effects of Aggrenox?
Aggrenox may cause serious side effects, including:
- increased risk of bleeding. You may bleed more easily during Aggrenox treatment, and it may take longer than usual for bleeding to stop. This can include:
- bleeding into your brain (intracranial hemorrhage). This can be a medical emergency. Get medical help right away if you have any of these symptoms while taking Aggrenox:
- severe headache with drowsiness
- confusion or memory change
- pass out (become unconscious)
- bleeding in your stomach or intestine.
- stomach pain
- heartburn or nausea
- vomiting blood or vomit looks like "coffee grounds"
- red or bloody stools
- black stools that look like tar
- bleeding into your brain (intracranial hemorrhage). This can be a medical emergency. Get medical help right away if you have any of these symptoms while taking Aggrenox:
- new or worsening chest pain in some people with heart disease. Tell your healthcare provider if you have new chest pain or have any change in your chest pain during treatment with Aggrenox.
- liver problems, including increased liver function tests and liver failure. Tell your healthcare provider if you have any of these symptoms of a liver problem while taking Aggrenox:
- loss of appetite
- pale colored stool
- stomach area (abdomen) pain
- yellowing of your skin or whites of your eyes
- dark urine
- itching
Call your healthcare provider right away if you have any of the symptoms listed above.
The most common side effects of Aggrenox include:
- headache
- upset stomach
- diarrhea
These are not all the possible side effects of Aggrenox. Tell your healthcare provider or pharmacist if you have any side effect that bothers you or that does not go away.
Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Aggrenox?
- Store Aggrenox at 59°F to 86°F (15°C to 30°C).
- Keep Aggrenox capsules dry.
- Safely throw away medicine that is out of date or no longer needed.
Keep Aggrenox and all medicines out of the reach of children.
General information about Aggrenox
Medicines are sometimes prescribed for purposes other than those listed in the Patient Information. Do not use Aggrenox for a condition for which it was not prescribed. Do not give Aggrenox to other people, even if they have the same symptoms that you have. It may harm them.
This Patient Information summarizes the most important information about Aggrenox. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Aggrenox that is written for health professionals.
For more information, go to www.Aggrenox.com, scan the code below or call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257 or (TTY) 1-800-459-9906.
What are the ingredients in Aggrenox?
Active Ingredients: dipyridamole in an extended-release form and aspirin
Inactive Ingredients: acacia, aluminum stearate, colloidal silicon dioxide, corn starch, dimethicone, hypromellose, hypromellose phthalate, lactose monohydrate, methacrylic acid copolymer, microcrystalline cellulose, povidone, stearic acid, sucrose, talc, tartaric acid, titanium dioxide and triacetin. Each capsule shell contains gelatin, red iron oxide and yellow iron oxide, titanium dioxide, and water.
Distributed by:
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Licensed from:
Boehringer Ingelheim International GmbH
Copyright © 2015 Boehringer Ingelheim International GmbH
ALL RIGHTS RESERVED
Revised: November 2015
OT1000MK132015
302420-02
Aggrenox
(60) 25 mg/200 mg Capsules
NDC: 0597-0001-60
Aggrenox aspirin and dipyridamole capsule, extended release | |||||||||||||||||||
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Labeler - Boehringer Ingelheim Pharmaceuticals, Inc. (603175944) |
Registrant - Boehringer Ingelheim Pharmaceuticals, Inc. (603175944) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Polpharma S.A. | 422195139 | API MANUFACTURE(0597-0001) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Boehringer Ingelheim Espana, SA | 460940841 | API MANUFACTURE(0597-0001) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Boehringer Ingelheim Pharma GmbH and Co. KG | 340700520 | MANUFACTURE(0597-0001), ANALYSIS(0597-0001) |
Establishment | |||
Name | Address | ID/FEI | Operations |
Novacyl | 383661402 | API MANUFACTURE(0597-0001) |
Dosing & Uses
Dosage Forms & Strengths
aspirin/dipyridamole
capsule, extended release
- 25mg/200mg
Stroke
Secondary prophylaxis of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
1 capsule PO q12hr
Dosing considerations
- Not interchangeable with individual components of aspirin/dipyridamole
- Intolerable headaches during initial treatment: Switch to 1 capsule PO at bedtime; patient should return to normal regimen when possible (usually 1 week)
Dosing Modifications
GFR <10 mL/min: Use not recommended
Administration
Swallow capsules whole, without chewing
Safety and efficacy not established
Patient Handout
What is aspirin and dipyridamole (aggrenox)?
Aspirin is in a group of drugs called salicylates (sa-LIS-il-ates). It works by reducing substances in the body that cause pain, fever, and inflammation.
Dipyridamole keeps platelets in your blood from sticking together to form clots.
The combination of aspirin and dipyridamole is used to reduce the risk of stroke in people who have had blood clots or a "mini-stroke" (also called a transient ischemic attack or TIA).
Aspirin and dipyridamole may also be used for other purposes not listed in this medication guide.
What happens if i miss a dose (aggrenox)?
Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.
What is Aggrenox?
Aggrenox contains a combination of aspirin and dipyridamole. Aspirin belongs to a group of drugs called salicylates (sa-LIS-il-ates). It works by reducing substances in the body that cause pain, fever, and inflammation.
Dipyridamole keeps platelets in your blood from sticking together to form clots.
Aggrenox is used to reduce the risk of stroke in people who have had blood clots or a "mini-stroke" (also called a transient ischemic attack or TIA).
Aggrenox is supplied as a capsule containing 200mg dipyridamole in extended-release pellets and a round white tablet incorporating immediate-release aspirin 25mg.
Aspirin / dipyridamole Breastfeeding Warnings
US: Use should be avoided. UK: Benefit should outweigh risk. AU: Caution is recommended. Excreted into human milk: Yes (aspirin, dipyridamole) Comments: According to some experts, low-dose aspirin (75 to 162 mg daily) may be considered for antiplatelet therapy in breastfeeding women. Avoiding breastfeeding for 1 to 2 hours following a low dose of aspirin may minimize the risk of antiplatelet effects in the infant.