Drug: Aggrenox

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:
C24H40N8O4   ......    Mol. Wt. 504.63 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: a
C9H8O4    ......   Mol. Wt. 180.16 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.

Source: http://www.rxlist.com

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*
Body System/Preferred Term Individual Treatment Group AGGRENOX ER-DP Alone ASA Alone Placebo 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%) * 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. 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 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%) Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dosage regimen for all treatment groups is BID 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 Aggrenox (aspirin, extended-release dipyridamole capsules) Side Effects Center for a complete guide to possible side effectsLearn More »

Source: http://www.rxlist.com

AGGRENOX is not interchangeable with the individual components of aspirin and dipyridamole tablets. The recommended dose of AGGRENOX is one capsule given orally twice daily, one in the morning and one in the evening. Swallow capsules whole without chewing. AGGRENOX can be administered with or without food. Alternative Regimen in Case of Intolerable Headaches In the event of intolerable headaches during initial treatment, switch to one capsule at bedtime and low-dose aspirin in the morning. Because there are no outcome data with this regimen and headaches become less of a problem as treatment continues, patients should return to the usual regimen as soon as possible, usually within one week.

Source: http://www.rxlist.com

No pharmacokinetic drug-drug interaction studies were conducted with AGGRENOX capsules. The following information was obtained from the literature. Adenosine Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Angiotensin Converting Enzyme (ACE) Inhibitors Due to the indirect effect of aspirin on the renin-angiotensin conversion pathway, the hyponatremic and hypotensive effects of ACE inhibitors may be diminished by concomitant administration of aspirin. Acetazolamide Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide (and toxicity) due to competition at the renal tubule for secretion. Anticoagulant Therapy (heparin and warfarin) Patients on anticoagulation therapy are at increased risk for bleeding because of drug-drug interactions and effects on platelets. Aspirin can displace warfarin from protein binding sites, leading to prolongation of both the prothrombin time and the bleeding time. Aspirin can increase the anticoagulant activity of heparin, increasing bleeding risk. Anticonvulsants Salicylic acid can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels. Beta Blockers The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. Cholinesterase Inhibitors Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors, thereby potentially aggravating myasthenia gravis. Diuretics The effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. Methotrexate Salicylate can inhibit renal clearance of methotrexate, leading to bone marrow toxicity, especially in the elderly or renal impaired. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) The concurrent use of aspirin with other NSAIDs may increase bleeding or lead to decreased renal function. Oral Hypoglycemics Moderate doses of aspirin may increase the effectiveness of oral hypoglycemic drugs, leading to hypoglycemia. Uricosuric Agents (probenecid and sulfinpyrazone) Salicylates antagonize the uricosuric action of uricosuric agents. Read the Aggrenox Drug Interactions Center for a complete guide to possible interactions Learn More »

Source: http://www.rxlist.com

AGGRENOX is indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis.

Source: http://www.rxlist.com

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 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. Last reviewed on RxList: 9/14/2012
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Because of the dose ratio of dipyridamole to aspirin, overdosage of AGGRENOX is likely to be dominated by signs and symptoms of dipyridamole overdose. In case of real or suspected overdose, seek medical attention or contact a Poison Control Center immediately. Careful medical management is essential. Based upon the known hemodynamic effects of dipyridamole, symptoms such as warm feeling, flushes, sweating, restlessness, feeling of weakness and dizziness may occur. A drop in blood pressure and tachycardia might also be observed. Salicylate toxicity may result from acute ingestion (overdose) or chronic intoxication. Severity of aspirin intoxication is determined by measuring the blood salicylate level. The early signs of salicylic overdose (salicylism), including tinnitus (ringing in the ears), occur at plasma concentrations approaching 200 μg/mL. In severe cases, hyperthermia and hypovolemia are the major immediate threats to life. Plasma concentrations of aspirin above 300 μg/mL are clearly toxic. Severe toxic effects are associated with levels above 400 μg/mL. A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 g. Treatment of overdose consists primarily of supporting vital functions, increasing drug elimination, and correcting acid-base disturbances. Consider gastric emptying and/or lavage as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of activated charcoal as a slurry may be beneficial if less than 3 hours have passed since ingestion. Charcoal absorption should not be employed prior to emesis and lavage. Follow acid-base status closely with serial blood gas and serum pH measurements. Maintain fluid and electrolyte balance. Administer replacement fluid intravenously and augment with correction of acidosis. Treatment may require the use of a vasopressor. Infusion of glucose may be required to control hypoglycemia. Administration of xanthine derivatives (e.g., aminophylline) may reverse the hemodynamic effects of dipyridamole overdose. Plasma electrolytes and pH should be monitored serially to promote alkaline diuresis of salicylate if renal function is normal. In patients with renal insufficiency or in cases of life-threatening intoxication, dialysis is usually required to treat salicylic overdose, however since dipyridamole is highly protein bound, dialysis is not likely to remove dipyridamole. Exchange transfusion may be indicated in infants and young children.

Source: http://www.rxlist.com

Dosage Forms And Strengths 25 mg/200 mg capsules with a red cap and an ivory-colored body, containing yellow extended-release pellets incorporating dipyridamole and a round white tablet incorporating immediate-release aspirin. The capsule body is imprinted in red with the Boehringer Ingelheim logo and with “01A”. Storage And Handling AGGRENOX capsules are available as a hard gelatin capsule, with a red cap and an ivory-colored body, containing yellow extended-release pellets incorporating dipyridamole and a round white tablet incorporating immediate-release aspirin. The capsule body is imprinted in red with the Boehringer Ingelheim logo and with “01A”. AGGRENOX capsules are supplied in unit-of-use bottles of 60 capsules (NDC 0597-0001-60). Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from excessive moisture. Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877 USA. Revised: 1/2011 Last reviewed on RxList: 9/14/2012
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Risk of Bleeding Intracranial Hemorrhage In ESPS2 the incidence of intracranial hemorrhage was 0.6% in the AGGRENOX group, 0.5% in the extended-release dipyridamole (ER-DP) group, 0.4% in the aspirin (ASA) group and 0.4% in the placebo groups. Coagulation Abnormalities Even low doses of aspirin can inhibit platelet function leading to an increase in bleeding time. This can adversely affect patients with inherited or acquired (liver disease or vitamin K deficiency) bleeding disorders [see DRUG INTERACTIONS]. Gastrointestinal (GI) Side Effects GI side effects include stomach pain, heartburn, nausea, vomiting, and gross GI bleeding. Although minor upper GI symptoms, such as dyspepsia, are common and can occur anytime during therapy, physicians should remain alert for signs of ulceration and bleeding, even in the absence of previous GI symptoms. Inform patients about the signs and symptoms of GI side effects and what steps to take if they occur. In ESPS2 the incidence of gastrointestinal bleeding was 4.1% in the AGGRENOX group, 2.2% in the extended-release dipyridamole group, 3.2% in the aspirin group, and 2.1% in the placebo groups. Peptic Ulcer Disease Avoid using aspirin in patients with a history of active peptic ulcer disease, which can cause gastric mucosal irritation and bleeding. Alcohol Warning Because AGGRENOX contains aspirin, counsel patients who consume three or more alcoholic drinks every day about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin. Renal Failure Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10 mL/minute) [see Use in Specific Populations and CLINICAL PHARMACOLOGY]. Hepatic Insufficiency Elevations of hepatic enzymes and hepatic failure have been reported in association with dipyridamole administration [see Use in Specific Populations and CLINICAL PHARMACOLOGY]. Pregnancy Because AGGRENOX contains aspirin, AGGRENOX can cause fetal harm when administered to a pregnant woman. Maternal aspirin use during later stages of pregnancy may cause low birth weight, increased incidence for intracranial hemorrhage in premature infants, stillbirths and neonatal death. Because of the above and because of the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system (closure of the ductus arteriosus), avoid AGGRENOX in the third trimester of pregnancy [see Use In Specific Populations]. Aspirin has been shown to be teratogenic in rats (spina bifida, exencephaly, microphthalmia and coelosomia) and rabbits (congested fetuses, agenesis of skull and upper jaw, generalized edema with malformation of the head, and diaphanous skin) at oral doses of 330 mg/kg/day and 110 mg/kg/day, respectively. These doses, which also resulted in a high resorption rate in rats (63% of implantations versus 5% in controls), are, on a mg/m² basis, about 66 and 44 times, respectively, the dose of aspirin contained in the maximum recommended daily human dose of AGGRENOX. Reproduction studies with dipyridamole have been performed in mice, rabbits and rats at oral doses of up to 125 mg/kg, 40 mg/kg and 1000 mg/kg, respectively (about 1½, 2 and 25 times the maximum recommended daily human oral dose, respectively, on a mg/m² basis) and have revealed no evidence of harm to the fetus due to dipyridamole. When 330 mg aspirin/kg/day was combined with 75 mg dipyridamole/kg/day in the rat, the resorption rate approached 100%, indicating potentiation of aspirin-related fetal toxicity. There are no adequate and well-controlled studies of the use of AGGRENOX in pregnant women. If AGGRENOX is used during pregnancy, or if the patient becomes pregnant while taking AGGRENOX, inform the patient of the potential hazard to the fetus. Coronary Artery Disease Dipyridamole has a vasodilatory effect. Chest pain may be precipitated or aggravated in patients with underlying coronary artery disease who are receiving dipyridamole. For stroke or TIA patients for whom aspirin is indicated to prevent recurrent myocardial infarction (MI) or angina pectoris, the aspirin in this product may not provide adequate treatment for the cardiac indications. Hypotension Dipyridamole produces peripheral vasodilation, which can exacerbate pre-existing hypotension. General AGGRENOX capsules are not interchangeable with the individual components of aspirin and dipyridamole tablets. Patient Counseling Information See FDA-approved Patient Labeling 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 the patient 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. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility In studies in which dipyridamole was administered in the feed to mice (up to 111 weeks in males and females) and rats (up to 128 weeks in males and up to 142 weeks in females), there was no evidence of drug-related carcinogenesis. The highest dose administered in these studies (75 mg/kg/day) was, on a mg/m² basis, about equivalent to the maximum recommended daily human oral dose (MRHD) in mice and about twice the MRHD in rats. Combinations of dipyridamole and aspirin (1:5 ratio) tested negative in the Ames test, in vivo chromosome aberration tests (in mice and hamsters), oral micronucleus tests (in mice and hamsters) and oral dominant lethal test (in mice). Aspirin, alone, induced chromosome aberrations in cultured human fibroblasts. Mutagenicity tests of dipyridamole alone with bacterial and mammalian cell systems were negative. Combinations of dipyridamole and aspirin have not been evaluated for effects on fertility and reproductive performance. There was no evidence of impaired fertility when dipyridamole was administered to male and female rats at oral doses up to 500 mg/kg/day (about 12 times the MRHD on a mg/m² basis). A significant reduction in number of corpora lutea with consequent reduction in implantations and live fetuses was, however, observed at 1250 mg/kg (more than 30 times the MRHD on a mg/m² basis). Aspirin inhibits ovulation in rats. Use In Specific Populations Pregnancy Teratogenic Effects, Pregnancy Category D. [see WARNINGS AND PRECAUTIONS]. Labor and Delivery Aspirin can result in excessive blood loss at delivery as well as prolonged gestation and prolonged labor. Because of these effects on the mother and because of adverse fetal effects seen with aspirin during the later stages of pregnancy [see WARNINGS AND PRECAUTIONS], avoid AGGRENOX in the third trimester of pregnancy and during labor and delivery. Nursing Mothers Both dipyridamole and aspirin are excreted in human milk. Exercise caution when AGGRENOX capsules are administered to a nursing woman. Pediatric Use Safety and effectiveness of AGGRENOX in pediatric patients have not been studied. Due to the aspirin component, use of this product in the pediatric population is not recommended [see CONTRAINDICATIONS]. Geriatric Use Of the total number of subjects in ESPS2, 61 percent were 65 and over, while 27 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see CLINICAL PHARMACOLOGY]. Patients with Severe Hepatic or Severe Renal Dysfunction AGGRENOX has not been studied in patients with hepatic or renal impairment. Avoid using aspirin containing products, such as Aggrenox in patients with severe hepatic or severe renal (glomerular filtration rate < 10 mL/min) dysfunction [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 9/14/2012
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Health Services in Toronto

Drug Database Online

Welcome to WebHealthNetwork an online drug guide and dictionary, here you can get drug information and definitaions for most popular pharmaceutical and medicinal drugs, and specifically Aggrenox. Find what medications you are taking today.