aspirin/dipyridamole (Rx)

>10%

Headache (10-39%)

Dyspepsia (4-18%)

Abdominal pain (4-18%)

Nausea (6-16%)

Diarrhea (13%)

1-10%

Vomiting (3-8%)

Pain (6%)

Fatigue (6%)

Arthralgia (5%)

Back pain (5%)

Hemorrhage, nonspecific (3%)

Accidental injury (3%)

Epistaxis (3%)

Amnesia (3%)

Arthritis (2%)

Melena (2%)

Asthenia (2%)

Convulsions (2%)

Neoplasm, nonspecific (2%)

Anemia (2%)

Rectal hemorrhage (2%)

Malaise (2%)

Cardiac failure (2%)

Coughing (2%)

Purpura (1%)

GI hemorrhage (1%)

Anorexia (1%)

Somnolence (1%)

Myalgia (1%)

Arthrosis (1%)

Confusion (1%)

Hemorrhoids (1%)

Syncope (1%)

Upper respiratory tract infection (1%)

Postmarketing Reports

Body as whole: Hypothermia, chest pain

Cardiovascular: Angina pectoris, tachycardia, palpitation

CNS: Cerebral edema, dizziness, cerebral hemorrhage, intracranial hemorrhage, subarachnoid hemorrhage

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

Psychiatric Disorders: Confusion, agitation

GI: Pancreatitis, Reye syndrome, hematemesis, gastritis, ulceration and perforation, hemorrhage rectum, melena, GI hemorrhage

General: Hearing loss, anorexia, migraine

Immune: Hypersensitivity, acute anaphylaxis, laryngeal edema

Hepatic: Hepatitis, hepatic failure, cholelithiasis, jaundice, hepatic function abnormal

Musculoskeletal: Rhabdomyolysis

Metabolic: Hypoglycemia, dehydration

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

Respiratory: Tachypnea, dyspnea

Skin: Rash, alopecia, angioedema, Stevens-Johnson syndrome, skin hemorrhage (eg, bruising, ecchymosis, hematoma), pruritus, urticaria

Urogenital: Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, hematuria

Platelet, bleeding and clotting disorders: Hematoma, gingival bleeding, epistaxis, purpura, aplastic anemia, pancytopenia, thrombocytosis, allergic vasculitis, prothrombin time (PT) prolongation, disseminated intravascular coagulation (DIC), coagulopathy, thrombocytopenia

Vascular (Extracardiac) Disorders:Flushing

Contraindications

Hypersensitivity to aspirin, dipyridamole, or NSAIDs

Syndrome of asthma, rhinitis, and nasal polyps

Children younger than 16 years with viral infections (risk of Reye syndrome)

Cautions

Discontinue if tinnitus or impaired hearing occurs

Use with caution in patients with cardiovascular or GI diseases or bleeding disorders

Risk of precipitation of chest pain in patients with underlying coronary artery disease (CAD)

Dosage in drug may not be adequate in patients with history of stroke or TIA for whom aspirin is indicated to prevent recurrent MI or angina pectoris

Preexisting hypotension may be exacerbated by peripheral vasodilation

Increased bleeding risk when drug coadministered with antiplatelet agents (eg, anagrelide), anticoagulants (eg, heparin), fibrinolytic agents, or NSAIDs (in long-term use)

When possible, surgical patients should not receive aspirin 2 weeks before undergoing a surgical procedure

Increased bleeding risk with chronic heavy alcohol use (>3 alcoholic drinks/day)

Risk of elevated liver function test values or hepatic failure with dipyridamole administration

Intake of drug within 48 hours prior to stress testing with intravenous dipyridamole or other adenosinergic agents may increase risk for cardiovascular side effects of and may impair sensitivity of test

Pregnancy

Available data from published studies and postmarketing experience with use during pregnancy have not identified clear association between drug use and major birth defects, miscarriage, or adverse maternal or fetal outcomes drug combination contains low-dose aspirin which is an NSAID

Increases risk for bleeding; maternal use of high-dose aspirin can result in excessive blood loss at delivery, prolonged gestation, prolonged labor, intracranial hemorrhage in premature infants, low birth weight, stillbirth, and neonatal death

Animal data

• In animal reproduction studies, there were adverse developmental effects with administration of aspirin in rats and rabbits at doses about 66 and 44 times, respectively, the human exposure at maximum recommended daily dose; reproduction studies with dipyridamole in mice, rabbits, and rats have revealed no evidence of harm to fetus up to doses about 25 times maximum recommended daily human dose; nonclinical data are suggestive of possible potentiation of aspirin-related fetal toxicity when combined with dipyridamole

Lactation

Based on data from a clinical lactation study in breastfeeding women taking low-dose aspirin, the metabolite salicylic acid is present in human milk in low levels; dipyridamole is also present in human milk; there is no information on the effects of drug combination components on breastfed infant or on milk production; there is insufficient information to determine effects of aspirin on breastfed infant and no information on effects of aspirin on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Aspirin: Inhibits platelet cyclooxygenase and thus inhibits generation of thromboxane A2, a powerful inducer of platelet aggregation and vasoconstriction, leading to abrogation of platelet aggregation

Dipyridamole: Inhibits uptake of adenosine into platelets, endothelial cells, and erythrocytes

Combination of aspirin and dipyridamole produces additive antiplatelet effects

Absorption

Peak plasma levels: Dipyridamole, 2 hr

Distribution

Protein bound: Dipyridamole, 99%

Vd: Dipyridamole, 92 L

Metabolism

Metabolized by liver: Dipyridamole

Elimination

Dipyridamole: Feces (95%), urine (5%)