Antiplatelet Agent

Reduction in the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis

B (dipyridamole); D (aspirin)

Aggrenox™ should be used in pregnancy only if the benefit justifies the potential risk to the fetus. It should not be used in the third trimester of pregnancy.

Hypersensitivity to dipyridamole, aspirin, or any component; allergy to NSAIDs; patients with asthma, rhinitis, and nasal polyps; bleeding disorders (factor VII or IX deficiencies); children <16 years of age with viral infections; pregnancy (especially 3rd trimester)

Patients who consume greater than or equal to 3 alcoholic drinks per day are at risk of bleeding. Cautious use in patients with inherited or acquired bleeding disorders including those of liver disease or vitamin K deficiency. Watch for signs and symptoms of GI ulcers and bleeding. Avoid use in patients with active peptic ulcer disease. Discontinue use if dizziness, tinnitus, or impaired hearing occurs. Stop 1-2 weeks before elective surgical procedures to avoid bleeding. Use caution in the elderly who are at high risk for adverse events. Cautious use in patients with hypotension, patients with unstable angina, recent MI, and hepatic dysfunction. Avoid in patients with severe renal failure. Safety and efficacy in children have not been established.

>10%:

Central nervous system: Headache (38.2%)

Gastrointestinal: Dyspepsia, abdominal pain (17.5%), nausea (16%), diarrhea (12.7%)

1% to 10%:

Central nervous system: Pain (6.4%), seizures (1.7%), fatigue (5.8%), malaise (1.6%), syncope (1%), amnesia (2.4%), confusion (1.1%), somnolence (1.2%)

Cardiovascular: Cardiac failure (1.6%)

Dermatologic: Purpura (1.4%)

Gastrointestinal: Vomiting (8.4%), bleeding (4.1%), rectal bleeding 1.6%, hemorrhoids (1%), hemorrhage 1.2%, anorexia (1.2%)

Hematologic: Anemia (1.6%)

Neuromuscular & skeletal: Back pain (4.6%), weakness (1.8%), arthralgia (5.5%), arthritis (2.1%), arthrosis (1.1%), myalgia (1.2%)

Respiratory: Cough (1.5%), upper respiratory tract infections (1%), epistaxis (2.4%)

<1% (limited to life-threatening or important symptoms): Intracranial hemorrhage (0.6%), allergic reaction, fever, hypotension, coma, dizziness, paresthesia, cerebral hemorrhage, subarachnoid hemorrhage, gastritis, ulceration, perforation, tinnitus, deafness, tachycardia, palpitations, arrhythmia, supraventricular tachycardia, cholelithiasis, jaundice, hepatic function abnormality, hyperglycemia, thirst, hematoma, gingival bleeding, agitation, uterine hemorrhage, hyperpnea, asthma, bronchospasm, hemoptysis, pulmonary edema, taste loss, pruritus, urticaria, renal insufficiency and failure, hematuria, flushing, hypothermia, chest pain, angina pectoris, cerebral edema, pancreatitis, Reye's syndrome, hematemesis, hearing impairment, anaphylaxis, laryngeal edema, hepatitis, hepatic failure, rhabdomyolysis, hypoglycemia, dehydration, prolonged PT time, disseminated intravascular coagulation, coagulopathy, thrombocytopenia, prolonged pregnancy and labor, stillbirths, lower weight infants, antepartum and postpartum bleeding, tachypnea, dyspnea, rash, alopecia, angioedema, Stevens-Johnson syndrome, interstitial nephritis, papillary necrosis, proteinuria, allergic vasculitis, anemia (aplastic), pancytopenia, thrombocytosis

Symptoms of dipyridamole overdose might predominate because of the ratio of dipyridamole to aspirin. Symptoms may include hypotension and peripheral vasodilation. Treatment would include I.V. fluids and possibly vasopressors. Careful medical management is necessary.

Increased effects: Plasma levels and cardiovascular effects of adenosine are increased; decrease adenosine dose. Use of aspirin-dipyridamole with anticoagulants (heparin, low molecular weight heparins, warfarin) or antiplatelet agents (NSAIDs, IIb/IIIa antagonists) may increase the risk of bleeding. Serum concentrations and and toxicity of methotrexate may be increased when used concurrently with aspirin; avoid concurrent use. Serum concentrations of acetazolamide, phenytoin or valproic acid may be increased with aspirin. Concurrent use of verapamil may prolong bleeding times.

Decreased effect: Angiotensin-converting enzyme inhibitors may have diminished pharmacologic effect with aspirin (at higher dosages). The effect of cholinesterase inhibitors may be reduced with concurrent aspirin-dipyridamole therapy; avoid concurrent use. Aspirin may diminish the effect of diuretics, probenecid, and sulfinpyrazone.

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); protect from excessive moisture

The antithrombotic action results from additive antiplatelet effects. Dipyridamole inhibits the uptake of adenosine into platelets, endothelial cells, and erythrocytes. Aspirin inhibits platelet aggregation by irreversible inhibition of platelet cyclo-oxygenase and thus inhibits the generation of thromboxane A2.

Peak effect: Peak plasma concentration (steady-state): Dipyridamole: 1.9 mg/mL; aspirin: 319 ng/mL

Distribution: V_d: Dipyridamole: 92 L; aspirin: 10 L

Protein binding: Dipyridamole: 99%

Metabolism: Dipyridamole is metabolized hepatically by conjugation with glucuronic acid. Aspirin undergoes hydrolysis to salicylic acid in the liver and gastrointestinal wall. Metabolism of salicylic acid occurs primarily by conjugation in the liver; metabolic pathways are saturable.

Bioavailability: 50% to 75% of aspirin dose reaches systemic circulation as aspirin

Half-life: Dipyridamole: 13.6 hours; salicylic acid: 1.71 hours

Time to peak: Dipyridamole: 2 hours; aspirin: 0.63 hours

Elimination: Ninety-five percent of dipyridamole's glucuronide metabolite is excreted via the bile into the feces. Five percent is excreted in the urine. Following therapeutic doses of aspirin, about 10% is excreted as salicylic acid and 75% as salicyluric acid in the urine.

Adults: Oral: 1 capsule (200 mg dipyridamole, 25 mg aspirin) twice daily.

Dosage adjustment in hepatic impairment: Avoid use in patients with severe hepatic impairment; studies have not been done in patients with varying degrees of hepatic impairment

Elderly: Plasma concentrations were 40% higher, but specific dosage adjustments have not been recommended

Hemoglobin, hematocrit, signs or symptoms of bleeding, signs or symptoms of stroke

No information available to require special precautions

No effects or complications reported

Swallow capsule whole without chewing or crushing; monitor for signs and symptoms of bleeding or another stroke or transient ischemic attack

Monitor for signs and symptoms of bleeding or another stroke or transient ischemic attack

Capsule: 200 mg dipyridamole, 25 mg aspirin