ASPRIN AND EXTENDED-RELEASE DIPYRIDAMOLE

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Aspirin and extended-release dipyridamole capsules are indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis. • Aspirin and extended-release dipyridamole capsules are a combination of aspirin and dipyridamole, antiplatelet agents, indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Aspirin and extended-release dipyridamole capsules are not interchangeable with the individual components of aspirin and dipyridamole tablets. The recommended dose of aspirin and extended-release dipyridamole capsules is one capsule given orally twice daily, one in the morning and one in the evening. Swallow capsules whole without chewing. Aspirin and extended-release dipyridamole capsules can be administered with or without food. • One capsule twice daily (morning and evening) with or without food ( 2 ) • In case of intolerable headaches during initial treatment, switch to one capsule at bedtime and low-dose aspirin in the morning; resume BID dosing within one week ( 2.1 ) • Do not chew capsule ( 2 ) • Not interchangeable with the individual components of aspirin and dipyridamole tablets ( 2 ) • Dispense in this unit-of-use container ( 16 ) 2.1 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. Warnings and cautions 5 WARNINGS AND PRECAUTIONS • Aspirin and extended-release dipyridamole capsules increase the risk of bleeding ( 5.1 ) • Avoid use in patients with severe hepatic or renal insufficiency ( 5.2 , 5.3 ) • Interrupt aspirin and extended-release dipyridamole capsules 48 hours before using intravenous dipyridamole or other adenosinergic agents for stress testing ( 5.6 , 7.1 ) 5.1 Risk of Bleeding Aspirin and extended-release dipyridamole capsules increase the risk of bleeding. Risk factors for bleeding include the use of other drugs that increase the risk of bleeding (e.g., anticoagulants, antiplatelet agents, heparin, anagrelide, fibrinolytic therapy, and chronic use of NSAIDs) [ see Drug Interaction (7.1) ]. Intracranial Hemorrhage In European Stroke Prevention Study-2 (ESPS2), the annualized event rate for intracranial hemorrhage was 0.39%/year in the Aspirin and extended-release dipyridamole capsules group, 0.26%/year in the extended-release dipyridamole (ER-DP) group, 0.24%/year in the aspirin (ASA) group, and 0.29%/year in the placebo groups. 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 annualized event rate for gastrointestinal bleeding was 2.97%/year in the Aspirin and extended-release dipyridamole capsules group, 1.58%/year in the extended-release dipyridamole group, 2.06%/year in the aspirin group, and 1.40%/year 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 aspirin and extended-release dipyridamole capsules contain 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. 5.2 Renal Failure Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10 mL/minute) [ see Use in specific Population ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ]. 5.3 Hepatic Insufficiency Elevations of hepatic enzymes and hepatic failure have been reported in association with dipyridamole administration [ see Use in specific Population ( 8.6 ) and Clinical Pharmacology ( 12.3 ) ]. 5.4 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. 5.5 Hypotension Dipyridamole produces peripheral vasodilation, which can exacerbate pre-existing hypotension. 5.6 Stress Testing with Intrav