aspirin and dipyridamole

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.

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 )] • The most frequently reported adverse reactions (>10% and greater than placebo) were headache, dyspepsia, abdominal pain, nausea, and diarrhea ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar RxLLC at 1-800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 aspirin and extended-release dipyridamole capsules was established in the European Stroke Prevention Study-2 (ESPS2). ESPS2 was a double-blind, placebo-controlled study that evaluated 6,602 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 aspirin and extended-release dipyridamole capsules, aspirin, ER-DP, or placebo [see Clinical Studies (14)]; primary endpoints included stroke (fatal or nonfatal) and death from all causes. This 24-month,…

Hypersensitivity to any product ingredients ( 4.1 ) • Patients with known allergy to NSAIDs ( 4.2 ) • Patients with the syndrome of asthma, rhinitis, and nasal polyps ( 4.2 ) 4.1 Hypersensitivity Aspirin and extended-release dipyridamole capsules are contraindicated in patients with known hypersensitivity to any of the product components. 4.2 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. 4.3 Reye Syndrome Do not use aspirin in children or teenagers with viral infections because of the risk of Reye syndrome.

Because of the dose ratio of dipyridamole to aspirin, overdosage of aspirin and extended-release dipyridamole capsules are 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 mg/mL. In severe cases, hyperthermia and hypovolemia are the major immediate threats to life. Plasma concentrations of aspirin above 300 mg/mL are clearly toxic. Severe toxic effects are associated with levels above 400 mg/mL. A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 grams. Treatment of overdose consists primarily of supporting vital functions, increasing drug elimination, and correcting acid-base disturbances. Consider gastric emptying…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Co-administration with anticoagulants, antiplatelets, or NSAIDs can increase risk of bleeding ( 7.1 ) • Decreased renal function can occur with co-administration with NSAIDs ( 7.1 ) 7.1 Drug Interaction Study Information Obtained From Literature Adenosinergic agents (e.g. adenosine, regadenoson) Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Dipyridamole also increases the cardiovascular effects of regadenoson, an adenosine A 2A -receptor agonist. The potential risk of cardiovascular side effects with intravenous adenosinergic agents may be increased during the testing period when dipyridamole is not held 48 hours prior to stress testing. Angiotensin Converting Enzyme (ACE) Inhibitors Because of 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. Anticoagulants and Antiplatelets Patients taking aspirin and extended-release dipyridamole capsules in combination with anticoagulants, antiplatelets, or any substance impacting coagulation are at increased risk for bleeding. 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. Anagrelide Patients taking aspirin in combination with anagrelide are at an increased risk of bleeding. 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.