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Aspirin and extended-release dipyridamole: Drug information

Aspirin and extended-release dipyridamole: Drug information
(For additional information see "Aspirin and extended-release dipyridamole: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Aggrenox [DSC]
Brand Names: Canada
  • Aggrenox [DSC];
  • TARO-Dipyridamole w/ ASA
Pharmacologic Category
  • Antiplatelet Agent
Dosing: Adult
Ischemic stroke or transient ischemic attack, noncardioembolic, secondary prevention

Ischemic stroke or transient ischemic attack, noncardioembolic, secondary prevention:

Note: In patients who receive IV thrombolytic therapy, antiplatelet therapy is generally delayed for at least 24 hours, but administered as soon as possible thereafter (Ref).

Oral: One capsule (aspirin 25 mg/dipyridamole ER 200 mg) twice daily. Note: If patient experiences intolerable headache during initial therapy, reduce dose to one capsule (aspirin 25 mg/dipyridamole ER 200 mg) at bedtime and low-dose aspirin in the morning. Return to usual dose (one capsule twice daily) as soon as tolerance to headache develops (usually within 1 week).

Carotid artery stenosis, symptomatic

Carotid artery stenosis, symptomatic (including recent carotid endarterectomy) (off-label use): Oral: One capsule (aspirin 25 mg/dipyridamole ER 200 mg) twice daily (Ref).

Hemodialysis graft patency

Hemodialysis graft patency (off-label use): Oral: One capsule (aspirin 25 mg/dipyridamole ER 200 mg) twice daily (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

GFR ≥10 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

GFR <10 mL/minute: Avoid use.

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Severe impairment: Avoid use.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Also see individual agents.

>10%:

Central nervous system: Headache (39%; tolerance usually develops)

Gastrointestinal: Abdominal pain (18%), dyspepsia (18%), nausea (16%), diarrhea (13%)

1% to 10%:

Gastrointestinal: Vomiting (8%), gastrointestinal hemorrhage (3%)

Hematologic & oncologic: Hemorrhage (3%)

<1%, postmarketing, and/or case reports: Agitation, alopecia, anaphylaxis, angina pectoris, angioedema, anorexia, aplastic anemia, bronchospasm, bruise, cardiac arrhythmia, cerebral edema, cerebral hemorrhage, chest pain, cholelithiasis, confusion, dehydration, disorder of hemostatic components of blood, disseminated intravascular coagulation, dizziness, dyspnea, ecchymoses, flushing, gastritis, gastrointestinal perforation, gastrointestinal ulcer, gingival hemorrhage, hearing loss, hematemesis, hematoma, hematuria, hemoptysis, hepatic failure, hepatic insufficiency, hepatitis, hyperkalemia, hypersensitivity angiitis, hypersensitivity reaction, hypoglycemia, hypokalemia, hypotension, hypothermia, interstitial nephritis, intracranial hemorrhage, jaundice, laryngeal edema, melena, metabolic acidosis, migraine, myalgia, nonthrombocytopenic purpura, palpitations, pancreatitis, pancytopenia, prolonged prothrombin time, proteinuria, pruritus, rectal hemorrhage, renal failure syndrome, renal insufficiency, renal papillary necrosis, respiratory alkalosis, Reye's syndrome, rhabdomyolysis, skin rash, Stevens-Johnson syndrome, subarachnoid hemorrhage, supraventricular tachycardia, syncope, tachycardia, tachypnea, thrombocythemia, thrombocytopenia, urticaria

Contraindications

Hypersensitivity to aspirin, dipyridamole, or any component of the formulation; allergy to nonsteroidal anti-inflammatory drugs (NSAIDs); patients with the syndrome of asthma, rhinitis, and nasal polyps; children or adolescents with viral infections.

Canadian labeling: Additional contraindications (not in US labeling): Patients with hereditary fructose and/or galactose intolerance; active GI ulcer or bleeding disorders; last trimester of pregnancy

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: Aspirin may increase the risk of bleeding; risk factors include the use of other drugs that increase the risk of bleeding (eg, anticoagulants, antiplatelet agents, heparin, fibrinolytic therapy, chronic use of nonsteroidal anti-inflammatory drugs). Use with caution in patients with acquired or inherited platelet and bleeding disorders; monitor for signs and symptoms of GI ulcers and bleeding. Use in active GI ulcer or bleeding disorders is contraindicated in the Canadian labeling.

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with nonsteroidal anti-inflammatory drugs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI effects: Stomach pain, heartburn, nausea, vomiting, and GI bleeding may occur. Avoid use in patients with a history of active peptic ulcer disease. Use with caution in patients with erosive gastritis or peptic ulcer disease.

• Hepatic effects: Elevated hepatic enzymes and hepatic failure have been reported with dipyridamole.

• Salicylate sensitivity: Patients with sensitivity to tartrazine dyes, nasal polyps, and asthma may have an increased risk of salicylate sensitivity.

• Tinnitus: Discontinue use if tinnitus or impaired hearing occurs.

Disease-related concerns:

• Cardiovascular disease: Dipyridamole produces peripheral vasodilation; may exacerbate preexisting hypotension and/or chest pain in patients with coronary artery disease. Use with caution in patients with hypotension, unstable angina, and/or recent myocardial infarction (MI); discontinue use 48 hours prior to pharmacologic (IV dipyridamole) stress testing. Note: Amount of aspirin provided may not be adequate for cardiac indications (eg, angina pectoris, MI prophylaxis).

• Ethanol use: Heavy ethanol use (>3 drinks/day) may increase bleeding risk and may enhance gastric mucosal irritation and bleeding.

• Hepatic impairment: Avoid use in severe hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment (GFR ≥10 mL/minute); avoid use in severe impairment (GFR <10 mL/minute).

Concurrent drug therapy issues:

• Pharmacologic stress testing: Interrupt therapy for 48 hours prior to stress testing with adenosine, IV dipyridamole, or regadenoson; may increase risk for cardiovascular adverse effects and impair the test sensitivity.

Special populations:

• Pediatric: Avoid use in children due to risk of Reye syndrome associated with aspirin component.

• Surgical patients: Aspirin should be avoided (if possible) in surgical patients for 1 to 2 weeks prior to surgery, to reduce the risk of excessive bleeding. Consider risk versus benefit when discontinuing prior to surgery.

Dosage form specific issues:

• Interchangeability: Aspirin/dipyridamole ER combination product is not interchangeable with the individual components of aspirin and dipyridamole.

• Lactose/sucrose: Formulation may contain lactose and/or sucrose; use in patients with fructose and/or galactose intolerance is contraindicated in the Canadian labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 12 Hour, Oral:

Aggrenox: Aspirin 25 mg [immediate release] and dipyridamole 200 mg [extended release] [DSC]

Generic: Aspirin 25 mg [immediate release] and dipyridamole 200 mg [extended release]

Generic Equivalent Available: US

Yes

Pricing: US

Capsule, 12-hour (Aspirin-Dipyridamole ER Oral)

25-200 mg (per each): $8.36 - $8.37

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 12 Hour, Oral:

Aggrenox: Aspirin 25 mg [immediate release] and dipyridamole 200 mg [extended release] [DSC]

Generic: Aspirin 25 mg [immediate release] and dipyridamole 200 mg [extended release]

Administration: Adult

Oral: Administer with or without food. Capsule should be swallowed whole; do not crush or chew.

Bariatric surgery: Capsule, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Cannot open capsule and cannot separate into its separate components on a same mg basis since aspirin is not available in that strength. Switch to a different antiplatelet medication.

Use: Labeled Indications

Ischemic stroke or transient ischemic attack, noncardioembolic, secondary prevention: Reduction in the risk of stroke in patients who have had transient ischemia of the brain or complete ischemic stroke due to thrombosis (AHA/ASA [Kleindorfer 2021]; manufacturer’s labeling).

Use: Off-Label: Adult

Carotid artery stenosis, symptomatic (including recent carotid endarterectomy); Hemodialysis graft patency

Medication Safety Issues
Sound-alike/look-alike issues:

Aggrenox may be confused with Aggrastat.

Pediatric patients: High-risk medication:

KIDs List: Salicylates, when used in pediatric patients <18 years of age with suspicion of viral illness (influenza, chickenpox), are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of Reye syndrome (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: Aspirin may enhance the antiplatelet effect of Abrocitinib. Management: Do not use aspirin at doses greater than 81 mg/day with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. Risk D: Consider therapy modification

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Acetylcholinesterase Inhibitors: Dipyridamole may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Adenosine: Dipyridamole may enhance the adverse/toxic effect of Adenosine. Specifically, cardiovascular effects of adenosine may be enhanced. Adenosine dose reduction may be needed. Management: For patients requiring pharmacologic stress testing with adenosine, hold dipyridamole tablets for 48 hours. Hold aspirin/dipyridamole capsules for 24 to 48 hours. For treatment of SVT, monitor for prolonged adenosine effects, consider lower initial doses. Risk D: Consider therapy modification

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Agents with Blood Glucose Lowering Effects: Salicylates may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Aspirin. Specifically, alcohol may increase the bleeding risk of aspirin. Alcohol (Ethyl) may diminish the therapeutic effect of Aspirin. Specifically, alcohol may interfere with the controlled release mechanism of extended release aspirin. Risk C: Monitor therapy

Alendronate: Aspirin may enhance the adverse/toxic effect of Alendronate. Specifically, the incidence of upper gastrointestinal adverse events may be increased Risk C: Monitor therapy

Ammonium Chloride: May increase the serum concentration of Salicylates. Risk C: Monitor therapy

Anagrelide: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Salicylates may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Apixaban: Aspirin may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk D: Consider therapy modification

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Risk C: Monitor therapy

Beta-Blockers: Dipyridamole may enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

Carbonic Anhydrase Inhibitors: Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Risk D: Consider therapy modification

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Cladribine: Inhibitors of Equilibrative Nucleoside (ENT1) and Concentrative Nucleoside (CNT3) Transport Proteins may increase the serum concentration of Cladribine. Management: Avoid concomitant use of ENT1 or CNT3 inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider an ENT1 or CNT3 inhibitor dose reduction and separation in the timing of administration. Risk D: Consider therapy modification

ClomiPRAMINE: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Collagenase (Systemic): Aspirin may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy

Corticosteroids (Systemic): Salicylates may enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Risk C: Monitor therapy

Dabigatran Etexilate: Aspirin may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling states that low dose aspirin could be considered, but the use of antiplatelets are not recommended for stroke prevention in patients with atrial fibrillation. Risk D: Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desirudin: Dipyridamole may enhance the adverse/toxic effect of Desirudin. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy

Dexibuprofen: Aspirin may enhance the adverse/toxic effect of Dexibuprofen. Dexibuprofen may diminish the cardioprotective effect of Aspirin. Risk X: Avoid combination

Dexketoprofen: Salicylates may enhance the adverse/toxic effect of Dexketoprofen. Dexketoprofen may diminish the therapeutic effect of Salicylates. Salicylates may decrease the serum concentration of Dexketoprofen. Management: The use of high-dose salicylates (3 g/day or more in adults) together with dexketoprofen is inadvisable. Consider administering dexketoprofen 30-120 min after or at least 8 hrs before cardioprotective doses of aspirin to minimize any possible interaction. Risk X: Avoid combination

Edoxaban: Aspirin may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Aspirin may increase the serum concentration of Edoxaban. Management: Carefully consider the anticipated risks and benefits of this combination. If combined, increased monitoring for bleeding is recommended. Risk D: Consider therapy modification

Enoxaparin: Dipyridamole may enhance the adverse/toxic effect of Enoxaparin. Specifically, the risk of bleeding may be increased. Management: If possible, discontinue dipyridamole prior to initiating enoxaparin. If coadministration is unavoidable, monitor closely for clinical and laboratory evidence of bleeding. Risk D: Consider therapy modification

Ginkgo Biloba: May enhance the anticoagulant effect of Salicylates. Management: Consider alternatives to this combination of agents. Monitor for signs and symptoms of bleeding (especially intracranial bleeding) if salicylates are used in combination with ginkgo biloba. Risk D: Consider therapy modification

Heparin: Dipyridamole may enhance the adverse/toxic effect of Heparin. Specifically, the risk of bleeding may be increased. Management: Use caution and reduce the dose of heparin or dipyridamole if these agents are combined. Risk D: Consider therapy modification

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Risk C: Monitor therapy

Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Risk X: Avoid combination

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Aspirin. An increased risk of bleeding may be associated with use of this combination. Ketorolac (Nasal) may diminish the cardioprotective effect of Aspirin. Management: Concurrent use of nasal ketorolac with analgesic doses of aspirin is generally not recommended. If using low-dose, cardioprotective aspirin with nasal ketorolac, monitor the patient closely for evidence of adverse GI effects. Risk D: Consider therapy modification

Ketorolac (Systemic): May enhance the adverse/toxic effect of Aspirin. An increased risk of bleeding may be associated with use of this combination. Ketorolac (Systemic) may diminish the cardioprotective effect of Aspirin. Risk X: Avoid combination

Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Loop Diuretics: Salicylates may diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy

Macimorelin: Aspirin may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Management: Consider avoiding coadministration of methotrexate and salicylates. If coadministration cannot be avoided, monitor for increased toxic effects of methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Nicorandil: Aspirin may enhance the adverse/toxic effect of Nicorandil. Specifically, the risk of gastrointestinal ulceration and hemorrhage may be increased. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Aspirin may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Management: Concurrent use of aspirin at doses beyond cardioprotective levels is not recommended. While concurrent use of low-dose aspirin with a COX-2 inhibitor is permissable, patients should be monitored closely for signs/symptoms of GI ulceration/bleeding. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Salicylates. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of salicylates and topical NSAIDs is not recommended. If salicylates and topical NSAIDs are coadministered, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities. Risk D: Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Aspirin may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of aspirin with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Phenindione: Dipyridamole may enhance the adverse/toxic effect of Phenindione. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of dipyridamole and phenindione if possible. If coadministration is required, monitor closely for clinical and laboratory evidence of bleeding. Risk D: Consider therapy modification

Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Potassium Phosphate: May increase the serum concentration of Salicylates. Risk C: Monitor therapy

PRALAtrexate: Salicylates may increase the serum concentration of PRALAtrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern. Management: Consider avoiding concomitant use of salicylates and pralatrexate. If coadministered, monitor for increased pralatrexate adverse effects. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Risk D: Consider therapy modification

Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Risk X: Avoid combination

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Regadenoson: Dipyridamole may enhance the adverse/toxic effect of Regadenoson. Specifically, adenosine mediated effects may be enhanced. Management: Avoid dipyridamole for 48 hours prior to the administration of regadenoson when possible. Risk D: Consider therapy modification

Riociguat: Dipyridamole may enhance the hypotensive effect of Riociguat. Risk X: Avoid combination

Rivaroxaban: Aspirin may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk D: Consider therapy modification

Salicylates: May enhance the anticoagulant effect of other Salicylates. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Spironolactone: Aspirin may diminish the therapeutic effect of Spironolactone. Risk C: Monitor therapy

Sucroferric Oxyhydroxide: May decrease the serum concentration of Aspirin. Management: Administer aspirin at least 1 hour before administration of sucroferric oxyhydroxide. Risk D: Consider therapy modification

Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. Risk X: Avoid combination

Talniflumate: Aspirin may enhance the adverse/toxic effect of Talniflumate. Management: When possible, consider alternatives to this combination. Concurrent use is generally not recommended. Risk D: Consider therapy modification

Thiopental: Aspirin may decrease the protein binding of Thiopental. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy

Ticagrelor: Aspirin may enhance the antiplatelet effect of Ticagrelor. Aspirin may diminish the therapeutic effect of Ticagrelor. More specifically, the benefits of ticagrelor relative to clopidogrel may be diminished in adult patients receiving daily aspirin doses greater than 100-150 mg daily. Management: Avoid daily aspirin doses greater than 100 mg in adults receiving ticagrelor. Canadian recommendations are to avoid adult daily aspirin doses greater than 150 mg. Daily low-dose aspirin (U.S.: 75-100 mg; Canada: 75-150 mg) is recommended. Risk D: Consider therapy modification

Tiludronate: Aspirin may decrease the serum concentration of Tiludronate. Risk C: Monitor therapy

Tinzaparin: Dipyridamole may enhance the adverse/toxic effect of Tinzaparin. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Valproate Products: Salicylates may increase the serum concentration of Valproate Products. Risk C: Monitor therapy

Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Specifically, the risk for Reye's syndrome may increase. Risk X: Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Avoid as needed use of salicylates in patients taking vitamin K antagonists. Aspirin (80 to 325 mg/day) may be used with warfarin for prevention of cardiovascular events. If coadministering salicylates and vitamin K antagonists, monitor for bledding. Risk D: Consider therapy modification

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pregnancy Considerations

Refer to individual monographs

Breastfeeding Considerations

Aspirin and dipyridamole are present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Refer to individual monographs.

Monitoring Parameters

Signs and symptoms of GI ulcers and bleeding; signs or symptoms of stroke or transient ischemic attack in patients taking concomitant aspirin therapy for cardiac indications.

Mechanism of Action

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 cyclooxygenase and thus inhibits the generation of thromboxane A2.

Pharmacokinetics (Adult Data Unless Noted)

See individual agents.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Aggrenox;
  • (AR) Argentina: Agrenox | Asasantin;
  • (AT) Austria: Asasantin | Thrombosantin;
  • (AU) Australia: Apo dipyridamole/aspirin | Asasantin | Diasp SR;
  • (BD) Bangladesh: Aggreno;
  • (BE) Belgium: Aggrenox;
  • (BR) Brazil: Persantin s;
  • (CH) Switzerland: Asasantin;
  • (CN) China: De li shu;
  • (CO) Colombia: Aggrenox | Asasantin;
  • (CZ) Czech Republic: Aggrenox;
  • (DE) Germany: Aggrenox | Asasantin | Dipyridamol Ass;
  • (EE) Estonia: Asasantin;
  • (EG) Egypt: Persantin plus;
  • (ES) Spain: Asasantin;
  • (FI) Finland: Asasantin;
  • (FR) France: Asasantine;
  • (GB) United Kingdom: Asasantin;
  • (GR) Greece: Aggrenox;
  • (HK) Hong Kong: Aggrenox | Persantin plus;
  • (HR) Croatia: Aggrenox;
  • (HU) Hungary: Asasantin;
  • (ID) Indonesia: Aggrenox;
  • (IE) Ireland: Asasantin;
  • (IT) Italy: Aggrenox;
  • (KR) Korea, Republic of: Asasantin | Dipyrin er;
  • (KW) Kuwait: Aggrenox;
  • (LT) Lithuania: Aggrenox;
  • (LU) Luxembourg: Aggrenox;
  • (MX) Mexico: Aggrenox | Asasantin | Dipiridamol + Acido Acetilsalicilico Biomep;
  • (NL) Netherlands: Asasantin;
  • (NO) Norway: Asasantin;
  • (PH) Philippines: Aggrenox;
  • (PR) Puerto Rico: Aggrenox | Aspirin and dipyridamole | Aspirin and extended release dipyridamole;
  • (PT) Portugal: Aggrenox;
  • (QA) Qatar: Aggrenox;
  • (RO) Romania: Aggrenox;
  • (SE) Sweden: Asasantin;
  • (SI) Slovenia: Asasantin;
  • (TH) Thailand: Aggrenox | Persantin plus;
  • (TW) Taiwan: Aggrenox;
  • (UY) Uruguay: Asasantin;
  • (ZA) South Africa: Asasantin
  1. Aggrenox (aspirin/dipyridamole ER) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; May 2021.
  2. Aggrenox (aspirin/dipyridamole ER) [product monograph]. Burlington, Ontario: Boehringer Ingelheim (Canada) Ltd; August 2015.
  3. Armstrong MJ, Gronseth G, Anderson DC, et al. Summary of evidence-based guideline: Periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2013;80(22):2065-2069. [PubMed 23713086]
  4. Bell AD, Roussin A, Cartier R, et al. The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines. Can J Cardiol. 2011;27(suppl A):1-59. [PubMed 21640290]
  5. Capone ML, Sciulli MG, Tacconelli S, et al. Pharmacodynamic Interaction of Naproxen With Low-Dose Aspirin in Healthy Subjects. J Am Coll Cardiol. 2005;45(8):1295-1301. [PubMed 15837265]
  6. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin. N Engl J Med. 2001;345(25):1809-1817. [PubMed 11752357]
  7. Cryer B, Verlin RG, Cooper SA, et al. Double-Blind, Randomized, Parallel, Placebo-Controlled Study of Ibuprofen Effects on Thromboxane B2 Concentrations in Aspirin-Treated Healthy Adult Volunteers. Clin Ther. 2005;27(2):185-191. [PubMed 15811481]
  8. Dixon BS, Beck GJ, Vazquez MA, et al. Effect of dipyridamole plus aspirin on hemodialysis graft patency. N Engl J Med. 2009;360(21):2191-2201. [PubMed 19458364]
  9. Grines CL, Bonow RO, Casey DE, et al. AHA/ACC/SCAI/ACS/ADA Science Advisory, Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents. A Science Advisory From the American Heart Association, American College of Cardiology, Society of Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association With Representation from the American College of Physicians. Circulation. 2007;115(6):813-818. http://circ.ahajournals.org/cgi/content/full/115/6/813 [PubMed 17224480]
  10. Guyatt GH, Akl EA, Crowther M, et al. Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(suppl):7-47. [PubMed 22315257]
  11. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association/American Stroke Association. Stroke. 2021;52(7):e364-e467. doi:10.1161/STR.0000000000000375 [PubMed 34024117]
  12. Medeiros FB, de Andrade AC, Angelis GA, et al. Bleeding Evaluation During Single Tooth Extraction in Patients With Coronary Artery Disease and Acetylsalicylic Acid Therapy Suspension: A Prospective, Double-Blinded, and Randomized Study. J Oral Maxillofac Surg. 2011;69(12):2949-2955. [PubMed 21802823]
  13. Meyers RS, Thackray J, Matson KL, et al. Key Potentially Inappropriate Drugs in Pediatrics: The KIDs List. J Pediatr Pharmacol Ther. 2020;25(3):175-191. [PubMed 32265601]
  14. Oliveira-Filho J, Mullen MT. Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 10, 2022.
  15. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418. doi:10.1161/STR.0000000000000211 [PubMed 31662037]
  16. Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: A Guideline From the American Heart Association and American College of Cardiology Foundation. Circulation. 2011;124(22):2458-2473. [PubMed 22052934]
Topic 8664 Version 322.0

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