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Aspirin and Dipyridamole


General


Pronunciation

(AS pir in & dye peer ID a mole)


Brand Names: U.S.

  • Aggrenox

Indications


Use: Labeled Indications

Stroke prevention: Reduction in the risk of stroke in patients who have had transient ischemia of the brain or complete ischemic stroke due to thrombosis.


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


Dosing and Administration


Dosing: Adult

Stroke prevention: Oral: One capsule (dipyridamole extended release 200 mg/aspirin 25 mg) twice daily

Alternative regimen for patients with intolerable headache: Oral: One capsule (dipyridamole extended release 200 mg/aspirin 25 mg) at bedtime and low-dose aspirin in the morning. Return to usual dose (1 capsule twice daily) as soon as tolerance to headache develops (usually within a week).

Carotid artery stenosis, symptomatic (including recent carotid endarterectomy) (off-label use): Oral: One capsule (dipyridamole extended release 200 mg/aspirin 25 mg) twice daily (Guyatt 2012)

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


Dosing: Renal Impairment

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

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

Severe hepatic impairment: Avoid use.


Administration

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


Storage

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


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release 12 Hour, Oral:

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

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


Drug Interactions

ACE Inhibitors: Salicylates may enhance the nephrotoxic effect of ACE Inhibitors. Salicylates may diminish the therapeutic effect of ACE Inhibitors. Monitor therapy

Acetylcholinesterase Inhibitors: Dipyridamole may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. 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: Reduction of the initial dose of adenosine may be warranted. Consider therapy modification

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

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

Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. 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. Management: Monitor patients who drink 3 or more alcoholic drinks a day for increased bleeding while taking aspirin. Counsel patients about the risk of bleeding and discourage such consumption. Give extended release aspirin 2 hours before, or 1 hour after, alcohol. Consider therapy modification

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

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

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

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

Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of Aspirin. 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. Consider therapy modification

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

Beta-Blockers: Dipyridamole may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Blood Glucose Lowering Agents: Salicylates may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

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

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. Exceptions: Brinzolamide; Dorzolamide. Consider therapy modification

Carisoprodol: Aspirin may increase serum concentrations of the active metabolite(s) of Carisoprodol. Specifically, Meprobamate concentrations may be increased. Aspirin may decrease the serum concentration of Carisoprodol. Monitor therapy

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

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. 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. 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. Consider therapy modification

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

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. Avoid combination

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

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. Consider therapy modification

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification

Floctafenine: May enhance the adverse/toxic effect of Aspirin. An increased risk of bleeding may be associated with use of this combination. Floctafenine may diminish the cardioprotective effect of Aspirin. Avoid combination

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. Consider therapy modification

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Heparin: Aspirin may enhance the anticoagulant effect of Heparin. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Consider therapy modification

Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving salicylates (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

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

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

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

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. Avoid combination

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. Avoid combination

Lesinurad: Aspirin may diminish the therapeutic effect of Lesinurad. Monitor therapy

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

Loop Diuretics: Salicylates may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Monitor therapy

Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Aspirin. Aspirin may decrease the serum concentration of Multivitamins/Fluoride (with ADE). Specifically, aspirin may decrease the absorption of ascorbic acid. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Aspirin. Aspirin may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, aspirin may decrease absorption of ascorbic acid. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Aspirin. Aspirin may decrease the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, aspirin may decrease the absorption of ascorbic acid. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

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

NSAID (COX-2 Inhibitor): Aspirin may enhance the adverse/toxic effect of NSAID (COX-2 Inhibitor). 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. Consider therapy modification

NSAID (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). 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. 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. Avoid combination

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

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

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. Monitor therapy

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

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Potassium Acid Phosphate: May increase the serum concentration of Salicylates. 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. Consider therapy modification

Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Monitor therapy

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

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

Regadenoson: Dipyridamole may enhance the adverse/toxic effect of Regadenoson. Specifically, adenosine mediated effects may be enhanced. Consider therapy modification

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Riociguat: Dipyridamole may enhance the hypotensive effect of Riociguat. 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. Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

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

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

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

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination

Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. 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. Consider therapy modification

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

Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. 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. Consider therapy modification

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

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

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

Treprostinil: May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Monitor therapy

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

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

Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Reye's Syndrome may develop. Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

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

Vitamin K Antagonists (eg, warfarin): Salicylates may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification


Monitoring Parameters

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


Lab Test Interferences


Test Interactions

See individual agents.


Adverse Reactions


>10%:

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

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

1% to 10%:

Cardiovascular: Cardiac failure (2%), syncope (1%)

Central nervous system: Fatigue (6%), pain (6%), amnesia (2%), malaise (2%), seizure (2%), confusion (1%), drowsiness (1%)

Gastrointestinal: Vomiting (8%), gastrointestinal hemorrhage (1% to 4%), melena (2%), anorexia (1%), hemorrhoids (1%)

Hematologic & oncologic: Hemorrhage (3%), anemia (2%), rectal hemorrhage (2%), purpura (1%)

Neuromuscular & skeletal: Arthralgia (6%), back pain (5%), arthritis (2%), weakness (2%), arthropathy (1%), myalgia (1%)

Respiratory: Cough (2%), epistaxis (2%), upper respiratory tract infection (1%)

<1% (Limited to important or life-threatening): Ageusia, agitation, alopecia, anaphylaxis, angina pectoris, angioedema, antepartum hemorrhage, aplastic anemia, asthma, auditory impairment, blood coagulation disorder, bronchospasm, bruise, cardiac arrhythmia, cerebral edema, cerebral hemorrhage, changes in liver function, chest pain, cholelithiasis, coma, deafness, dehydration, disseminated intravascular coagulation, dizziness, dyspnea, ecchymoses, fever, flushing, gastritis, gastrointestinal perforation, gastrointestinal ulcer, gingival hemorrhage, hematemesis, hematoma, hematuria, hemoptysis, hepatic failure, hepatitis, hyperglycemia, hyperkalemia, hypersensitivity angiitis, hypersensitivity reaction, hyperventilation, hypoglycemia, hypokalemia, hypotension, hypothermia, increased thirst, interstitial nephritis, intracranial hemorrhage, jaundice, laryngeal edema, metabolic acidosis, migraine, palpitations, pancreatitis, pancytopenia, paresthesia, postpartum hemorrhage, prolonged prothrombin time, proteinuria, pruritus, pulmonary edema, renal failure, renal insufficiency, renal papillary necrosis, respiratory alkalosis, Reyes syndrome, rhabdomyolysis, skin rash, Stevens-Johnson syndrome, subarachnoid hemorrhage, supraventricular tachycardia, tachycardia, tachypnea, thrombocythemia, thrombocytopenia, tinnitus, urticaria, uterine hemorrhage


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 NSAIDs). 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.

- 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 MI; discontinue use 24 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: Use with caution in patients with mild or moderate 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:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

- Elderly: Avoid use of oral dipyridamole in this age group due to risk of orthostatic hypotension and availability of more efficacious alternative agents (Beers Criteria).

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

- Surgical patients: ASA should be avoided (if possible) in surgical patients for 1 to 2 weeks prior to surgery, to reduce the risk of excessive bleeding.

Dosage form specific issues:

- Interchangeability: Aspirin/dipyridamole 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.


Pregnancy Risk Factor

D


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies with this combination.

Low birth weight, increased risk of intracranial hemorrhage in premature infants, still birth, and neonatal death have been reported following maternal use of aspirin in the later stages of pregnancy. Use of aspirin close to delivery may cause premature closure of the ductus arteriosus in the neonate, prolonged gestation, prolonged labor and/or excessive blood loss in the mother at delivery. Avoid aspirin/dipyridamole during the third trimester of pregnancy.


Actions


Pharmacology

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.


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience heartburn, nausea, vomiting, diarrhea, or joint pain. Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds, coughing up blood, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get bigger, or any bleeding that is very bad or that will not stop), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, arrhythmia, severe loss of strength and energy, severe headache, severe dizziness, passing out, severe abdominal pain, tinnitus, loss of hearing, urinary retention, or change in amount of urine passed (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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