AGGRENOX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AGGRENOX (AGGRENOX).
Aggrenox is a combination of dipyridamole and aspirin. Dipyridamole inhibits the uptake of adenosine into platelets, endothelial cells, and erythrocytes, leading to increased extracellular adenosine which stimulates platelet adenylate cyclase, increasing cAMP levels and inhibiting platelet aggregation. Aspirin irreversibly acetylates cyclooxygenase-1 (COX-1), inhibiting thromboxane A2 synthesis, thereby reducing platelet aggregation.
| Metabolism | Dipyridamole is primarily metabolized by the liver via glucuronidation, forming glucuronide conjugates. Aspirin is hydrolyzed to salicylic acid by esterases in the gastrointestinal tract, liver, and blood; salicylic acid is further metabolized by conjugation with glycine (to salicyluric acid) and glucuronic acid, and by oxidation to gentisic acid. |
| Excretion | Aspirin: renal elimination of salicylate and metabolites (primarily salicyluric acid, salicyl phenolic glucuronide, salicyl acyl glucuronide, and gentisic acid) accounts for >90% of a dose. Dipyridamole: primarily biliary excretion as glucuronide conjugates (enteric recycling); renal excretion accounts for <5% of unchanged drug. |
| Half-life | Aspirin: 15-20 minutes for parent drug; salicylate terminal half-life 3-6 hours (dose-dependent). Dipyridamole: terminal half-life approximately 10-12 hours. Clinical context: Typical twice-daily dosing maintains therapeutic antiplatelet effect. |
| Protein binding | Aspirin: 80-90% bound primarily to albumin. Dipyridamole: 99% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Aspirin: 0.15-0.3 L/kg (low Vd, mainly confined to plasma). Dipyridamole: 3-5 L/kg (extensive tissue distribution). |
| Bioavailability | Aspirin: 40-50% (oral) due to presystemic hydrolysis in GI mucosa and liver. Dipyridamole: 30-66% (oral); absorption is variable and enhanced by food (capsule formulation of Aggrenox yields ~70% bioavailability of the dipyridamole component). |
| Onset of Action | Aspirin: irreversible COX-1 acetylation within 1 hour after oral administration. Dipyridamole: peak plasma levels at approximately 2-3 hours; inhibition of adenosine uptake is rapid. |
| Duration of Action | Aspirin: antiplatelet effect lasts for the lifetime of the platelet (7-10 days). Dipyridamole: antiplatelet effect persists for 24 hours with twice-daily dosing. |
One capsule (dipyridamole 200 mg plus aspirin 25 mg) orally twice daily.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, avoid use due to aspirin component. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use with caution; no specific dose adjustment established. |
| Pediatric use | Not recommended; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; use with caution due to increased risk of bleeding and renal impairment. Monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AGGRENOX (AGGRENOX).
| Breastfeeding | Aspirin: excreted into breast milk; M/P ratio ~0.03-0.08; low dose <100 mg/day likely safe. Dipyridamole: excreted into breast milk; M/P ratio ~0.7; limited human data; use with caution. Monitor infant for bleeding or bruising. |
| Teratogenic Risk | AGGRENOX contains aspirin and dipyridamole. Aspirin: First trimester: increased risk of gastroschisis and cardiac defects; avoid high doses. Second trimester: generally safe at low doses. Third trimester: risk of premature closure of ductus arteriosus, oligohydramnios, and bleeding complications. Dipyridamole: Animal studies show no teratogenicity; limited human data. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to dipyridamole, aspirin, or any component of the formulation; history of aspirin-sensitive asthma; active peptic ulcer disease; bleeding disorders such as hemophilia or von Willebrand disease; severe hepatic impairment; children with viral infections (Reye's syndrome risk); concomitant use with oral anticoagulants may increase bleeding risk.
| Precautions | Risk of bleeding, including gastrointestinal bleeding and intracranial hemorrhage; avoid use in patients with active peptic ulcer disease; caution in patients with hypotension or hemodynamic instability; use with caution in patients with coagulation disorders or on anticoagulants; may cause hepatotoxicity with high doses; Reye's syndrome risk in children with viral infections; avoid abrupt discontinuation of dipyridamole in patients with coronary artery disease due to risk of coronary vasoconstriction. |
| Food/Dietary | Avoid alcohol because it can increase risk of gastrointestinal bleeding. No specific food restrictions; however, maintain consistent intake of grapefruit juice as it may affect dipyridamole metabolism (moderate effect, but no dose adjustment typically needed). |
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| Fetal Monitoring | Monitor maternal bleeding time, platelet count, and fetal growth ultrasound. Assess fetal well-being in third trimester; avoid use near term due to risk of premature ductus closure. |
| Fertility Effects | Aspirin may impair ovulation at high doses due to prostaglandin inhibition. Dipyridamole: no known effect on fertility. Reversible upon discontinuation. |
| Clinical Pearls | Aggrenox is a fixed-dose combination of extended-release dipyridamole and low-dose aspirin (25 mg). It is indicated for secondary stroke prevention in patients who have had a transient ischemic attack (TIA) or ischemic stroke. The dose is one capsule twice daily. Avoid use in patients with severe hepatic impairment, severe renal impairment, or hypersensitivity to NSAIDs. May cause headache upon initiation; consider dose titration or concomitant analgesics. Monitor for bleeding risk, especially with concurrent anticoagulants or antiplatelet agents. Contraindicated in patients with history of asthma, urticaria, or allergic reactions to aspirin or NSAIDs. |
| Patient Advice | Take one capsule twice daily, morning and evening, with or without food. · Do not crush or chew the capsules; swallow them whole. · Common side effects include headache, nausea, and dyspepsia. Headache may improve with continued use. · Seek medical attention if you experience signs of bleeding (unusual bruising, black or bloody stools, coughing up blood) or allergic reaction (rash, difficulty breathing). · Inform all healthcare providers (including dentists) that you are taking Aggrenox before any surgical or dental procedure. · Avoid taking additional aspirin or NSAIDs (e.g., ibuprofen, naproxen) unless specifically directed by your doctor, as this increases bleeding risk. · If you miss a dose, skip it and take the next dose at the scheduled time. Do not double the dose. |