Aggreno

• Secondary prevention of stroke and transient ischemic attack (TIA):
  For reducing the risk of recurrent ischemic stroke or TIA in patients who have had a previous episode.
• Prevention of thromboembolism:
  In patients at increased risk of clot formation, especially those with vascular disease.
• Off-label uses:
  Occasionally used for preventing vascular graft occlusion or other thrombotic events under specialist supervision.

• Adults:
• Standard fixed-dose combination: 25 mg dipyridamole sustained release + 200 mg aspirin, orally, twice daily.
• Some formulations contain 200 mg aspirin + 200 mg dipyridamole SR twice daily.
• Duration: Long-term therapy as prescribed by physician, often lifelong for stroke prevention.
• Pediatrics:
• Safety and efficacy not established; generally not recommended.
• Elderly:
• Use with caution due to increased bleeding risk; no specific dose adjustment but monitor closely.
• Renal/Hepatic Impairment:
• No dose adjustment generally required in mild to moderate impairment; caution advised in severe cases.
• Administration:
• Administer orally, preferably with food to reduce gastrointestinal discomfort.
• Swallow tablets whole; do not crush or chew sustained-release forms.

Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), reducing thromboxane A2 synthesis, which inhibits platelet aggregation and thrombus formation. Dipyridamole inhibits phosphodiesterase enzymes leading to increased intracellular cyclic AMP and cyclic GMP in platelets and vascular smooth muscle, which inhibits platelet activation and promotes vasodilation. Together, these complementary actions synergistically reduce platelet aggregation and prevent thromboembolic events.

• Absorption:
  Aspirin is rapidly absorbed and hydrolyzed to salicylic acid. Dipyridamole has variable absorption with peak plasma concentrations approximately 1.5 to 2 hours after oral administration.
• Distribution:
  Dipyridamole is highly protein-bound (>99%). Aspirin’s active metabolite is moderately protein-bound.
• Metabolism:
  Aspirin is hydrolyzed primarily in the liver to salicylic acid. Dipyridamole undergoes extensive hepatic metabolism, mainly via conjugation.
• Half-life:
  Aspirin: ~15–20 minutes (parent drug), salicylic acid half-life is dose-dependent (2–20 hours).
  Dipyridamole: approximately 10–12 hours.
• Excretion:
  Aspirin metabolites are primarily excreted via the kidneys; dipyridamole is eliminated via biliary and renal routes.

• Pregnancy:
  Category D in the third trimester due to risk of fetal harm, including premature closure of the ductus arteriosus; Category C earlier. Use only if benefits outweigh risks.
• Lactation:
  Aspirin and dipyridamole are excreted in breast milk in small amounts; breastfeeding is generally not recommended during therapy due to potential bleeding risk in the infant.

• Combination Antiplatelet Agent
• Aspirin: NSAID and antiplatelet
• Dipyridamole: Phosphodiesterase inhibitor and vasodilator

• Hypersensitivity to aspirin, dipyridamole, or any excipients.
• Active or history of significant gastrointestinal bleeding or peptic ulcer disease.
• Severe hepatic or renal impairment.
• Bleeding disorders or active bleeding.
• Children and adolescents with viral infections (risk of Reye’s syndrome).
• Third trimester pregnancy.

• Increased risk of bleeding, including gastrointestinal bleeding and hemorrhagic stroke; monitor closely.
• Caution in patients with history of asthma or aspirin-induced hypersensitivity.
• Hypotension may occur due to dipyridamole’s vasodilatory effects.
• Use with caution in patients with unstable angina or recent myocardial infarction.
• Monitor for signs of allergic reactions or angioedema.

• Common:
• Headache (due to dipyridamole-induced vasodilation)
• Gastrointestinal upset: nausea, dyspepsia, abdominal pain
• Dizziness, flushing
• Bleeding complications (e.g., bruising, epistaxis)
• Serious/Rare:
• Severe bleeding (gastrointestinal, intracranial)
• Hypersensitivity reactions including anaphylaxis
• Angioedema
• Thrombocytopenia or hemolytic anemia (rare)
• Side effects can appear early in treatment and may be dose-dependent.

• Increased bleeding risk with other anticoagulants, antiplatelets, NSAIDs, SSRIs, and thrombolytics.
• Dipyridamole may potentiate the hypotensive effects of antihypertensives.
• Avoid co-administration with adenosine or dipyridamole-containing agents due to additive vasodilatory effects.
• Smoking and other CYP450 inducers may affect dipyridamole metabolism.
• Aspirin is a CYP450-independent substrate; dipyridamole has minimal CYP450 involvement.

• Clinical guidelines recommend aspirin + dipyridamole combination as a first-line antiplatelet therapy for secondary stroke prevention.
• Some guidelines suggest equivalence or preference over clopidogrel in specific patient populations.
• Recent safety warnings emphasize bleeding risk monitoring and avoidance in patients at high bleeding risk.

• Store at 20°C to 25°C (68°F to 77°F); excursions allowed between 15°C and 30°C.
• Protect from moisture and light; keep tablets in original packaging until use.
• Do not freeze.
• Keep out of reach of children.