Aggreno25 mg+200 mg

Aggreno is a fixed-dose antiplatelet combination (aspirin plus extended-release dipyridamole) used to reduce the risk of recurrent ischemic events in patients with a history of cerebrovascular disease.

Established/guideline-supported use

• Secondary prevention of ischemic stroke or transient ischemic attack (TIA): Aggreno is indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain (TIA) or a completed ischemic stroke due to thrombosis, based on the ESPS-2 clinical trial demonstrating superiority of the combination over either component alone or placebo.

Not established / not indicated

• Aggreno has not been shown to be effective for the treatment of acute stroke, and is not indicated for primary prevention of stroke or for prevention of cardiac events such as myocardial infarction (single-agent aspirin is preferred for those uses).
• It is not a substitute for anticoagulation in conditions such as atrial fibrillation or mechanical heart valves, where anticoagulants are the guideline-directed therapy.

Aggreno should only be used for the indication and dosing regimen for which the fixed extended-release combination has established evidence; see Precautions and Warnings.

Each capsule of Aspirin + Dipyridamole contains two active ingredients combined in a single fixed-dose, extended-release oral dosage form:

• Aspirin 25 mg (immediate-release) — an antiplatelet/salicylate.
• Dipyridamole 200 mg (extended-release) — a platelet-aggregation inhibitor and vasodilator.

The two components act through complementary mechanisms to inhibit platelet aggregation; Aspirin + Dipyridamole is typically taken as one capsule twice daily.

Aggreno is an oral, fixed-dose combination antiplatelet medicine that pairs low-dose aspirin with extended-release dipyridamole in a single capsule. It is formulated specifically for twice-daily secondary stroke prevention and is not interchangeable with separately dosed aspirin and dipyridamole tablets, because the extended-release dipyridamole component and the specific ratio of the two drugs are what has been studied in clinical trials.

Aggreno works by inhibiting platelet aggregation through two different pathways, which together reduce the likelihood of blood clots forming in the arteries that supply the brain.

Antiplatelet agent (combination) — Aggreno belongs to the therapeutic class of platelet-aggregation inhibitors used in secondary stroke prevention.

Mechanism of action

Aspirin + Dipyridamole combines two antiplatelet agents with complementary and synergistic mechanisms:

• Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1) in platelets, blocking the synthesis of thromboxane A2, a potent inducer of platelet aggregation and vasoconstriction. This effect lasts for the lifetime of the platelet (about 7–10 days).
• Dipyridamole inhibits phosphodiesterase and blocks cellular uptake of adenosine, leading to increased intracellular cyclic AMP and cyclic GMP in platelets, which reduces platelet aggregation. It also has a mild vasodilatory effect.

Pharmacokinetics

The dipyridamole component in Aspirin + Dipyridamole is formulated as an extended-release matrix to allow twice-daily dosing and to reduce the incidence of headache associated with peak plasma concentrations. Both aspirin and dipyridamole are highly protein-bound and hepatically metabolized; aspirin is hydrolyzed to salicylic acid and further conjugated, while dipyridamole undergoes glucuronidation and is primarily eliminated in bile/feces.

Oral use only. Swallow the Aggreno capsule whole with water, twice daily about 12 hours apart, with or without food. Do not crush, chew, or open the capsule.

The following interactions with Aggreno are clinically significant and well-documented:

• Anticoagulants (e.g., warfarin, heparin, direct oral anticoagulants): Concurrent use with Aggreno substantially increases the risk of bleeding; combined use requires close monitoring and is generally avoided unless specifically directed by a physician.
• Other NSAIDs and antiplatelet agents (e.g., ibuprofen, clopidogrel): Additive antiplatelet/GI-irritant effects with Aggreno increase the risk of gastrointestinal bleeding and ulceration.
• Selective serotonin reuptake inhibitors (SSRIs): May increase bleeding risk when combined with Aggreno due to additive effects on platelet function.
• Acetylcholinesterase inhibitors (e.g., donepezil, pyridostigmine): Dipyridamole in Aggreno may antagonize the anticholinesterase effect and worsen conditions such as myasthenia gravis.
• Adenosine: Dipyridamole in Aggreno inhibits adenosine metabolism/uptake and potentiates its effects; a lower adenosine dose is generally required.
• Antihypertensive agents: The mild vasodilatory effect of dipyridamole in Aggreno may add to the blood-pressure-lowering effect of antihypertensives.
• Methotrexate: Aspirin in Aggreno can reduce renal clearance of methotrexate and increase its toxicity, particularly at higher methotrexate doses.

Side effects of Aggreno are attributable to either the aspirin or the dipyridamole component:

Very common

• Headache — the most frequently reported side effect, especially during the first weeks of Aggreno therapy; often diminishes with continued use.

Common

• Dyspepsia, abdominal pain, nausea, diarrhea
• Dizziness
• Bruising or minor bleeding (e.g., nosebleeds, gum bleeding)

Less common but serious

• Gastrointestinal bleeding or ulceration
• Hypersensitivity reactions (rash, bronchospasm)
• Hypotension, flushing, or worsening of angina (dipyridamole component; see Precautions and Warnings)
• Easy or unusual bruising/bleeding suggesting a bleeding tendency

Patients should seek prompt medical attention for signs of serious bleeding (black/bloody stools, vomiting blood, unusual bruising) or chest pain while taking Aggreno.

Pregnancy: Aggreno should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus. The aspirin component, particularly in the third trimester, has been associated with risks to the fetus and complications during delivery; dipyridamole has not been well studied in human pregnancy. A physician should be consulted before using Aggreno at any stage of pregnancy.

Lactation: Aspirin and dipyridamole are both excreted into breast milk in small amounts. Because of the theoretical risk of bleeding effects and Reye's-syndrome-associated concerns with salicylates in infants, Aggreno should be used during breastfeeding only under medical supervision, after weighing benefits and risks.

The following precautions apply to Aggreno:

• Bleeding risk: Aggreno increases the risk of gastrointestinal bleeding and bruising; use with caution in patients on concurrent anticoagulants, other antiplatelet agents, or NSAIDs, and monitor for signs of bleeding (see Interactions).
• Headache: Very common, especially at the start of Aggreno therapy, from the dipyridamole component; it often improves with continued treatment. Consult a physician before stopping treatment because of headache.
• Coronary artery disease: Dipyridamole in Aggreno can theoretically worsen myocardial ischemia through a "coronary steal" phenomenon in patients with severe underlying coronary artery disease; Aggreno should be used with caution and specialist input in patients with significant coronary disease or a recent myocardial infarction.
• Hypotension: Dipyridamole in Aggreno may cause hypotension, particularly with rapid dose escalation; use caution in patients prone to low blood pressure or on antihypertensive therapy.
• Do not substitute individual components: Aggreno should not be replaced by separately dosed aspirin and immediate-release dipyridamole tablets without medical guidance, as only the specific extended-release fixed combination has demonstrated the studied efficacy and safety profile.
• General aspirin precautions: Standard precautions for aspirin apply, including risk of gastrointestinal irritation/bleeding and hypersensitivity reactions (including aspirin-sensitive asthma).

Overdose of Aggreno may present with symptoms related to either component, including severe headache, dizziness, flushing, hypotension, tinnitus, nausea, vomiting, gastrointestinal bleeding, or signs of salicylate toxicity (rapid breathing, confusion, tinnitus). In case of suspected overdose of Aggreno, seek immediate medical attention or contact a poison control center/emergency services right away. Do not attempt to treat an overdose at home; supportive care and monitoring in a medical facility are required.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly: Aggreno should be used with caution in elderly patients, who may be at higher risk of gastrointestinal bleeding and renal impairment; no specific dose adjustment is established, but close monitoring is advised.

Renal impairment: Use with caution; no formal dosing guidance is established. Monitor renal function periodically during long-term use.

Hepatic impairment: Avoid in severe hepatic impairment (see Contraindications); use with caution in mild-to-moderate impairment.

Pediatric: Not indicated in children (see Pediatric Use and Contraindications).

Pregnancy and lactation: See Pregnancy and Lactation section.

Aggreno is typically used long-term for ongoing secondary prevention of stroke/TIA, as directed by a physician. Treatment duration should be individualized and periodically reassessed; do not stop Aggreno abruptly without medical advice, as this may increase the risk of a recurrent thrombotic event.

Aspirin + Dipyridamole combines two drug classes: a salicylate/COX inhibitor (aspirin) and a phosphodiesterase inhibitor/platelet-aggregation inhibitor (dipyridamole), together classified as an antiplatelet combination agent.

Aspirin + Dipyridamole inhibits platelet aggregation through two complementary mechanisms: aspirin irreversibly blocks COX-1-mediated thromboxane A2 production in platelets, while dipyridamole inhibits phosphodiesterase and adenosine reuptake, raising platelet cyclic AMP/GMP levels and providing mild vasodilation. Together, these actions reduce the tendency of platelets to aggregate and form arterial thrombi, lowering the risk of recurrent ischemic stroke.

The safety and efficacy of Aggreno in children and adolescents have not been established. Aggreno is contraindicated in children and teenagers with, or recovering from, chickenpox or flu-like viral illness because of the risk of Reye's syndrome associated with the aspirin component (see Contraindications). Aggreno should not be used in pediatric patients outside of specialist guidance.