Aggrenox®, capsules with modified emission 30 pcs.

Agrenox is an antiplatelet. Acetylsalicylic acid inactivates the enzyme cyclooxygenase in platelets, and thus prevents the formation of thromboxane A2 – a powerful inducer of platelet aggregation and vasoconstriction.

Dipyridamole inhibits adenosine uptake in erythrocytes, platelets and endothelial cells in vivo and in vitro; inhibition reaches maximum 80% and in therapeutic concentrations (0.5-2 µg/ml) is dose dependent. As a consequence, there is a local increase in the concentration of adenosine, which acts on platelet A2-receptors, stimulating platelet adenylate cyclase, and thus increases the level of platelet u-AMP.

While acetylsalicylic acid inhibits only platelet aggregation, dipyridamole additionally inhibits platelet activation and adhesion. Therefore, an additional effect can be expected from the combination of these two drugs.

Indications

The indication for the use of the drug is secondary prevention of ischemic stroke (by the mechanism of thrombosis) and transient ischemic attacks.

Composition

1 capsule contains:

How to take, the dosage

The recommended dose is 1 capsule of Agrenox twice a day.

In general, 1 capsule is taken in the morning and 1 capsule in the evening, regardless of meals.

The capsules should be swallowed whole, without chewing, with a glass of water.

Interaction

When dipyridamole is used in combination with acetylsalicylic acid or with warfarin, precautions for these drugs should be taken into account.

Acetylsalicylic acid may increase the effect of anticoagulants (e.g., coumarin and heparin derivatives), agents that inhibit platelet aggregation (clopidogrel, ticlopidine), valproic acid and increase the risk of GI side effects when used simultaneously with NSAIDs or corticosteroids, and with systemic use of ethanol.

The combined use of dipyridamole and acetylsalicylic acid does not increase the frequency of bleeding.

Selective serotonin reuptake inhibitors may increase the risk of bleeding.

Dipyridamole increases the plasma concentration of adenosine and enhances its cardiovascular effects. Adenosine dose adjustment should be considered.

When dipyridamole and warfarin were used together, the frequency and severity of bleeding were no greater than when warfarin alone was administered.

Dipyridamole may increase the hypotensive effect of blood pressure lowering drugs and have the opposite effect of anticholinesterase, reducing the effect of cholinesterase inhibitors, and, as a consequence, cause worsening of the course of malignant myasthenia gravis.

The effects of hypoglycemic drugs and toxicity of methotrexate may be enhanced when combined with acetylsalicylic acid.

Acetylsalicylic acid may decrease the natriuretic effect of spironolactone and inhibit the effect of uricosuric drugs (e.g., probenecid, sulfinpyrazone).

The concomitant use of ibuprofen (but not other NSAIDs or paracetamol) in patients at increased risk of cardiovascular disease may limit the beneficial effect of acetylsalicylic acid on the cardiovascular system.

The drug should be used with caution in patients who are treated with drugs that increase the risk of bleeding (platelet aggregation inhibitors /clopidogrel, ticlopidine/) or selective serotonin reuptake inhibitors.

Special Instructions

Clinical experience suggests that patients receiving oral dipyridamole who also require a pharmacological stress test with intravenous dipyridamole should stop taking medications containing dipyridamole 24 hours before the test. Otherwise, the sensitivity of the test may be impaired.

In patients with malignant myasthenia gravis, adjustment of the underlying therapy may be required after changing the dose of dipyridamole.

In a small number of cases, unconjugated dipyridamole has been shown to be incorporated into gallstones to varying degrees (up to 70% of the dry weight of the stone). All patients were elderly. They had ascending cholangitis and had been receiving dipyridamole for many years. There was no evidence that dipyridamole was an initiating factor in gallstone formation. It is likely that the presence of dipyridamole in gallstones can be explained by bacterial deglucuronization of conjugated dipyridamole in bile.

The dose of acetylsalicylic acid in Agrenox (25 mg) has not been investigated for the indication of myocardial infarction prevention.

Contains 106 mg of lactose and 22.5 mg of sucrose in maximum daily dose. It should not be used in patients with hereditary intolerance to fructose and/or galactose (e.g., galactosemia).

Contraindications

With caution in patients with severe CHD, (including with unstable angina and recent myocardial infarction and with impaired left ventricular ejection or hemodynamic instability (e.g., decompensated heart failure);

as well as in patients with bronchial asthma, allergic rhinitis, nasal polyposis, chronic or recurrent gastric or duodenal ulcers, renal or hepatic dysfunction or glucose-6-phosphate dehydrogenase deficiency, with hypersensitivity to NSAIDs.

Side effects

Hypersensitivity reactions (rash, urticaria, severe bronchial spasm and angioedema) have been reported with both dipyridamole and acetylsalicylic acid.

The undesirable effects of dipyridamole in therapeutic doses are usually mild and transient. Vomiting, diarrhea and symptoms such as dizziness, nausea, headache, migraine-like headache (especially at the beginning of treatment) and myalgia have been reported during treatment with dipyridamole. These symptoms usually disappear with long-term use of the drug.

Acetylsalicylic acid may cause epigastric pain, nausea and vomiting, gastric or duodenal ulcer, and erosive gastritis, which can lead to serious gastrointestinal bleeding.

Overdose

Symptoms: due to the dosage ratio of dipyridamole and acetylsalicylic acid, in case of overdose with Agrenox, signs and symptoms of dipyridamole overdose are likely to prevail.

Experience with respect to dipyridamole overdose is limited because of the small number of observations. Symptoms such as fever, hot flashes, increased sweating, agitation, weakness, dizziness, and symptoms of angina are expected. There may be a sharp decrease in BP and tachycardia.

The symptoms of a minor acute overdose of acetylsalicylic acid are hyperventilation, tinnitus, nausea, vomiting, visual and hearing impairment, dizziness, and blurred consciousness.

Dizziness and tinnitus, especially in older patients, can be symptoms of overdose.

Treatment: symptomatic therapy, gastric lavage is carried out. Administration of xanthine derivatives (e.g., aminophylline) may neutralize the hemodynamic effects of dipyridamole overdose.

Because dipyridamole is widely distributed in tissues and is mainly eliminated by the liver, it is not excreted by hemodialysis.

Pregnancy use

The drug Agrenox is contraindicated during pregnancy (III trimester), children under 18 years of age.