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Aggrenox (Aspirin / Extended-Release Dipyridamole) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interaction Study Information Obtained From Literature

Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Adenosine

Due to the indirect effect of aspirin on the renin-angiotensin conversion pathway, the hyponatremic and hypotensive effects of ACE inhibitors may be diminished by concomitant administration of aspirin. Angiotensin Converting Enzyme (ACE) Inhibitors

Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide (and toxicity) due to competition at the renal tubule for secretion. Acetazolamide

Patients taking AGGRENOX in combination with anticoagulants, antiplatelets, or any substance impacting coagulation are at increased risk for bleeding. Aspirin can displace warfarin from protein binding sites, leading to prolongation of both the prothrombin time and the bleeding time. Aspirin can increase the anticoagulant activity of heparin, increasing bleeding risk. Anticoagulants and Antiplatelets

Salicylic acid can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels. Anticonvulsants

The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. Beta Blockers

Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors, thereby potentially aggravating myasthenia gravis. Cholinesterase Inhibitors

The effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention. Diuretics

Salicylate can inhibit renal clearance of methotrexate, leading to bone marrow toxicity, especially in the elderly or renal impaired. Methotrexate

The concurrent use of aspirin with other NSAIDs may increase bleeding or lead to decreased renal function. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Moderate doses of aspirin may increase the effectiveness of oral hypoglycemic drugs, leading to hypoglycemia. Oral Hypoglycemics

Salicylates antagonize the uricosuric action of uricosuric agents. Uricosuric Agents (probenecid and sulfinpyrazone)

OVERDOSAGE

Because of the dose ratio of dipyridamole to aspirin, overdosage of AGGRENOX is likely to be dominated by signs and symptoms of dipyridamole overdose. In case of real or suspected overdose, seek medical attention or contact a Poison Control Center immediately. Careful medical management is essential.

Based upon the known hemodynamic effects of dipyridamole, symptoms such as warm feeling, flushes, sweating, restlessness, feeling of weakness and dizziness may occur. A drop in blood pressure and tachycardia might also be observed.

Salicylate toxicity may result from acute ingestion (overdose) or chronic intoxication. Severity of aspirin intoxication is determined by measuring the blood salicylate level. The early signs of salicylic overdose (salicylism), including tinnitus (ringing in the ears), occur at plasma concentrations approaching 200 µg/mL. In severe cases, hyperthermia and hypovolemia are the major immediate threats to life. Plasma concentrations of aspirin above 300 µg/mL are clearly toxic. Severe toxic effects are associated with levels above 400 µg/mL. A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 g.

Treatment of overdose consists primarily of supporting vital functions, increasing drug elimination, and correcting acid-base disturbances. Consider gastric emptying and/or lavage as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of activated charcoal as a slurry may be beneficial if less than 3 hours have passed since ingestion. Charcoal absorption should not be employed prior to emesis and lavage. Follow acid-base status closely with serial blood gas and serum pH measurements. Maintain fluid and electrolyte balance. Administer replacement fluid intravenously and augment with correction of acidosis. Treatment may require the use of a vasopressor. Infusion of glucose may be required to control hypoglycemia.

Administration of xanthine derivatives (e.g., aminophylline) may reverse the hemodynamic effects of dipyridamole overdose. Plasma electrolytes and pH should be monitored serially to promote alkaline diuresis of salicylate if renal function is normal. In patients with renal insufficiency or in cases of life-threatening intoxication, dialysis is usually required to treat salicylic overdose, however since dipyridamole is highly protein bound, dialysis is not likely to remove dipyridamole. Exchange transfusion may be indicated in infants and young children.

CONTRAINDICATIONS

Hypersensitivity

AGGRENOX is contraindicated in patients with known hypersensitivity to any of the product components.

Allergy

Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema or bronchospasm.

Reye Syndrome

Do not use aspirin in children or teenagers with viral infections because of the risk of Reye syndrome.

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