Aspirin and Extended-Release Dipyridamole

Aspirin and extended-release dipyridamole is a combination antiplatelet medication approved for one main purpose across both its capsule forms:

• Reducing the risk of stroke in people who have already experienced a transient ischemia of the brain (TIA, or "mini-stroke") or a completed ischemic stroke caused by a blood clot (thrombosis).

This medication works through two separate but complementary pathways — and that's exactly why the combination is more effective than either ingredient alone. Dipyridamole works by blocking the uptake of adenosine into platelets and by inhibiting an enzyme called phosphodiesterase (PDE); together, these actions raise chemical signals inside platelets that tell them to stay inactive and not clump together. Aspirin permanently disables a different enzyme — cyclooxygenase — inside platelets, stopping them from making thromboxane A2, a chemical that normally triggers platelet clumping and blood vessel narrowing. By targeting two different steps in the clotting process, the combination provides additive protection against the kind of clots that can block blood flow to the brain.

Both the capsule and the extended-release capsule forms are taken orally twice a day — one in the morning and one in the evening. Capsules must be swallowed whole (do not chew) and can be taken with or without food. If headaches are intolerable when starting treatment, your prescriber may temporarily adjust the schedule to one capsule at bedtime; the goal is to return to the standard twice-daily routine within about one week as headaches typically ease with continued use.

• Do not substitute this combination product with separate aspirin tablets and dipyridamole tablets — they are not interchangeable.
• Always follow your prescriber's specific instructions for your situation.

The most commonly reported side effects — occurring in more than 1 in 10 patients — include:

• Headache — the most frequent complaint, especially early in treatment
• Upset stomach or heartburn (dyspepsia)
• Abdominal pain
• Nausea
• Diarrhea
• Vomiting
• Dizziness
• Unusual bleeding (e.g., nosebleeds, easy bruising)

Seek prompt medical attention for signs of serious bleeding — such as black or tarry stools, vomiting blood, or bleeding that won't stop — or for chest pain, sudden severe headache, fainting, or signs of an allergic reaction like facial swelling or difficulty breathing.

• Increased bleeding risk: This is the most important safety concern. The risk is higher if you also use blood thinners, other antiplatelet drugs, NSAIDs, or drink heavily. Watch for stomach or intestinal bleeding (black stools, stomach pain) and signs of bleeding in the brain (sudden severe headache, weakness, confusion).
• Pregnancy: Avoid use in the third trimester — aspirin can cause serious harm to the unborn baby, including low birth weight, bleeding complications, and in rare cases, stillbirth or neonatal death. Talk to your doctor before using this medication if you are pregnant or planning to become pregnant.
• Children and teenagers: Do not use in children or teens with a viral illness — the aspirin component raises the risk of Reye syndrome, a rare but life-threatening condition affecting the brain and liver.
• Coronary artery disease: Dipyridamole widens blood vessels and can trigger or worsen chest pain in people with coronary artery disease. Also, the aspirin dose in this product may not be sufficient to protect against heart attack or angina on its own.
• Low blood pressure: Dipyridamole can lower blood pressure; use with care if you already have hypotension.
• Severe kidney or liver disease: Avoid this medication in patients with severe kidney failure or significant liver disease.

This medication interacts with a number of commonly used drugs and substances — always give your prescriber and pharmacist a full list of everything you take:

• Blood thinners (warfarin, heparin): Aspirin adds to their effect, significantly raising bleeding risk.
• Other antiplatelet drugs and anagrelide: Combined use increases bleeding risk further.
• NSAIDs (ibuprofen, naproxen, etc.): Concurrent use may increase bleeding and can reduce kidney function.
• Adenosine / regadenoson: Dipyridamole raises their blood and cardiovascular effects; dosing adjustment may be needed, especially around stress testing.
• ACE inhibitors: Aspirin may blunt the blood pressure-lowering effect of these heart medications.
• Beta blockers and diuretics: Aspirin may reduce the effectiveness of both by affecting kidney prostaglandins.
• Methotrexate: Aspirin can increase methotrexate levels, raising the risk of serious bone marrow toxicity — especially in older adults or those with kidney problems.
• Oral diabetes medications: Aspirin may enhance their glucose-lowering effect, potentially causing low blood sugar.
• Phenytoin / valproic acid (seizure medications): Aspirin can alter blood levels of these drugs.
• Cholinesterase inhibitors (used in myasthenia gravis or dementia): Dipyridamole may counteract their effect.
• Alcohol (3+ drinks daily): Increases bleeding risk when combined with aspirin.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Tell your prescriber about any known allergy to aspirin, NSAIDs, or any ingredient in this product — allergic reactions can be severe, including hives, swelling, or breathing trouble.
• Do not take this medication if you have asthma, nasal polyps, and chronic nasal inflammation together (a condition called aspirin-exacerbated respiratory disease).
• Do not give to children or teenagers with a viral illness (such as flu or chickenpox) — risk of Reye syndrome.
• Avoid during the third trimester of pregnancy; discuss use during earlier trimesters with your doctor, as fetal harm is possible.
• If breastfeeding, discuss with your doctor — both dipyridamole and aspirin's breakdown product (salicylic acid) pass into breast milk.
• Avoid if you have severe kidney failure (very low kidney filtration rate); use with caution and discuss with your prescriber if you have any kidney disease.
• Use with caution if you have liver disease — dipyridamole has been linked to elevated liver enzymes and, in rare cases, liver failure.
• If you have coronary artery disease or low blood pressure, let your prescriber know — dipyridamole's vessel-widening effect can worsen these conditions.
• Older adults may have higher dipyridamole levels in their blood; your prescriber should be aware of your age and any other health conditions.

An overdose of this combination is likely to show signs of dipyridamole toxicity first — including flushing, sweating, restlessness, weakness, dizziness, a drop in blood pressure, and a fast heartbeat. Too much aspirin can cause ringing in the ears (tinnitus), fever, and in severe cases, dangerous changes in body chemistry.

If you suspect an overdose, call 911 or contact Poison Control immediately (1-800-222-1222 in the US). Do not wait for symptoms to worsen — prompt medical care is essential.

Both aspirin and dipyridamole work by reducing the ability of platelets (tiny blood cells) to clump together and form clots. Dipyridamole does this by raising the level of chemical messengers inside platelets that keep them inactive, blocking their response to several clot-triggering signals. Aspirin permanently disables a key clotting enzyme in platelets, preventing production of a clot-promoting chemical called thromboxane A2. Together, their antiplatelet effects add up, providing greater clot prevention than either drug alone.

After an oral dose, dipyridamole from this combination reaches peak blood levels in about 2 hours on average, and it is almost completely bound to proteins in the bloodstream. It is broken down mainly in the liver and eliminated primarily through bile and stool. Aspirin is absorbed faster — typically within 30–60 minutes — and is converted in the liver and gut to salicylic acid; it and its byproducts are eliminated through the urine. Older adults tend to have higher dipyridamole levels in their blood compared to younger patients. Taking the capsules with a high-fat meal slightly reduces dipyridamole absorption, but this is not considered clinically meaningful.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) . Protect from excessive moisture.