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Aspirin and Extended - Release Dipyridamole Capsules, 25 mg / 200 25 mg; 200 mg Capsule, 20-count — NDC 00904-7056-99 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Aspirin and Extended - Release Dipyridamole Capsules, 25 mg / 200 25 mg; 200 mg Capsule, 20-count — NDC 0904-7056-99 (Billing 00904-7056-99)

by Major Pharmaceuticals · 20 BLISTER PACK in 1 CARTON / 1 CAPSULE in 1 BLISTER PACK

This is a package of 20 capsules of Aspirin and Extended - Release Dipyridamole Capsules, 25 mg / 200 25 mg; 200 mg Capsule from Major Pharmaceuticals, marketed since Jan 2017 and currently FDA-listed; retail pharmacies pay about $0.5586 per capsule (NADAC). It is this product's only package size.

NDC 00904-7056-99
🏷️ FDA NDC (as labeled) 0904-7056-99 billing pads the labeler segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Oct 1, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0904-7056-99
Product NDC 0904-7056
11-digit billing NDC 00904705699
NCPDP billing unit EA — each (per item)
RxCUI 259081
UNII R16CO5Y76E, 64ALC7F90C
Application # ANDA207944
SPL Set ID a6e652e1-b2e4-47ba-bed2-c5e902f8b8f1
Established class (EPC) Nonsteroidal Anti-inflammatory Drug; Platelet Aggregation Inhibitor
Mechanism of action Cyclooxygenase Inhibitors
Physiologic effect Decreased Prostaglandin Production; Decreased Platelet Aggregation
Chemical class Anti-Inflammatory Agents, Non-Steroidal
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-01-30
Route ORAL
Dosage form CAPSULE
Substance ASPIRIN; DIPYRIDAMOLE
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 040303
GCN 95347
HICL code 012474
Ingredient (HICL) Aspirin/Dipyridamole
HIC1 code M
Therapeutic class — broad (HIC1) Blood
HIC2 code M9
Therapeutic class — intermediate (HIC2) Drugs Given To Alter Blood Coagulation
HIC3 code M9P
Therapeutic class — specific (HIC3) Platelet Aggregation Inhibitors
AHFS code 20:12.18.00
AHFS class Platelet-Aggregation Inhibitors
FDB label name ASPIRIN-DIPYRIDAM ER 25-200 MG
FDB brand name Aspirin-Dipyridamole Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 040303
  • GCN: 95347
  • HICL (First Databank): 012474
  • AHFS class code: 20:12.18.00
  • RxCUI (RxNorm): 259081
Why two NDCs? The FDA registers this code as 0904-7056-99 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00904-7056-99. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Platelet Aggregation Inhibitor class.

Pharmacologic class Platelet Aggregation Inhibitor, Nonsteroidal Anti-inflammatory Drug
Drug family (ATC) Other agents for local oral treatment, Platelet aggregation inhibitors excl. heparin, Salicylic acid and derivatives
How it works Cyclooxygenase Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name ASPIRIN-DIPYRIDAM ER 25-200 MG Ingredient Aspirin/Dipyridamole
📖 What it is MedlinePlus · NLM

The combination of aspirin and extended-release dipyridamole is used to reduce the risk of stroke in patients who have had or are at risk of stroke. It is in a class of drugs called antiplatelet agents. It works by preventing excessive blood clotting.

Read the full MedlinePlus article ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $0.559 $11.17 / 20 capsule
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
NADAC price history (per ea) — tap or hover for the price & month
Jun 2022 Dec 2023 Mar 2026 Sep 2026 $0.891 $0.556
▼ Down 37% over the last 19 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
00904-7056-99 You're viewing this Main listing 20 BLISTER PACK in 1 CARTON / 1 CAPSULE in 1 BLISTER PACK 2017-01-30 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Aspirin and Extended - Release Dipyridamole Capsules, 25 mg / 200 mg 25 mg/1; 200 mgthis 00904-7056-99 Major 20 capsules $0.559 AB Availability likely —
Aspirin and Dipyridamole 25 mg/1; 200 mg 16714-0964-01 NorthStar 60 capsules $0.559 AB Availability likely —
Aspirin And Extended-Release Dipyridamole 25 mg/1; 200 mg 42571-0274-60 Micro 60 capsules $0.559 AB Availability likely —
Aspirin and Dipyridamole 25 mg/1; 200 mg 43598-0339-60 Dr. 60 capsules $0.559 AB Availability likely —
Aspirin and Extended - Release Dipyridamole Capsules, 25 mg / 200 mg 25 mg/1; 200 mg 49884-0007-02 Par 60 capsules $0.559 AB Availability likely —
Aspirin and Extended-Release Dipyridamole 25 mg/1; 200 mg 65162-0596-06 Amneal 60 capsules $0.559 AB Availability likely —
Aspirin and Extended-Release Dipyridamole 25 mg/1; 200 mg 42291-0116-60 AvKARE 60 capsules — AB FDA listed —
Aspirin And Extended-Release Dipyridamole 25 mg/1; 200 mg 63629-5045-01 Bryant 90 capsules — AB FDA listed —
Asprin And Extended-Release Dipyridamole 25 mg/1; 200 mg 68462-0405-30 Glenmark 30 capsules — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2017
On the market since
Jan 2017
📍
2026
Currently FDA-listed
9 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color Red / White
ShapeCapsule
ImprintPAR;730
Size24 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 5C5403N26O
    Acacia is a natural gum derived from acacia tree sap. It serves as a binder, thickener, and emulsifier to help hold ingredients together, improve texture, and stabilize the medicine.
  • UNII 8C3Z4148WZ
    Alginic acid is a natural polymer extracted from brown seaweed. In medicines, it acts as a thickener, binder, and disintegrant to help form tablets and control how quickly the medicine dissolves.
  • UNII 3SY5LH9PMK
    Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
  • UNII 7Z8S9VYZ4B
    Ethylcellulose is a plant-derived thickener and film-former made by chemically modifying cellulose. It's used as a binder to hold tablet ingredients together, a coating to control how quickly medicine is released, or a thickener in liquid formulations.
  • UNII WZB9127XOA
    A synthetic red dye used to color medications and make them easier to identify. It serves as a colorant in tablets, capsules, and liquid formulations.
  • UNII H77VEI93A8
    A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • UNII XM0M87F357
    A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
  • UNII 2G86QN327L
    Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
  • UNII 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • UNII 532B59J990
    Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.
  • UNII WZH3C48M4T
    Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII 46N107B71O
    Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 368GB5141J
    A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
  • UNII O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • UNII 4ELV7Z65AP
    Stearic acid is a fatty acid derived from plant or animal sources. It acts as a binder and lubricant in tablets and capsules, helping them hold together and flow smoothly during manufacturing.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • UNII W4888I119H
    Tartaric acid is a natural organic acid found in grapes and tamarinds. In medicines, it works as a buffer to control acidity, an antioxidant to prevent spoilage, and sometimes a flavoring or binding agent.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
  • UNII XHX3C3X673
    Triacetin is a clear, oily liquid made from glycerin and acetic acid. It works as a plasticizer and solvent in medicines, helping soften coatings and improve how liquids mix together in formulations.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
  • UNII TTV12P4NEE
    Xanthan gum is a thickening and stabilizing ingredient made from fermented corn or other sugars. It's added to medicines to improve texture, prevent separation of liquids and solids, and help the product stay consistent.

25 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerMajor Pharmaceuticals
Application holderPH HEALTH LTD
FDA applicationANDA207944 (ANDA)
Labeler code00904
First marketedJan 2017
Product typeHuman Prescription Drug
Portfolio630 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 76 words ▾

1 INDICATIONS AND USAGE Aspirin and Extended-Release Dipyridamole Capsule is indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis. • Aspirin and Extended-Release Dipyridamole Capsule is a combination of aspirin and dipyridamole, antiplatelet agents, indicated to reduce the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis ( 1 )

⏱️ Dosage and Administration 203 words ▾

2 DOSAGE AND ADMINISTRATION Aspirin and Extended-Release Dipyridamole Capsules are not interchangeable with the individual components of aspirin and dipyridamole tablets. The recommended dose of Aspirin and Extended-Release Dipyridamole Capsules is one capsule given orally twice daily, one in the morning and one in the evening. Swallow capsules whole without chewing.

Aspirin and Extended-Release Dipyridamole Capsules can be administered with or without food. • One capsule twice daily (morning and evening) with or without food ( 2 ) • In case of intolerable headaches during initial treatment, switch to one capsule at bedtime and low-dose aspirin in the morning; resume BID dosing within one week ( 2.1 ) • Do not chew capsule ( 2 ) • Not interchangeable with the individual components of aspirin and dipyridamole tablets ( 2 ) • Dispense in this unit-of-use container ( 16 )

2.1Alternative Regimen in Case of Intolerable Headaches In the event of intolerable headaches during initial treatment, switch to one capsule at bedtime and low-dose aspirin in the morning. Because there are no outcome data with this regimen and headaches become less of a problem as treatment continues, patients should return to the usual regimen as soon as possible, usually within one week.

💊 Dosage Forms and Strengths 55 words ▾

3 DOSAGE FORMS AND STRENGTHS 25 mg/200 mg capsules are imprinted in black with ‘PAR’ on the cap and ‘730’ on the body, containing yellow colored extended-release pellets incorporating dipyridamole and a white to off white, film coated, circular, bi-convex tablet incorporating immediate-release aspirin. • Capsule: 25 mg aspirin/200 mg extended-release dipyridamole ( 3 )

⛔ Contraindications 111 words ▾

4 CONTRAINDICATIONS • Hypersensitivity to any product ingredients ( 4.1 ) • Patients with known allergy to NSAIDs ( 4.2 ) • Patients with the syndrome of asthma, rhinitis, and nasal polyps ( 4.2 )

4.1Hypersensitivity Aspirin and extended-release dipyridamole is contraindicated in patients with known hypersensitivity to any of the product components.

4.2Allergy Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug (NSAID) products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema or bronchospasm.

4.3Reye Syndrome Do not use aspirin in children or teenagers with viral infections because of the risk of Reye syndrome.

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Aspirin and extended-release dipyridamole capsules increases the risk of bleeding ( 5.1 ) • Avoid use in patients with severe hepatic or renal insufficiency ( 5.2 , 5.3 ) • Interrupt aspirin and extended-release dipyridamole capsules 48 hours before using intravenous dipyridamole or other adenosinergic agents for stress testing ( 5.6 , 7.1 )

5.1Risk of Bleeding Aspirin and extended-release dipyridamole increases the risk of bleeding. Risk factors for bleeding include the use of other drugs that increase the risk of bleeding (e.g., anticoagulants, antiplatelet agents, heparin, anagrelide, fibrinolytic therapy, and chronic use of NSAIDs) [see Drug Interactions ( 7.1 )]. Intracranial Hemorrhage In European Stroke Prevention Study-2 (ESPS2), the annualized event rate for intracranial hemorrhage was 0.39%/year in the aspirin and extended-release dipyridamole group, 0.26%/year in the extended-release dipyridamole (ER-DP) group, 0.24%/year in the aspirin (ASA) group, and 0.29%/year in the placebo groups.

Gastrointestinal (GI) Side Effects GI side effects include stomach pain, heartburn, nausea, vomiting, and gross GI bleeding. Although minor upper GI symptoms, such as dyspepsia, are common and can occur anytime during therapy, physicians should remain alert for signs of ulceration and bleeding, even in the absence of previous GI symptoms. Inform patients about the signs and symptoms of GI side effects and what steps to take if they occur .

In ESPS2, the annualized event rate for gastrointestinal bleeding was 2.97%/year in the aspirin and extended-release dipyridamole group, 1.58%/year in the extended-release dipyridamole group, 2.06%/year in the aspirin group, and 1.40%/year in the placebo groups. Peptic Ulcer Disease Avoid using aspirin in patients with a history of active peptic ulcer disease, which can cause gastric mucosal irritation and bleeding. Alcohol Warning Because aspirin and extended-release dipyridamole contains aspirin, counsel patients who consume three or more alcoholic drinks every day about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin.

5.2Renal Failure Avoid aspirin in patients with severe renal failure (glomerular filtration rate less than 10 mL/minute) [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )].

5.3Hepatic Insufficiency Elevations of hepatic enzymes and hepatic failure have been reported in association with dipyridamole administration [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )].

5.4Coronary Artery Disease Dipyridamole has a vasodilatory effect. Chest pain may be precipitated or aggravated in patients with underlying coronary artery disease who are receiving dipyridamole. For stroke or TIA patients for whom aspirin is indicated to prevent recurrent myocardial infarction (MI) or angina pectoris, the aspirin in this product may not provide adequate treatment for the cardiac indications.

5.5Hypotension Dipyridamole produces peripheral vasodilation, which can exacerbate pre-existing hypotension.

5.6Stress Testing with Intravenous Dipyridamole and Other Adenosinergic Agents Clinical experience suggests that patients being treated with aspirin and extended-release dipyridamole capsules who also require pharmacological stress testing with intravenous dipyridamole or other adenosinergic agents (e.g., adenosine, regadenoson) should interrupt aspirin and extended-release dipyridamole capsules for 48 hours prior to stress testing [see Drug Interactions ( 7.1 )] . Intake of aspirin and extended-release dipyridamole capsules within 48 hours prior to stress testing with intravenous dipyridamole or other adenosinergic agents may increase the risk for cardiovascular side effects of these agents and may impair the sensitivity of the test.

5.7General Aspirin and extended-release dipyridamole capsules are not interchangeable with the individual components of aspirin and dipyridamole tablets.

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the labeling: • Hypersensitivity [see Contraindications ( 4.1 )] • Allergy [see Contraindications ( 4.2 )] • Risk of Bleeding [see Warnings and Precautions ( 5.1 )] • The most frequently reported adverse reactions (>10% and greater than placebo) were headache, dyspepsia, abdominal pain, nausea, and diarrhea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Par Health at 1-800-828-9393 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The efficacy and safety of aspirin and extended-release dipyridamole was established in the European Stroke Prevention Study-2 (ESPS2). ESPS2 was a double-blind, placebo-controlled study that evaluated 6602 patients over the age of 18 years who had a previous ischemic stroke or transient ischemic attack within ninety days prior to entry.

Patients were randomized to either aspirin and extended-release dipyridamole, aspirin, ER-DP, or placebo [see Clinical Studies ( 14 )] ; primary endpoints included stroke (fatal or nonfatal) and death from all causes. This 24-month, multicenter, double-blind, randomized study (ESPS2) was conducted to compare the efficacy and safety of aspirin and extended-release dipyridamole with placebo, extended-release dipyridamole alone and aspirin alone. The study was conducted in a total of 6602 male and female patients who had experienced a previous ischemic stroke or transient ischemia of the brain within three months prior to randomization.

Table 1 presents the annualized event rate for adverse events that occurred in 1%/year or more of patients treated with aspirin and extended-release dipyridamole where the incidence was also at least 1%/year greater than in those patients treated with placebo. There is no clear benefit of the dipyridamole/aspirin combination over aspirin with respect to safety. Table 1 Incidence of Adverse Events in ESPS2 a Individual Treatment Group Body System/Preferred Term Aspirin and Extended-Release Dipyridamole n (%/year) b ER-DP Alone n (%/year) b ASA Alone n (%/year) b Placebo n (%/year) b Total Number of Patients 1,650 1,654 1,649 1,649 Central and Peripheral Nervous System Disorders Headache 647 (28.25) 634 (27.91) 558 (22.10) 543 (22.29) Gastrointestinal System Disorders Dyspepsia 303 (13.23) 288 (12.68) 299 (11.84) 275 (11.29) Abdominal Pain 289 (12.62) 255 (11.22) 262 (10.38) 239 (9.81) Nausea 264 (11.53) 254 (11.18) 210 (8.32) 232 (9.53) Diarrhea 210 (9.17) 257 (11.31) 112 (4.44) 161 (6.61) Vomiting 138 (6.03) 129 (5.68) 101 (4.00) 118 (4.84) Platelet, Bleeding and Clotting Disorders Hemorrhage NOS 52 (2.27) 24 (1.06) 46 (1.82) 24 (0.99) a Reported by ≥1%/year of patients during aspirin and extended-release dipyridamole treatment where the incidence was at least 1%/year greater than in those treated with placebo. b Annual event rate per 100 pt-years = 100* number of subjects with event/subject-years.

Subject-years is defined as cumulative number of days on treatment divided by 365.25. Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dosage regimen for all treatment groups is BID.

NOS = not otherwise specified. Discontinuation due to adverse events in ESPS2 was 25% for aspirin and extended-release dipyridamole, 25% for extended-release dipyridamole, 19% for aspirin, and 21% for placebo (refer to Table 2). Table 2 Incidence of Adverse Events that Led to the Discontinuation of Treatment a Treatment Groups Aspirin and Extended-Release Dipyridamole n (%/year) b ER-DP n (%/year) b ASA n (%/year) b Placebo n (%/year) b Total Number of Patients 1,650 1,654 1,649 1,649 Patients with at least one Adverse Event that led to treatment discontinuation… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS • Co-administration with anticoagulants, antiplatelets, or NSAIDs can increase risk of bleeding ( 7.1 ) • Decreased renal function can occur with co-administration with NSAIDs ( 7.1 )

7.1Drug Interaction Study Information Obtained From Literature Adenosinergic agents (e.g., adenosine, regadenoson) Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Dipyridamole also increases the cardiovascular effects of regadenoson, an adenosine A 2A -receptor agonist.

The potential risk of cardiovascular side effects with intravenous adenosinergic agents may be increased during the testing period when dipyridamole is not held 48 hours prior to stress testing. Angiotensin Converting Enzyme (ACE) Inhibitors Because of 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. Acetazolamide 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.

Anticoagulants and Antiplatelets Patients taking aspirin and extended-release dipyridamole 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.

Anagrelide Patients taking aspirin in combination with anagrelide are at an increased risk of bleeding. Anticonvulsants 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. Beta Blockers 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.

Cholinesterase Inhibitors Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors, thereby potentially aggravating myasthenia gravis. Diuretics 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. Methotrexate Salicylate can inhibit renal clearance of methotrexate, leading to bone marrow toxicity, especially in the elderly or renal impaired.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) The concurrent use of aspirin with other NSAIDs may increase bleeding or lead to decreased renal function. Oral Hypoglycemics Moderate doses of aspirin may increase the effectiveness of oral hypoglycemic drugs, leading to hypoglycemia. Uricosuric Agents (probenecid and sulfinpyrazone) Salicylates antagonize the uricosuric action of uricosuric agents.

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Because of the dose ratio of dipyridamole to aspirin, overdosage of aspirin and extended-release dipyridamole 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 mcg/mL. In severe cases, hyperthermia and hypovolemia are the major immediate threats to life.

Plasma concentrations of aspirin above 300 mcg/mL are clearly toxic. Severe toxic effects are associated with levels above 400 mcg/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 vasodilatory 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.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The antithrombotic action of aspirin and extended-release dipyridamole is the result of the additive antiplatelet effects of dipyridamole and aspirin. Dipyridamole Dipyridamole inhibits the uptake of adenosine into platelets, endothelial cells and erythrocytes in vitro and in vivo ; the inhibition occurs in a dose-dependent manner at therapeutic concentrations (0.5 to 1.9 mcg/mL). This inhibition results in an increase in local concentrations of adenosine which acts on the platelet A 2 -receptor thereby stimulating platelet adenylate cyclase and increasing platelet cyclic-3',5'-adenosine monophosphate (cAMP) levels.

Via this mechanism, platelet aggregation is inhibited in response to various stimuli such as platelet activating factor (PAF), collagen and adenosine diphosphate (ADP). Dipyridamole inhibits phosphodiesterase (PDE) in various tissues. While the inhibition of cAMP-PDE is weak, therapeutic levels of dipyridamole inhibit cyclic-3',5'‑-guanosine monophosphate-PDE (cGMP-PDE), thereby augmenting the increase in cGMP produced by EDRF (endothelium-derived relaxing factor, now identified as nitric oxide).

Aspirin Aspirin inhibits platelet aggregation by irreversible inhibition of platelet cyclooxygenase and thus inhibits the generation of thromboxane A 2 , a powerful inducer of platelet aggregation and vasoconstriction.

12.2Pharmacodynamics The effect of either agent on the other's inhibition of platelet reactivity has not been evaluated.

12.3Pharmacokinetics There are no significant interactions between aspirin and dipyridamole. The kinetics of the components are unchanged by their co-administration as aspirin and extended-release dipyridamole. Absorption Dipyridamole: Peak plasma levels of dipyridamole are achieved 2 hours (range 1 to 6 hours) after administration of a daily dose of 400 mg aspirin and extended-release dipyridamole (given as 200 mg BID).

The peak plasma concentration at steady-state is 1.98 mcg/mL (1.01 to 3.99 mcg/mL) and the steady-state trough concentration is 0.53 mcg/mL (0.18 to 1.01 mcg/mL). Aspirin: Peak plasma levels of aspirin are achieved 0.63 hours (0.5 to 1 hour) after administration of a 50 mg aspirin daily dose from aspirin and extended-release dipyridamole (given as 25 mg BID). The peak plasma concentration at steady-state is 319 ng/mL (175 to 463 ng/mL).

Aspirin undergoes moderate hydrolysis to salicylic acid in the liver and the gastrointestinal wall, with 50% to 75% of an administered dose reaching the systemic circulation as intact aspirin. Effect of Food Dipyridamole: When aspirin and extended-release dipyridamole capsules were taken with a high fat meal, dipyridamole peak plasma levels (C max ) and total absorption (AUC) were decreased at steady-state by 20 to 30% compared to fasting. Due to the similar degree of inhibition of adenosine uptake at these plasma concentrations, this food effect is not considered clinically relevant.

Aspirin: When aspirin and extended-release dipyridamole capsules were taken with a high fat meal, there was no difference for aspirin in AUC at steady-state, and the approximately 50% decrease in C max was not considered clinically relevant based on a similar degree of cyclooxygenase inhibition comparing the fed and fasted state. Distribution Dipyridamole: Dipyridamole is highly lipophilic (log P=3.71, pH=7); however, it has been shown that the drug does not cross the blood-brain barrier to any significant extent in animals.

The steady-state volume of distribution of dipyridamole is about 92 L. Approximately 99% of dipyridamole is bound to plasma proteins, predominantly to alpha 1-acid glycoprotein and albumin. Aspirin: Aspirin is poorly bound to plasma proteins and its apparent volume of distribution is low (10 L).

Its metabolite, salicylic acid, is highly bound to plasma proteins, but its binding is concentration-dependent (nonlinear). At low concentrations (<100 mcg/mL), approximately 90% of salicylic acid… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 179 words ▾

12.1Mechanism of Action The antithrombotic action of aspirin and extended-release dipyridamole is the result of the additive antiplatelet effects of dipyridamole and aspirin. Dipyridamole Dipyridamole inhibits the uptake of adenosine into platelets, endothelial cells and erythrocytes in vitro and in vivo ; the inhibition occurs in a dose-dependent manner at therapeutic concentrations (0.5 to 1.9 mcg/mL). This inhibition results in an increase in local concentrations of adenosine which acts on the platelet A 2 -receptor thereby stimulating platelet adenylate cyclase and increasing platelet cyclic-3',5'-adenosine monophosphate (cAMP) levels.

Via this mechanism, platelet aggregation is inhibited in response to various stimuli such as platelet activating factor (PAF), collagen and adenosine diphosphate (ADP). Dipyridamole inhibits phosphodiesterase (PDE) in various tissues. While the inhibition of cAMP-PDE is weak, therapeutic levels of dipyridamole inhibit cyclic-3',5'‑-guanosine monophosphate-PDE (cGMP-PDE), thereby augmenting the increase in cGMP produced by EDRF (endothelium-derived relaxing factor, now identified as nitric oxide).

Aspirin Aspirin inhibits platelet aggregation by irreversible inhibition of platelet cyclooxygenase and thus inhibits the generation of thromboxane A 2 , a powerful inducer of platelet aggregation and vasoconstriction.

📦 How Supplied / Storage and Handling 145 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Aspirin and Extended-Release Dipyridamole Capsules are available as a hard gelatin capsule, with a red colored cap and an ivory-colored body, containing yellow colored extended-release pellets incorporating dipyridamole and a white to off white, film coated, circular, bi-convex tablet incorporating immediate-release aspirin. The capsule body is imprinted in black with ‘PAR’ on the cap and ‘730’ on the body. Aspirin and Extended-Release Dipyridamole Capsules are supplied Cartons of 20 extended-release capsules (4 extended-release capsules each blister pack x 5), NDC 0904-7056-99 WARNING: This Unit Dose package is not child resistant and is Intended for Institutional Use Only.

Keep this and all drugs out of the reach of children. Store at 25 ° C (77 ° F); excursions permitted to 15 ° to 30 ° C (59 ° to 86 ° F) [See USP Controlled Room Temperature]. Protect from excessive moisture.

📋 Description 218 words ▾

11 DESCRIPTION Aspirin and Extended-Release Dipyridamole Capsules are a combination of aspirin and dipyridamole, antiplatelet agents, intended for oral administration. Each hard gelatin capsule contains 200 mg dipyridamole in an extended-release form and 25 mg aspirin, as an immediate-release tablet. In addition, each capsule contains the following inactive ingredients: acacia, alginic acid, anhydrous lactose, colloidal silicon dioxide, ethyl cellulose, hypromellose phthalate, hypromellose, lecithin, xanthan gum, polyvinyl alcohol, povidone, pregelatinized starch, stearic acid, talc, tartaric acid, titanium dioxide and triacetin.

Each capsule shell contains gelatin, sodium lauryl sulfate, FD&C Red 40, FD&C Yellow 6, shellac, potassium hydroxide, red iron oxide, yellow iron oxide, titanium dioxide, black iron oxide and water. Dipyridamole Dipyridamole is an antiplatelet agent chemically described as 2,2',2'',2'''-[(4,8-Dipiperidinopyrimido[5,4- d ]pyrimidine-2,6-diyl)dinitrilo]-tetraethanol. It has the following structural formula: Dipyridamole is an intensely yellow crystalline powder, having a bitter taste.

It is soluble in dilute acids, methanol and chloroform, and is practically insoluble in water. Aspirin The antiplatelet agent aspirin (acetylsalicylic acid) is chemically known as benzoic acid, 2- (acetyloxy)-, and has the following structural formula: Aspirin is an odorless white crystals, commonly tabular or needle-like or white crystalline or powder. When exposed to moisture, aspirin hydrolyzes into salicylic and acetic acids, and gives off a vinegary odor.

It is highly lipid soluble and slightly soluble in water. Dipyridamole aspirin

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). • Risk of Bleeding Inform patients that as with other antiplatelet agents, there is a general risk of bleeding including intracranial and gastrointestinal bleeding. Inform patients about the signs and symptoms of bleeding, including occult bleeding. Tell patients to notify their physician if they are prescribed any drug which may increase risk of bleeding.

Counsel patients who consume three or more alcoholic drinks daily about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin. • Pregnancy Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with aspirin and extended-release dipyridamole capsules [see Use in Specific Populations ( 8.1 )] . • Headaches Some patients may experience headaches upon treatment initiation; these are usually transient. In case of intolerable headaches, tell patients to contact their physician.

Stress Test Instruct patients who are scheduled to undergo a pharmacologic stress test to tell their healthcare provider that they are taking aspirin and extended-release dipyridamole capsules. • Dosage and Administration Tell patients that aspirin and extended-release dipyridamole capsules should be swallowed whole, and not chewed or crushed. If you miss a dose, continue with your next dose on your regular schedule. Do not take a double dose. • Storage Inform patients to protect aspirin and extended-release dipyridamole capsules from moisture.

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics There are no significant interactions between aspirin and dipyridamole. The kinetics of the components are unchanged by their co-administration as aspirin and extended-release dipyridamole. Absorption Dipyridamole: Peak plasma levels of dipyridamole are achieved 2 hours (range 1 to 6 hours) after administration of a daily dose of 400 mg aspirin and extended-release dipyridamole (given as 200 mg BID).

The peak plasma concentration at steady-state is 1.98 mcg/mL (1.01 to 3.99 mcg/mL) and the steady-state trough concentration is 0.53 mcg/mL (0.18 to 1.01 mcg/mL). Aspirin: Peak plasma levels of aspirin are achieved 0.63 hours (0.5 to 1 hour) after administration of a 50 mg aspirin daily dose from aspirin and extended-release dipyridamole (given as 25 mg BID). The peak plasma concentration at steady-state is 319 ng/mL (175 to 463 ng/mL).

Aspirin undergoes moderate hydrolysis to salicylic acid in the liver and the gastrointestinal wall, with 50% to 75% of an administered dose reaching the systemic circulation as intact aspirin. Effect of Food Dipyridamole: When aspirin and extended-release dipyridamole capsules were taken with a high fat meal, dipyridamole peak plasma levels (C max ) and total absorption (AUC) were decreased at steady-state by 20 to 30% compared to fasting. Due to the similar degree of inhibition of adenosine uptake at these plasma concentrations, this food effect is not considered clinically relevant.

Aspirin: When aspirin and extended-release dipyridamole capsules were taken with a high fat meal, there was no difference for aspirin in AUC at steady-state, and the approximately 50% decrease in C max was not considered clinically relevant based on a similar degree of cyclooxygenase inhibition comparing the fed and fasted state. Distribution Dipyridamole: Dipyridamole is highly lipophilic (log P=3.71, pH=7); however, it has been shown that the drug does not cross the blood-brain barrier to any significant extent in animals.

The steady-state volume of distribution of dipyridamole is about 92 L. Approximately 99% of dipyridamole is bound to plasma proteins, predominantly to alpha 1-acid glycoprotein and albumin. Aspirin: Aspirin is poorly bound to plasma proteins and its apparent volume of distribution is low (10 L).

Its metabolite, salicylic acid, is highly bound to plasma proteins, but its binding is concentration-dependent (nonlinear). At low concentrations (<100 mcg/mL), approximately 90% of salicylic acid is bound to albumin. Salicylic acid is widely distributed to all tissues and fluids in the body, including the central nervous system, breast milk, and fetal tissues.

Early signs of salicylate overdose (salicylism), including tinnitus (ringing in the ears), occur at plasma concentrations approximating 200 mcg/mL [see Overdosage ( 10 )] . Metabolism and Elimination Dipyridamole: Dipyridamole is metabolized in the liver, primarily by conjugation with glucuronic acid, of which monoglucuronide which has low pharmacodynamic activity is the primary metabolite. In plasma, about 80% of the total amount is present as parent compound and 20% as monoglucuronide.

Most of the glucuronide metabolite (about 95%) is excreted via bile into the feces, with some evidence of enterohepatic circulation. Renal excretion of parent compound is negligible and urinary excretion of the glucuronide metabolite is low (about 5%). With intravenous (i.v.) treatment of dipyridamole, a triphasic profile is obtained: a rapid alpha phase, with a half-life of about 3.4 minutes, a beta phase, with a half-life of about 39 minutes, (which, together with the alpha phase accounts for about 70% of the total area under the curve, AUC) and a prolonged elimination phase λ z with a half-life of about 15.5 hours.

Because of the extended absorption phase of the dipyridamole component, only the terminal phase is apparent from oral treatment with aspirin and extended-release dipyridamole which was 13.6 hours. Aspirin: Aspirin is rapidly hydro… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 18 words ▾

12.2Pharmacodynamics The effect of either agent on the other's inhibition of platelet reactivity has not been evaluated.

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES ESPS2 (European Stroke Prevention Study-2) was a double-blind, placebo-controlled, 24-month study in which 6602 patients over the age of 18 years had an ischemic stroke (76%) or transient ischemic attack (TIA, 24%) within three months prior to entry. Patients were enrolled in 13 European countries between February 1989 and May 1995 and were randomized to one of four treatment groups: Aspirin and extended-release dipyridamole 25 mg/200 mg; extended-release dipyridamole (ER-DP) 200 mg alone; aspirin (ASA) 25 mg alone; or placebo.

The mean age in this population was 66.7 years with 58% of them being males. Patients received one capsule twice daily (morning and evening). Efficacy assessments included analyses of stroke (fatal or nonfatal) and death (from all causes) as confirmed by a blinded morbidity and mortality assessment group.

There were no differences with regard to efficacy based on age or gender; patients who were older had a trend towards more events. Stroke Endpoint Aspirin and extended-release dipyridamole reduced the risk of stroke by 22.1% compared to aspirin 50 mg/day alone (p = 0.008) and reduced the risk of stroke by 24.4% compared to extended-release dipyridamole 400 mg/day alone (p = 0.002) (Table 3). Aspirin and extended-release dipyridamole reduced the risk of stroke by 36.8% compared to placebo (p <0.001).

Table 3 Summary of First Stroke (Fatal or Nonfatal): ESPS2: Intent-to-Treat Population Total Number of Patients n Number of Patients With Stroke Within 2 Years n (%) Kaplan-Meier Estimate of Survival at 2 Years (95% C.I.) Gehan-Wilcoxon Test P-value Risk Reduction at 2 Years Odds Ratio (95% C.I.) Individual Treatment Group Aspirin and Extended-Release Dipyridamole 1650 157 (9.5%) 89.9% (88.4%, 91.4%) - - - ER-DP 1654 211 (12.8%) 86.7% (85.0%, 88.4%) - - - ASA 1649 206 (12.5%) 87.1% (85.4%, 88.7%) - - - Placebo 1649 250 (15.2%) 84.1% (82.2%, 85.9%) - - - Pairwise Treatment Group Comparisons Aspirin and Extended-Release Dipyridamole vs.

ER-DP _ _ _ 0.002 b 24.4% 0.72 (0.58, 0.90) Aspirin and Extended-Release Dipyridamole vs. ASA _ _ _ 0.008 b 22.1% 0.74 (0.59, 0.92) Aspirin and Extended-Release Dipyridamole vs. Placebo _ _ _ <0.001 b 36.8% 0.59 (0.48, 0.73) ER-DP vs.

Placebo _ _ _ 0.036 a 16.5% 0.82 (0.67, 1.00) ASA vs. Placebo _ _ _ 0.009 b 18.9% 0.80 (0.66, 0.97) a 0.010 <p-value < 0.050; b p-value < 0.010. Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg.

The dosage regimen for all treatment groups is BID. Figure 1 ESPS2: Cumulative Stroke Rate (Fatal or Nonfatal) Over 24 months of Follow-Up Combined Stroke or Death Endpoint In ESPS2, aspirin and extended-release dipyridamole reduced the risk of stroke or death by 24.2% compared to placebo. Aspirin and extended-release dipyridamole reduced the risk of stroke or death by 12.1% compared to aspirin alone and by 10.3% compared to extended-release dipyridamole alone.

These results were not statistically significant. Death Endpoint The incidence rate of all-cause mortality was 11.3% for aspirin and extended-release dipyridamole, 11.0% for aspirin alone, 11.4% for extended-release dipyridamole alone and 12.3% for placebo alone. The differences between the aspirin and extended-release dipyridamole, aspirin alone and extended-release dipyridamole alone treatment groups were not statistically significant.

These incidence rates for aspirin and extended-release dipyridamole and aspirin alone are consistent with previous aspirin studies in stroke and TIA patients. Aspirin

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In studies in which dipyridamole was administered in the feed to mice (up to 111 weeks in males and females) and rats (up to 128 weeks in males and up to 142 weeks in females), there was no evidence of drug-related carcinogenesis. The highest dose administered in these studies (75 mg/kg/day) was, on a mg/m 2 basis, about equivalent to the maximum recommended daily human oral dose (MRHD) in mice and about twice the MRHD in rats. Combinations of dipyridamole and aspirin (1:5 ratio) tested negative in the Ames test, in vivo chromosome aberration tests (in mice and hamsters), oral micronucleus tests (in mice and hamsters) and oral dominant lethal test (in mice).

Aspirin, alone, induced chromosome aberrations in cultured human fibroblasts. Mutagenicity tests of dipyridamole alone with bacterial and mammalian cell systems were negative. Combinations of dipyridamole and aspirin have not been evaluated for effects on fertility and reproductive performance.

There was no evidence of impaired fertility when dipyridamole was administered to male and female rats at oral doses up to 500 mg/kg/day (about 12 times the MRHD on a mg/m 2 basis). A significant reduction in number of corpora lutea with consequent reduction in implantations and live fetuses was, however, observed at 1250 mg/kg (more than 30 times the MRHD on a mg/m 2 basis). Aspirin inhibits ovulation in rats.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility In studies in which dipyridamole was administered in the feed to mice (up to 111 weeks in males and females) and rats (up to 128 weeks in males and up to 142 weeks in females), there was no evidence of drug-related carcinogenesis. The highest dose administered in these studies (75 mg/kg/day) was, on a mg/m 2 basis, about equivalent to the maximum recommended daily human oral dose (MRHD) in mice and about twice the MRHD in rats. Combinations of dipyridamole and aspirin (1:5 ratio) tested negative in the Ames test, in vivo chromosome aberration tests (in mice and hamsters), oral micronucleus tests (in mice and hamsters) and oral dominant lethal test (in mice).

Aspirin, alone, induced chromosome aberrations in cultured human fibroblasts. Mutagenicity tests of dipyridamole alone with bacterial and mammalian cell systems were negative. Combinations of dipyridamole and aspirin have not been evaluated for effects on fertility and reproductive performance.

There was no evidence of impaired fertility when dipyridamole was administered to male and female rats at oral doses up to 500 mg/kg/day (about 12 times the MRHD on a mg/m 2 basis). A significant reduction in number of corpora lutea with consequent reduction in implantations and live fetuses was, however, observed at 1250 mg/kg (more than 30 times the MRHD on a mg/m 2 basis). Aspirin inhibits ovulation in rats.

📄 Patient Package Insert ~3 min read ▾

Patient Information Aspirin and extended-release dipyridamole capsules (as-per-in / ik-sten-did – ree-lees - dahy-pir-i-duh-mohl) Read this Patient Information before you start taking aspirin and extended-release dipyridamole capsules and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What are aspirin and extended-release dipyridamole capsules? Aspirin and extended-release dipyridamole capsules are a prescription medicine that contains aspirin and a medicine that is slowly released in your body, called dipyridamole. Aspirin and extended-release dipyridamole capsules are used to lower the risk of stroke in people who have had a “mini-stroke” (transient ischemic attack or TIA) or stroke due to a blood clot.

It is not known if aspirin and extended-release dipyridamole capsules are safe and effective in children. See “Who should not take aspirin and extended-release dipyridamole capsules?” Who should not take aspirin and extended-release dipyridamole capsules? Do not take aspirin and extended-release dipyridamole capsules if you: • are allergic to any of the ingredients in aspirin and extended-release dipyridamole capsules.

See the end of this leaflet for a list of ingredients in aspirin and extended-release dipyridamole capsules. • are allergic to non-steroidal anti-inflammatory drugs (NSAIDs) • have asthma in combination with runny nose and nasal polyps Do not give aspirin and extended-release dipyridamole capsules to a child or teenager with a viral illness. Reye syndrome, a life-threatening condition, can happen when aspirin (an ingredient in aspirin and extended-release dipyridamole capsules) is used in children and teenagers who have certain viral illnesses.

What should I tell my doctor before using aspirin and extended-release dipyridamole capsules? Before taking aspirin and extended-release dipyridamole capsules, tell your healthcare provider if you: • have stomach ulcers • have a history of bleeding problems • have heart problems • have kidney or liver problems • have low blood pressure • have myasthenia gravis • have any other medical conditions • are pregnant or plan to become pregnant. You should not take aspirin and extended-release dipyridamole capsules during pregnancy without first talking to your healthcare provider.

Tell your healthcare provider right away if you become pregnant while taking aspirin and extended-release dipyridamole capsules. • are breastfeeding or plan to breastfeed. Aspirin and extended-release dipyridamole can pass into your milk. Talk to your healthcare provider about the best way to feed your baby if you take aspirin and extended-release dipyridamole capsules.

Tell your doctor you are taking aspirin and extended-release dipyridamole capsules if you are scheduled to have a stress test for your heart. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Aspirin and extended-release dipyridamole capsules and other medicines may affect each other causing side effects.

Aspirin and extended-release dipyridamole capsules may affect the way other medicines work, and other medicines may affect how aspirin and extended-release dipyridamole capsules work. Especially tell your healthcare provider if you take: • a medicine for high blood pressure, irregular heart beat, or heart failure • acetazolamide [Diamox ® ] • any blood thinner medicines • warfarin sodium [Coumadin ® , Jantoven ® ] • a heparin medicine • anagrelide [Agrylin ® ] • a seizure medicine • a medicine for Alzheimer’s disease • a water pill • methotrexate sodium [Trexall ® ] • aspirin or a non-steroidal anti-inflammatory drug (NSAIDs).

You should not take NSAIDs during treatment with aspirin and extended-release dipyridamole capsules. Using these medicines with aspirin and extended-release dipyridamole capsules can incr… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 26 words ▾

Package/Label Display Panel MAJOR® NDC 0904-7056-99 Unit Dose Aspirin and Extended-Release Dipyridamole Capsules 25 mg/200 mg 20 CAPSULES (5 x 4) Rx only 25mg/200mg carton label

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 00904-7055-61 · Major 00904-7057-61 · Major →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.