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Aspirin and Extended-Release Dipyridamole 25 mg; 200 mg Capsule, 60-count — NDC 42291-0116-60 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 25 mg; 200 mg Capsule, 60-count — NDC 42291-116-60 (Billing 42291-0116-60)

by AvKARE · 60 CAPSULE in 1 BOTTLE

This is a package of 60 capsules of Aspirin and Extended-Release Dipyridamole 25 mg; 200 mg Capsule from AvKARE, marketed since Apr 2017 and currently FDA-listed. It is this product's only package size.

NDC 42291-0116-60
🏷️ FDA NDC (as labeled) 42291-116-60 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Oct 8, 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

NDC database record

One package, one record: these facts belong to NDC 42291-116-60 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
42291 labeler · 116 product · 60 package
Package marketed since
Apr 27, 2017
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
60 EA per package
Barcode (UPC)
0342291116603
FDA record last changed
Oct 8, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 42291-116-60
Product NDC 42291-116
11-digit billing NDC 42291011660
NCPDP billing unit EA — each (per item)
RxCUI 259081
UNII R16CO5Y76E, 64ALC7F90C
UPC 0342291116603
Application # ANDA206392
SPL Set ID c9a73ec9-e468-46a5-b2c1-99f1f1536585
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 2017-04-27
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

GPI-14 85159902206920
GPI class Aspirin-Dipyridamole ER
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
  • GPI-14 (Medi-Span): 85159902206920
  • HICL (First Databank): 012474
  • AHFS class code: 20:12.18.00
  • RxCUI (RxNorm): 259081
Why two NDCs? The FDA registers this code as 42291-116-60 — a 5-3-2 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 product segment → 42291-0116-60. 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
📗 Our plain-language guide HelloPharmacist
  • It lowers your chance of having another stroke. It is for people who have had a TIA (mini-stroke) or an ischemic stroke caused by a clot. It combines two antiplatelet medicines tha...
  • Take one capsule in the morning and one in the evening. Swallow it whole and do not chew it. You can take it with or without food.
  • Headache is the most common side effect, and it often eases as treatment continues. If it is too much, call your prescriber. They may have you take one capsule at bedtime with low-...
  • I get bad headaches since starting. What should I do?
📖 Read our full Aspirin and Extended-Release Dipyridamole guide →

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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
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 · Q2 2026 $1.20 $71.98 / 60 capsules
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
42291-0116-60 You're viewing this Main listing 60 CAPSULE in 1 BOTTLE 2017-04-27 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Aspirin and Extended - Release Dipyridamole Capsules, 25 mg / 200 mg 25 mg/1; 200 mg 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 mgthis 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
Apr 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 / yellow
ShapeCapsule
ImprintAN;596
Size23 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.

🧪 Avoiding an ingredient? See Aspirin and Extended-Release Dipyridamole inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

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

  • UNII 8PJ61P6TS3
    Butyl alcohol is a clear liquid organic solvent derived from petroleum or natural sources. In medicines, it helps dissolve active ingredients and serves as a solvent in liquid formulations and some topical products.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII 35SW5USQ3G
    A synthetic yellow dye used to color medicines. It helps make tablets, capsules, and liquids visually distinct so patients can easily identify their medication.
  • UNII 92RU3N3Y1O
    Dimethicone is a silicone-based oil that acts as an anti-foaming agent and lubricant in medicines. It reduces gas bubbles in liquid formulations and helps coat and protect the stomach lining when ingested.
  • 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 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 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 87Y6436BKR
    Hypromellose phthalate is a plant-derived polymer that forms a protective coating around pills and capsules. It dissolves in the intestines rather than the stomach, helping deliver the medicine to the right place for absorption.
  • 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 ND2M416302
    Isopropyl alcohol is a clear liquid solvent derived from petroleum. In medicines, it dissolves active ingredients and other components, helps the product flow smoothly, and aids in sterilization during manufacturing.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII NX76LV5T8J
    A synthetic plastic polymer made from methacrylic acid and ethyl acrylate. It's used as a coating or binder to control how and where the medicine dissolves in your digestive system.
  • UNII 3WJQ0SDW1A
    Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
  • 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 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • 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 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during 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 C151H8M554
    A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
  • 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 8Z96QXD6UM
    Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.
  • 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.

29 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

LabelerAvKARE
Application holderAMNEAL PHARMACEUTICALS OF NEW YORK LLC
FDA applicationANDA206392 (ANDA)
Labeler code42291
First marketedApr 2017
Product typeHuman Prescription Drug
Portfolio384 products on file

More NDCs from AvKARE labeler code 42291

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 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 68 words ▾

1 INDICATIONS AND USAGE Aspirin and extended-release dipyridamole capsules are 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 capsulesis a combination antiplatelet agent 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 ~1 min read ▾

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) 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.

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 69 words ▾

3 DOSAGE FORMS AND STRENGTHS 25 mg/200 mg capsules with a red opaque cap and a yellow opaque body, filled with light yellow to yellow extended-release dipyridamole pellets and a white to off-white, round, film-coated, biconvex, unscored, plain aspirin tablet. The capsule is imprinted axially with “AN” in yellow ink on the cap and “596” in red ink on the body. Capsule: 25 mg aspirin/200 mg extended-release dipyridamole (3)

⛔ Contraindications 186 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 capsules are contraindicated in patients with known hypersensitivity to any of the product components.

4.2Allergy Aspirin, USP 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, USP may cause severe urticaria, angioedema or bronchospasm.

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

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

4.2Allergy Aspirin, USP 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, USP may cause severe urticaria, angioedema or bronchospasm.

4.3Reye Syndrome Do not use aspirin, USP 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 capsulesincreases the risk of bleeding (5.1) Avoid use in patients with severe hepatic or renal insufficiency (5.2, 5.3) Can cause fetal harm when administered to a pregnant woman, especially in the third trimester (5.4)

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 incidence of intracranial hemorrhage was 0.6% in the aspirin and extended-release dipyridamole group, 0.5% in the extended-release dipyridamole (ER-DP) group, 0.4% in the aspirin (ASA) group and 0.4% 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 incidence of gastrointestinal bleeding was 4.1% in the aspirin and extended-release dipyridamole group, 2.2% in the extended-release dipyridamole group, 3.2% in the aspirin group and 2.1% 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 capsules contain 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) ] .

5.4Pregnancy Because aspirin and extended-release dipyridamole capsules contain aspirin, aspirin and extended-release dipyridamole capsules can cause fetal harm when administered to a pregnant woman. Maternal aspirin use during later stages of pregnancy may cause low birth weight, increased incidence for intracranial hemorrhage in premature infants, stillbirths and neonatal death. Because of the above and because of the known effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the fetal cardiovascular system (closure of the ductus arteriosus), avoid aspirin and extended-release dipyridamole in the third trimester of pregnancy [see Use in Specific Populations (8.1) ] .

Aspirin has been shown to be teratogenic in rats (spina bifida, exencephaly, microphthalmia and coelosomia) and rabbits (congested fetuses, agenesis of skull and upper jaw, generalized edema with malformation of the head and diaphanous skin) at oral doses of 330 mg/kg/day and 110 mg/kg/day, respectively. These doses, which also resulted in a high resorption rate in rats (63% of implantations versus 5% in controls), are, on a mg/m 2 basis, about 66 and 44 times, respectively, the dose of aspirin contained in the maximum recommended daily human dose of aspirin and extended-release dipyridamole.

Reproduction studies with dipyridamole have been performed in mice, rabbits and rats at oral doses of up to 125 mg/kg, 40 mg/kg and 1,000 mg/kg, respectively (about 1½, 2 and 25 times the maximum recommended daily human oral dose, respectively, on a mg/m 2 basis) and have revealed no evidence of harm… [Excerpted — this section continues on DailyMed.]

🤒 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) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or www.avkare.com 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 6,602 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 6,602 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 incidence of adverse events that occurred in 1% or more of patients treated with aspirin and extended-release dipyridamole where the incidence was also 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 Aspirin and Extended-release Dipyridamole ER-DP Alone ASA Alone Placebo Body System/Preferred Term 1,650 1,654 1,649 1,649 Total Number of Patients Total Number (%) of Patients With at Least One On-Treatment Adverse Event 1,319 (80%) 1,305 (79%) 1,323 (80%) 1,304 (79%) Central and Peripheral Nervous System Disorders Headache 647 (39%) 634 (38%) 558 (34%) 543 (33%) Convulsions 28 (2%) 15 (1%) 28 (2%) 26 (2%) Gastrointestinal System Disorders Dyspepsia 303 (18%) 288 (17%) 299 (18%) 275 (17%) Abdominal Pain 289 (18%) 255 (15%) 262 (16%) 239 (14%) Nausea 264 (16%) 254 (15%) 210 (13%) 232 (14%) Diarrhea 210 (13%) 257 (16%) 112 (7%) 161 (10%) Vomiting 138 (8%) 129 (8%) 101 (6%) 118 (7%) Hemorrhage Rectum 26 (2%) 22 (1%) 16 (1%) 13 (1%) Melena 31 (2%) 10 (1%) 20 (1%) 13 (1%) Hemorrhoids 16 (1%) 13 (1%) 10 (1%) 10 (1%) GI Hemorrhage 20 (1%) 5 (0%) 15 (1%) 7 (0%) Body as a Whole - General Disorders Pain 105 (6%) 88 (5%) 103 (6%) 99 (6%) Fatigue 95 (6%) 93 (6%) 97 (6%) 90 (5%) Back Pain 76 (5%) 77 (5%) 74 (4%) 65 (4%) Accidental Injury 42 (3%) 24 (1%) 51 (3%) 37 (2%) Malaise 27 (2%) 23 (1%) 26 (2%) 22 (1%) Asthenia 29 (2%) 19 (1%) 17 (1%) 18 (1%) Syncope 17 (1%) 13 (1%) 16 (1%) 8 (0%) Psychiatric Disorders Amnesia 39 (2%) 40 (2%) 57 (3%) 34 (2%) Confusion 18 (1%) 9 (1%) 22 (1%) 15 (1%) Anorexia 19 (1%) 17 (1%) 10 (1%) 15 (1%) Somnolence 20 (1%) 13 (1%) 18 (1%) 9 (1%) Musculoskeletal System Disorders Arthralgia 91 (6%) 75 (5%) 91 (6%) 76 (5%) Arthritis 34 (2%) 25 (2%) 17 (1%) 19 (1%) Arthrosis 18 (1%) 22 (1%) 13 (1%) 14 (1%) Myalgia 20 (1%) 16 (1%) 11 (1%) 11 (1%) Respiratory System Disorders Coughing 25 (2%) 18 (1%) 32 (2%) 21 (1%) Upper Respiratory Tract Infection 16 (1%) 9 (1%) 16 (1%) 14 (1%) Cardiovascular Disorders, General Cardiac Failure 26 (2%) 17 (1%) 30 (2%) 25 (2%) Pl… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Co-administration with anti-coagulants, 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 Adenosine Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Angiotensin Converting Enzyme (ACE) Inhibitors 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.

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.

7.1Drug Interaction Study Information Obtained From Literature Adenosine Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Angiotensin Converting Enzyme (ACE) Inhibitors 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.

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 bleedin… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy Category D (8.1)

8.1Pregnancy Teratogenic Effects, Pregnancy Category D. [see Warnings and Precautions (5.4) ].

8.2Labor and Delivery Aspirin can result in excessive blood loss at delivery as well as prolonged gestation and prolonged labor. Because of these effects on the mother and because of adverse fetal effects seen with aspirin during the later stages of pregnancy [see Warnings and Precautions (5.4) ] , avoid aspirin and extended-release dipyridamole in the third trimester of pregnancy and during labor and delivery.

8.3Nursing Mothers Both dipyridamole and aspirin are excreted in human milk. Exercise caution when aspirin and extended-release dipyridamole capsules are administered to a nursing woman.

8.4Pediatric Use Safety and effectiveness of aspirin and extended-release dipyridamole in pediatric patients have not been studied. Due to the aspirin component, use of this product in the pediatric population is not recommended [see Contraindications (4.3) ] .

8.5Geriatric Use Of the total number of subjects in ESPS2, 61 percent were 65 and over, while 27 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3) ] .

8.6Patients with Severe Hepatic or Severe Renal Dysfunction Aspirin and extended-release dipyridamole has not been studied in patients with hepatic or renal impairment. Avoid using aspirin containing products, such as aspirin and extended-release dipyridamole in patients with severe hepatic or severe renal (glomerular filtration rate < 10 mL/min) dysfunction [see Warnings and Precautions (5.2, 5.3) and Clinical Pharmacology (12.3) ] .

8.6Patients with Severe Hepatic or Severe Renal Dysfunction Aspirin and extended-release dipyridamole has not been studied in patients with hepatic or renal impairment. Avoid using aspirin containing products, such as aspirin and extended-release dipyridamole in patients with severe hepatic or severe renal (glomerular filtration rate < 10 mL/min) dysfunction [see Warnings and Precautions (5.2, 5.3) and Clinical Pharmacology (12.3) ] .

🤰 Pregnancy 13 words ▾

8.1Pregnancy Teratogenic Effects, Pregnancy Category D. [see Warnings and Precautions (5.4) ].

🧒 Pediatric Use 39 words ▾

8.4Pediatric Use Safety and effectiveness of aspirin and extended-release dipyridamole in pediatric patients have not been studied. Due to the aspirin component, use of this product in the pediatric population is not recommended [see Contraindications (4.3) ] .

🧓 Geriatric Use 73 words ▾

8.5Geriatric Use Of the total number of subjects in ESPS2, 61 percent were 65 and over, while 27 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3) ] .

🆘 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 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.

🧬 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. Dipyridamole Absorption 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). Effect of Food 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.

Distribution 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.

Metabolism and Elimination 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 λz with a half-life of about 15.5 hours. Due to the extended absorption phase of the dipyridamole component, only the terminal phase is apparent from oral treatment with aspirin and extended-release dipyridamole which, in Trial 9.123 was 13.6 hou… [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 111 words ▾

16 HOW SUPPLIED Aspirin and extended-release dipyridamole capsules, 25 mg/200 mg, are available as two piece hard gelatin capsules, with a red opaque cap and a yellow opaque body, filled with light yellow to yellow extended-release dipyridamole pellets and a white to off-white, round, film-coated, biconvex, unscored, plain aspirin tablet. The capsule is imprinted axially with “AN” in yellow ink on the cap and “596” in red ink on the body. Aspirin and extended-release dipyridamole capsules are supplied as follows: Bottles of 60: NDC 42291-116-60 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

Protect from excessive moisture.

📋 Description ~1 min read ▾

11 DESCRIPTION Aspirin and extended-release dipyridamole is a combination antiplatelet agent intended for oral administration. Each hard gelatin capsule contains 200 mg dipyridamole, USP in an extended-release form and 25 mg aspirin USP, as an immediate-release sugar-coated tablet. In addition, each capsule contains the following inactive ingredients: colloidal silicon dioxide, corn starch, hypromellose, hypromellose phthalate, lactose monohydrate, methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol, simethicone, stearic acid, sucrose, talc, tartaric acid, triethyl citrate and triacetin.

Each capsule shell contains D&C Yellow #10, gelatin, iron oxide red, iron oxide yellow, purified water, sodium lauryl sulfate and titanium dioxide. The imprinting inks contain butyl alcohol, D&C Yellow #10, dehydrated alcohol, FD&C Red #40, isopropyl alcohol, povidone, propylene glycol, shellac, sodium hydroxide and titanium dioxide. Dipyridamole, USP Dipyridamole, USP 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, USP is an odorless yellow crystalline substance, having a bitter taste. It is soluble in dilute acids, methanol and chloroform, and is practically insoluble in water. Aspirin, USP The antiplatelet agent aspirin, USP (acetylsalicylic acid) is chemically known as benzoic acid, 2- (acetyloxy)-, and has the following structural formula: Aspirin, USP is an odorless white needle-like crystalline or powdery substance.

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. chem struc DP chem struc ASP

💬 Information for Patients 204 words ▾

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 Inform patients that aspirin is known to be harmful to fetuses and ask the patient to notify them if they are or become pregnant.

Headaches Some patients may experience headaches upon treatment initiation; these are usually transient. In case of intolerable headaches, tell patients to contact their physician. 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.

Manufactured for: AvKARE Pulaski, TN 38478 Mfg. Rev. 12-2015-00 AV 04/17 (P)

🍼 Nursing Mothers 26 words ▾

8.3Nursing Mothers Both dipyridamole and aspirin are excreted in human milk. Exercise caution when aspirin and extended-release dipyridamole capsules are administered to a nursing woman.

🧬 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. Dipyridamole Absorption 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). Effect of Food 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.

Distribution 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.

Metabolism and Elimination 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 λz with a half-life of about 15.5 hours. Due to the extended absorption phase of the dipyridamole component, only the terminal phase is apparent from oral treatment with aspirin and extended-release dipyridamole which, in Trial 9.123 was 13.6 hours.

Special Populations Geriatric Patients: In ESPS2 [see Clinical Studies (14) ] , plasma concentrations (determined as AUC) of dipyridamole in healthy elderly subjects (>65 years) were about 40% higher than in subjects younger than 55 years receiving treatment with aspirin and extended-release dipyridamole. Hepatic Dysfunction: No study has been conducted with aspirin and extended-release dipyridamole in patients with hepatic dysfunction. In a study conducted with an intravenous formulation of dipyridamole, patients with mild to severe hepatic insufficiency showed no change in plasma concentrations of dipyridamole but showed an increase in the pharmacologically inactive monoglucuronide metabolite.

Dipyridamole can be dosed without restriction as long as there is no evidence of hepatic failure. Renal Dysfunction: No study has been conducted with aspirin and extended-release dipyridamole in patients with renal dysfunction. In ESPS2 patients [see Clinical Studies (14) ] , with creatinine clearances ranging from about 15 mL/min to >100 mL/min, no changes were observed in the pharmacokinetics of dipyridamole or its glucuronide metabolite if data were corrected for differences in age.

Aspirin Absorption 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… [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 ~3 min read ▾

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 6,602 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 6,602 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 incidence of adverse events that occurred in 1% or more of patients treated with aspirin and extended-release dipyridamole where the incidence was also 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 Aspirin and Extended-release Dipyridamole ER-DP Alone ASA Alone Placebo Body System/Preferred Term 1,650 1,654 1,649 1,649 Total Number of Patients Total Number (%) of Patients With at Least One On-Treatment Adverse Event 1,319 (80%) 1,305 (79%) 1,323 (80%) 1,304 (79%) Central and Peripheral Nervous System Disorders Headache 647 (39%) 634 (38%) 558 (34%) 543 (33%) Convulsions 28 (2%) 15 (1%) 28 (2%) 26 (2%) Gastrointestinal System Disorders Dyspepsia 303 (18%) 288 (17%) 299 (18%) 275 (17%) Abdominal Pain 289 (18%) 255 (15%) 262 (16%) 239 (14%) Nausea 264 (16%) 254 (15%) 210 (13%) 232 (14%) Diarrhea 210 (13%) 257 (16%) 112 (7%) 161 (10%) Vomiting 138 (8%) 129 (8%) 101 (6%) 118 (7%) Hemorrhage Rectum 26 (2%) 22 (1%) 16 (1%) 13 (1%) Melena 31 (2%) 10 (1%) 20 (1%) 13 (1%) Hemorrhoids 16 (1%) 13 (1%) 10 (1%) 10 (1%) GI Hemorrhage 20 (1%) 5 (0%) 15 (1%) 7 (0%) Body as a Whole - General Disorders Pain 105 (6%) 88 (5%) 103 (6%) 99 (6%) Fatigue 95 (6%) 93 (6%) 97 (6%) 90 (5%) Back Pain 76 (5%) 77 (5%) 74 (4%) 65 (4%) Accidental Injury 42 (3%) 24 (1%) 51 (3%) 37 (2%) Malaise 27 (2%) 23 (1%) 26 (2%) 22 (1%) Asthenia 29 (2%) 19 (1%) 17 (1%) 18 (1%) Syncope 17 (1%) 13 (1%) 16 (1%) 8 (0%) Psychiatric Disorders Amnesia 39 (2%) 40 (2%) 57 (3%) 34 (2%) Confusion 18 (1%) 9 (1%) 22 (1%) 15 (1%) Anorexia 19 (1%) 17 (1%) 10 (1%) 15 (1%) Somnolence 20 (1%) 13 (1%) 18 (1%) 9 (1%) Musculoskeletal System Disorders Arthralgia 91 (6%) 75 (5%) 91 (6%) 76 (5%) Arthritis 34 (2%) 25 (2%) 17 (1%) 19 (1%) Arthrosis 18 (1%) 22 (1%) 13 (1%) 14 (1%) Myalgia 20 (1%) 16 (1%) 11 (1%) 11 (1%) Respiratory System Disorders Coughing 25 (2%) 18 (1%) 32 (2%) 21 (1%) Upper Respiratory Tract Infection 16 (1%) 9 (1%) 16 (1%) 14 (1%) Cardiovascular Disorders, General Cardiac Failure 26 (2%) 17 (1%) 30 (2%) 25 (2%) Platelet, Bleeding and Clotting Disorders Hemorrhage NOS 52 (3%) 24 (1%) 46 (3%) 24 (1%) Epistaxis 39 (2%) 16 (1%) 45 (3%) 25 (2%) Purpura 23 (1%) 8 (0%) 9 (1%) 7 (0%) Neoplasm Neoplasm NOS 28 (2%) 16 (1%) 23 (1%) 20 (1%) Red Blood Cell Disorders Anemia 27 (2%) 16 (1%) 19 (1%) 9 (1%) a Reported by ≥1% of patients during aspirin and extended-release dipyridamole treatment where the incidence was greater than in those treated with placebo.

Note: ER-DP = extended-release dipyridamole 200 mg; ASA = aspirin 25 mg. The dos… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis and Mutagenesis and 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 1,250 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 and Mutagenesis and 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 1,250 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 Patient Information Aspirin (AS-pir-in) and Extended-release Dipyridamole (dye-pir-ID-a-mole) Capsules 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. Aspirin and extended-release dipyridamole capsules can harm your unborn baby, especially if you take it in the last (third) trimester of pregnancy.

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 breast-feeding or plan to breast-feed. Aspirin and extended-release dipyridamole can pass into your milk and may harm your baby.

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 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 works. 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. Using these medicines with aspirin and extended-release dipyridamole capsules can increase your risk of bleeding. a… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 5 words ▾

PRINCIPAL DISPLAY PANEL 25 200

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
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Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
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Who lists this product with the FDA?
AvKARE is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 42291-0094-30 · AvKARE 42291-0125-50 · AvKARE →
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.