NDC 64980-133 Dipyridamole

Dipyridamole

NDC Product Information

Dipyridamole with NDC 64980-133 is a a human prescription drug product labeled by Rising Pharmaceuticals, Inc.. The generic name of Dipyridamole is dipyridamole. The product's dosage form is tablet, film coated and is administered via oral form.

Labeler Name: Rising Pharmaceuticals, Inc.

Dosage Form: Tablet, Film Coated - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Dipyridamole Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • DIPYRIDAMOLE 25 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • STARCH, CORN (UNII: O8232NY3SJ)
  • HYDROXYPROPYL CELLULOSE (1600000 WAMW) (UNII: RFW2ET671P)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • POVIDONE (UNII: FZ989GH94E)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Decreased Platelet Aggregation - [PE] (Physiologic Effect)
  • Platelet Aggregation Inhibitor - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Rising Pharmaceuticals, Inc.
Labeler Code: 64980
FDA Application Number: ANDA040733 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 08-05-2007 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Information for Patients

Dipyridamole

Dipyridamole is pronounced as (dye peer id' a mole)

Why is dipyridamole medication prescribed?
Dipyridamole is used with other drugs to reduce the risk of blood clots after heart valve replacement. It works by preventing excessive blood clotting....
[Read More]

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Dipyridamole Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

Prescribing Information

Rx only Manufactured for: Rising Pharmaceuticals, Inc., Allendale, NJ 07401 USA Manufactured by:Murty Pharmaceuticals, Inc.,Lexington, KY 40509 USAIssued: November 2006 P112-00

Description

Dipyridamole USP is a platelet inhibitor 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 odorless yellow crystalline powder, having a bitter taste. It is soluble in dilute acids, methanol and chloroform, and practically
insoluble in water.Dipyridamole USP tablets for oral administration contain:Active Ingredient TABLETS 25 mg, 50 mg, and 75 mg: dipyridamole USP 25 mg, 50 mg and 75 mg, respectively.Inactive Ingredients TABLETS 25 mg, 50 mg, and 75 mg: corn starch, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, polyethylene glycol, povidone, and titanium dioxide.

Clinical Pharmacology

It is believed that platelet reactivity and interaction with prosthetic cardiac valve surfaces, resulting in abnormally shortened platelet survival time, is a
significant factor in thromboembolic complications occurring in connection with prosthetic heart valve replacement.Dipyridamole USP tablets have been found to lengthen abnormally shortened platelet survival time in a dose-dependent manner.In three randomized controlled clinical trials involving 854 patients who had undergone surgical placement of a prosthetic heart valve, dipyridamole
USP tablets, in combination with warfarin, decreased the incidence of postoperative thromboembolic events by 62 to 91 % compared to warfarin treatment alone. The incidence
of thromboembolic events in patients receiving the combination of dipyridamole USP tablets and warfarin ranged from 1.2 to 1.8%. In three additional studies involving
392 patients taking dipyridamole USP tablets and coumarin-like anticoagulants, the incidence of thromboembolic events ranged from 2.3 to 6.9%.In these trials, the coumarin anticoagulant was begun between 24 hours and 4 days postoperatively, and the dipyridamole USP tablets were begun between 24 hours and 10 days postoperatively. The length of follow-up in these trials varied from 1 to 2 years.Dipyridamole USP tablets do not influence prothrombin time or activity measurements when administered with warfarin.

Mechanism Of Action

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 (0.5-1.9 μg/mL). This inhibition results in an increase in local concentrations of adenosine which acts on the platelet A2-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).

Hemodynamics

In dogs intraduodenal doses of dipyridamole of 0.5 to 4.0 mg/kg produced dose-related decreases in systemic and coronary vascular resistance leading to decreases in systemic blood pressure and increases in coronary blood flow. Onset of action was in about 24 minutes and effects persisted for about 3 hours. Similar effects were observed following IV dipyridamole USP in doses ranging from 0.025 to 2.0 mg/kg. In man the same qualitative hemodynamic effects have been observed. However, acute intravenous administration of dipyridamole USP may worsen
regional myocardial perfusion distal to partial occlusion of coronary arteries.

Pharmacokinetics And Metabolism

Following an oral dose of dipyridamole USP tablets, the average time to peak concentration is about 75 minutes. The decline in plasma concentration
following a dose of Dipyridamole USP tablets fits a two-compartment model. The alpha half-life (the initial decline following peak concentration) is approximately 40 minutes. The beta half-life (the terminal decline in plasma concentration) is approximately 10 hours. Dipyridamole is highly bound to plasma proteins. It is metabolized in the liver where it is conjugated as a glucuronide and excreted with the bile.

Indications And Usage

Dipyridamole USP tablets are indicated as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement.

Contraindications

Hypersensitivity to dipyridamole and any of the other components.

General

Coronary Artery Disease: Dipyridamole has a vasodilatory effect and should be used with caution in patients with severe coronary artery disease (e.g., unstable angina or recently sustained myocardial infarction). Chest pain may be aggravated in patients with underlying coronary artery disease who are receiving dipyridamole. Hepatic Insufficiency: Elevations of hepatic enzymes and hepatic failure have been reported in association with dipyridamole administration. Hypotension: Dipyridamole should be used with caution in patients with hypotension since it can produce peripheral vasodilation.

Laboratory Tests

Dipyridamole has been associated with elevated hepatic enzymes.

Drug Interactions

No pharmacokinetic drug-drug interaction studies were conducted with dipyridamole USP tablets. The following information was obtained from the literature. Adenosine: Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Cholinesterase Inhibitors: Dipyridamole may counteract the anticholinesterase effect of cholinesterase inhibitors, thereby potentially aggravating myasthenia gravis.

Carcinogenesis, 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/m2 basis, about equivalent to the maximum recommended daily human oral dose (MRHD) in mice and about twice the MRHD in rats. Mutagenicity tests of dipyridamole with bacterial and mammalian cell systems were negative. 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/m2 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/m2 basis).

Teratogenic Effects: Pregnancy Category B

Reproduction studies have been performed in mice, rabbits and rats at oral dipyridamole doses of up to 125 mg/kg, 40 mg/kg and 1000 mg/kg, respectively (about 1 1/2, 2 and 25 times the maximum recommended daily human oral dose, respectively, on a mg/m2 basis) and have revealed no evidence of harm to the fetus due to dipyridamole. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, dipyridamole USP should be used during pregnancy only if clearly needed.

Nursing Mothers

As dipyridamole is excreted in human milk, caution should be exercised when dipyridamole USP tablets are administered to a nursing woman.

Pediatric Use

Safety and effectiveness in the pediatric population below the age of 12 years have not been established.

Adverse Reactions

Adverse reactions at therapeutic doses are usually minimal and transient. On long-term use of dipyridamole USP tablets initial side effects usually disappear. The following reactions in Table 1 were reported in two heart valve replacement trials comparing dipyridamole USP tablets and warfarin therapy to either warfarin alone or warfarin and placebo:   Table 1 Adverse Reactions Reported in 2 Heart Valve Replacement TrialsAdverseReactionTablets/WarfarinPlacebo/WarfarinNumber of patients 147 170 Dizziness 13.6% 8.2% Abdominal distress 6.1% 3.5% Headache 2.3% 0.0% Rash 2.3% 1.1% Other reactions from uncontrolled studies include diarrhea, vomiting, flushing and pruritus. In addition, angina pectoris has been reported rarely and there have been rare reports of liver dysfunction. On those uncommon occasions when adverse reactions have been persistent or intolerable, they have ceased on withdrawal of the medication. When dipyridamole USP tablets were administered concomitantly with warfarin, bleeding was no greater in frequency or severity than that observed when warfarin was administered alone. In rare cases, increased bleeding during or after surgery has been observed. In post-marketing reporting experience, there have been rare reports of hypersensitivity reactions (such as rash, urticaria, severe bronchospasm, and angioedema), larynx edema, fatigue, malaise, myalgia, arthritis, nausea, dyspepsia, paresthesia, hepatitis, thrombocytopenia, alopecia, cholelithiasis, hypotension, palpitation, and tachycardia.

Overdosage

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. Symptomatic treatment is recommended, possibly including a vasopressor drug. Gastric lavage should be considered. Administration of xanthine derivatives (e.g., aminophylline) may reverse the hemodynamic effects of dipyridamole overdose. Since dipyridamole is highly protein bound, dialysis is not likely to be of benefit.

Dosage And Administration

Adjunctive Use in Prophylaxis of Thromboembolism after Cardiac Valve Replacement. The recommended dose is 75 mg to 100 mg four times daily as an adjunct to the usual warfarin therapy. Please note that aspirin is not to be administered concomitantly with coumarin anticoagulants.

How Supplied

Dipyridamole tablets, USP, are available as round, white, filmcoated tablets of 25 mg, 50 mg, and 75 mg coded 81/SL, 82/SL, and 83/SL, respectively.They are available in bottles of 100 tablets as indicated below:25 mg Tablets (NDC 64980-133-01)50 mg Tablets (NDC 64980-134-01)75 mg Tablets (NDC 64980-135-01)They are available in bottles of 1000 tablets as indicated below:25 mg Tablets (NDC 64980-133-10)50 mg Tablets (NDC 64980-134-10)75 mg Tablets (NDC 64980-135-10)

Storage And Handling

STORE AT 25°C (77°F); EXCURSIONS PERMITTED TO 15-30°C (59°-86°F) [SEE USP CONTROLLED ROOM TEMPERATURE]. KEEP OUT OF REACH OF CHILDREN.

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