DIPYRIDAMOLE

Main information

  • Trade name:
  • DIPYRIDAMOLE- dipyridamole tablet, film coated
  • Composition:
  • DIPYRIDAMOLE 25 mg
  • Administration route:
  • ORAL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • DIPYRIDAMOLE- dipyridamole tablet, film coated
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • Dipyridamole tablets are indicated as an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement. Hypersensitivity to dipyridamole and any of the other components.
  • Product summary:
  • Dipyridamole Tablets USP, 25 mg are light yellow, round, biconvex, film-coated tablets debossed with ‘ZE 43’ on one side and plain on the other side are supplied as follows: NDC 65841-662-01 in bottle of 100 tablets NDC 65841-662-05 in bottle of 500 tablets NDC 65841-662-10 in bottle of 1000 tablets NDC 65841-662-30 in blister of 100 tablets Dipyridamole Tablets USP, 50 mg are light yellow, round, biconvex, beveled-edge, film-coated tablets debossed with ‘ZE 49’ on one side and plain on the other side are supplied as follows: NDC 65841-663-01 in bottle of 100 tablets NDC 65841-663-05 in bottle of 500 tablets NDC 65841-663-10 in bottle of 1000 tablets NDC 65841-663-30 in blister of 100 tablets Dipyridamole Tablets USP, 75 mg are light yellow, round, biconvex, beveled-edge, film-coated tablets debossed with ‘ZE 50’ on one side and plain on the other side are supplied as follows: NDC 65841-664-01 in bottle of 100 tablets NDC 65841-664-05 in bottle of 500 tablets NDC 65841-664-10 in bottle of 1000 tablets NDC 65841-664-30 in blister of 100 tablets Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep out of reach of children. Dispense in a tight, light-resistant container. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. Manufactured by: Cadila Healthcare Ltd. Ahmedabad, India Manufactured by: Cadila Healthcare Ltd. Baddi, India Rev.: 09/11 Rivision Date : 2012/03/22

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 65841-662-01, 65841-662-05, 65841-662-10, 65841-662-30, 65841-663-01, 65841-663-05, 65841-663-10, 65841-663-30, 65841-664-01, 65841-664-05, 65841-664-10, 65841-664-30
  • Last update:
  • 28-05-2019

Summary of Product characteristics: dosage, interactions, side effects

DIPYRIDAMOLE- dipyridamole tablet, film coated

Cadila Healthcare Limited

----------

Dipyridamole Tablets, USP

DESCRIPTION

Dipyridamole 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:

H N O

Mol. Wt. 504.63

Dipyridamole, USP is intensely yellow crystalline powder or needles. It is very soluble in methanol, in

alcohol, and in chloroform; slightly soluble in water; very slightly soluble in acetone and in ethyl

acetate.

Each dipyridamole tablet intended for oral administration contains 25 mg or 50 mg or 75 mg of

dipyridamole. In addition, each tablet contains the following inactive ingredients: corn starch,

hypromellose, iron oxide yellow, 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 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 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 tablets

and warfarin ranged from 1.2 to 1.8%. In three additional studies involving 392 patients taking

dipyridamole 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 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 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 to 1.9

mcg/mL). This inhibition results in an increase in local concentrations of adenosine which acts on the

platelet A -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.

In man the same qualitative hemodynamic effects have been observed.

Pharmacokinetics and Metabolism:

Following an oral dose of dipyridamole tablets, the average time to peak concentration is about 75

minutes. The decline in plasma concentration following a dose of dipyridamole 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 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.

PRECAUTIONS

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 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/m 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/m 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 basis).

Pregnancy:

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

, 2 and 25 times the maximum

recommended daily human oral dose, respectively, on a mg/m 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 tablets should be used during pregnancy only if clearly needed.

Nursing Mothers:

As dipyridamole is excreted in human milk, caution should be exercised when dipyridamole 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 tablets initial side effects usually disappear. The following reactions in Table 1 were

reported in two heart valve replacement trials comparing dipyridamole tablets and warfarin therapy to

either warfarin alone or warfarin and placebo:

Table 1Adverse Reactions Reported in 2 Heart Valve Replacement Trials

Adverse Reaction

Dipyridamole Tablets/

Warfarin

Placebo/

Warfarin

Number of patients

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 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 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, 25 mg are light yellow, round, biconvex, film-coated tablets debossed with

‘ZE 43’ on one side and plain on the other side are supplied as follows:

NDC 65841-662-01 in bottle of 100 tablets

NDC 65841-662-05 in bottle of 500 tablets

NDC 65841-662-10 in bottle of 1000 tablets

NDC 65841-662-30 in blister of 100 tablets

Dipyridamole Tablets USP, 50 mg are light yellow, round, biconvex, beveled-edge, film-coated tablets

debossed with ‘ZE 49’ on one side and plain on the other side are supplied as follows:

NDC 65841-663-01 in bottle of 100 tablets

NDC 65841-663-05 in bottle of 500 tablets

NDC 65841-663-10 in bottle of 1000 tablets

NDC 65841-663-30 in blister of 100 tablets

Dipyridamole Tablets USP, 75 mg are light yellow, round, biconvex, beveled-edge, film-coated tablets

debossed with ‘ZE 50’ on one side and plain on the other side are supplied as follows:

NDC 65841-664-01 in bottle of 100 tablets

NDC 65841-664-05 in bottle of 500 tablets

NDC 65841-664-10 in bottle of 1000 tablets

NDC 65841-664-30 in blister of 100 tablets

Storage:

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep out of reach of

children.

Dispense in a tight, light-resistant container.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-

800-FDA-1088.

Manufactured by:

Cadila Healthcare Ltd.

Ahmedabad, India

Manufactured by:

Cadila Healthcare Ltd.

Baddi, India

Rev.: 09/11

Rivision Date : 2012/03/22

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 65841-662-01 in bottle of 100 tablets

Dipyridamole Tablets USP, 25 mg

R only

100 tablets

ZYDUS

NDC 65841-663-01 in bottle of 100 tablets

Dipyridamole Tablets USP, 50 mg

R only

100 tablets

ZYDUS

NDC 65841-664-01 in bottle of 100 tablets

Dipyridamole Tablets USP, 75 mg

R only

100 tablets

ZYDUS

DIPYRIDAMOLE

dipyridamole tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 58 41-6 6 2

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DIPYRIDAMO LE (UNII: 6 4ALC7F9 0 C) (DIPYRIDAMOLE - UNII:6 4ALC7F9 0 C)

DIPYRIDAMOLE

25 mg

Inactive Ingredients

Ingredient Name

Stre ng th

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

PO VIDO NE (UNII: FZ9 8 9 GH9 4E)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

STARCH, CO RN (UNII: O8 232NY3SJ)

Product Characteristics

Color

YELLOW (LIGHT YELLOW)

S core

no sco re

S hap e

ROUND (ROUND)

S iz e

6 mm

Flavor

Imprint Code

ZE;43

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date Marketing End Date

1

NDC:6 58 41-6 6 2-0 1 10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

2

NDC:6 58 41-6 6 2-0 5 50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

3

NDC:6 58 41-6 6 2-10

10 0 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

4

NDC:6 58 41-6 6 2-30

10 in 1 CARTON

0 5/22/20 0 8

4

10 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 40 8 74

0 5/22/20 0 8

DIPYRIDAMOLE

dipyridamole tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 58 41-6 6 3

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DIPYRIDAMO LE (UNII: 6 4ALC7F9 0 C) (DIPYRIDAMOLE - UNII:6 4ALC7F9 0 C)

DIPYRIDAMOLE

50 mg

Inactive Ingredients

Ingredient Name

Stre ng th

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

PO VIDO NE (UNII: FZ9 8 9 GH9 4E)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

STARCH, CO RN (UNII: O8 232NY3SJ)

Product Characteristics

Color

YELLOW (LIGHT YELLOW)

S core

no sco re

S hap e

ROUND (ROUND)

S iz e

Flavor

Imprint Code

ZE;49

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date Marketing End Date

1

NDC:6 58 41-6 6 3-30

10 in 1 CARTON

0 5/22/20 0 8

1

10 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

2

NDC:6 58 41-6 6 3-0 1 10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

3

NDC:6 58 41-6 6 3-0 5 50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

4

NDC:6 58 41-6 6 3-10

10 0 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 40 8 74

0 5/22/20 0 8

DIPYRIDAMOLE

dipyridamole tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 58 41-6 6 4

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DIPYRIDAMO LE (UNII: 6 4ALC7F9 0 C) (DIPYRIDAMOLE - UNII:6 4ALC7F9 0 C)

DIPYRIDAMOLE

75 mg

Inactive Ingredients

Ingredient Name

Stre ng th

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

HYPRO MELLO SES (UNII: 3NXW29 V3WO)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

PO LYETHYLENE GLYCO L, UNSPECIFIED (UNII: 3WJQ0 SDW1A)

PO VIDO NE (UNII: FZ9 8 9 GH9 4E)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

STARCH, CO RN (UNII: O8 232NY3SJ)

Product Characteristics

Color

YELLOW (LIGHT YELLOW)

S core

no sco re

S hap e

ROUND (ROUND)

S iz e

8 mm

Flavor

Imprint Code

ZE;50

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date Marketing End Date

Cadila Healthcare Limited

1

NDC:6 58 41-6 6 4-30

10 in 1 CARTON

0 5/22/20 0 8

1

10 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

2

NDC:6 58 41-6 6 4-0 1 10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

3

NDC:6 58 41-6 6 4-0 5 50 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

4

NDC:6 58 41-6 6 4-10

10 0 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 5/22/20 0 8

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 40 8 74

0 5/22/20 0 8

Labeler -

Cadila Healthcare Limited (918596198)

Registrant -

Cadila Healthcare Limited (918596198)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Cadila Healthcare

Limite d

9 18 59 6 19 8

ANALYSIS(6 58 41-6 6 2, 6 58 41-6 6 3, 6 58 41-6 6 4) , MANUFACTURE(6 58 41-6 6 2, 6 58 41-

6 6 3, 6 58 41-6 6 4)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

CADILA HEALTHCARE

LIMITED

6 776 0 58 58

ANALYSIS(6 58 41-6 6 2, 6 58 41-6 6 3, 6 58 41-6 6 4) , MANUFACTURE(6 58 41-6 6 2,

6 58 41-6 6 3, 6 58 41-6 6 4)

Revised: 12/2018