Persantine (dipyridamole 75 mg) Dailymed

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.
Stress Testing with Intravenous Dipyridamole and Other Adenosinergic Agents: Clinical experience suggests that patients being treated with PERSANTINE tablets who also require pharmacological stress testing with intravenous dipyridamole or other adenosinergic agents (e.g. adenosine, regadenoson) should interrupt PERSANTINE tablets for 48 hours prior to stress testing.
Intake of PERSANTINE tablets within 48 hours prior to stress testing with intravenous dipyridamole or other adenosinergic agents may increase the risk for cardiovascular side effects of these agents and may impair the sensitivity of the test.

Laboratory Tests

Dipyridamole has been associated with elevated hepatic enzymes.

Drug Interactions

No pharmacokinetic drug-drug interaction studies were conducted with Persantine^® (dipyridamole USP) tablets. The following information was obtained from the literature.
Adenosinergic agents (e.g., adenosine, regadenoson): Dipyridamole has been reported to increase the plasma levels and cardiovascular effects of adenosine. Adjustment of adenosine dosage may be necessary. Dipyridamole also increases the cardiovascular effects of regadenoson, an adenosine A2A-receptor agonist. The potential risk of cardiovascular side effects with intravenous adenosinergic agents may be increased during the testing period when dipyridamole is not held 48 hours prior to stress testing.
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).

Pregnancy

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 ½, 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, PERSANTINE tablets should be used during pregnancy only if clearly needed.

Nursing Mothers

As dipyridamole is excreted in human milk, caution should be exercised when PERSANTINE 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 PERSANTINE tablets initial side effects usually disappear. The following reactions in Table 1 were reported in two heart valve replacement trials comparing PERSANTINE tablets and warfarin therapy to either warfarin alone or warfarin and placebo:

Table 1 Adverse Reactions Reported in 2 Heart Valve Replacement Trials

Adverse Reaction	PERSANTINETablets / Warfarin	Placebo / Warfarin
Number 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 Persantine® (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 75-100 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

PERSANTINE tablets are available as round, orange, sugar-coated tablets of 25 mg, 50 mg and 75 mg coded BI/17, BI/18 and BI/19, respectively.
They are available in bottles of 100 tablets as indicated below: 25 mg Tablets        (NDC 0597-0017-01) 50 mg Tablets        (NDC 0597-0018-01) 75 mg Tablets        (NDC 0597-0019-01)

STORAGE AND HANDLING SECTION

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.

Address medical inquiries to: http://us.boehringer-ingelheim.com, (800) 542-6257 or (800) 459-9906 TTY.
Distributed by: Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877 USA
Product and trademark licensed from: Boehringer Ingelheim International GmbH
©Copyright Boehringer Ingelheim International GmbH 2019, ALL RIGHTS RESERVED
OT1500CL172019
Revised: December, 2019

Package Label.principal Display Panel

Persantine (dipyridamole usp) Tablets NDC:0597-0017-01

Package Label.principal Display Panel

Persantine (dipyridamole usp) Tablets NDC:0597-0018-01

Package Label.principal Display Panel

Persantine (dipyridamole usp) Tablets NDC:0597-0019-01