PERSANTINE Coated tablet Ref.[11063] Active ingredients: Dipyridamole

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:

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.

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.

Dipyridamole has been associated with elevated hepatic enzymes.

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.

Teratogenic Effects

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.

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

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