DIPYRIDAMOLE

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: C 24 H 40 N 8 O 4 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. structured formula for dipyridamole

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

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.

Hypersensitivity to dipyridamole and any of the other components.

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 1 Adverse Reactions Reported in 2 Heart Valve Replacement Trials Adverse Reaction Dipyridamole Tablets/ Placebo/ Warfarin 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 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.

No pharmacokinetic drug-drug interaction studies were conducted with dipyridamole 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 A 2A -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.

STORAGE Store at 20°C to 25°C (68°F to 77°F) [ See USP Controlled Room Temperature ]. Keep out of reach of children. Dispense in a tight, light-resistant container. Package insert available at www.zydususa.com/products or call 1-877-993-8779.