DailyMed Label: Dipyridamole

DailyMed Label: Dipyridamole

2024

DailyMed Prescription

Dipyridamole

Dipyridamole

Hikma Pharmaceuticals USA Inc.

NDC: 0641-2569

NDC: 0641-2569

NDC: 0641-2569

Dipyridamole is a coronary vasodilator described as 2,6 bis-(diethanolamino)-4,8 dipiperidino-pyrimido-(5,4-d) pyrimidine. The structural formula is:  C 24 H 40 N 8 O 4                                      MW 504 . 63 Dipyridamole Injection, USP is a sterile, odorless, pale yellow liquid which can be diluted in sodium chloride injection or dextrose injection for intravenous administration. Each mL contains 5 mg dipyridamole, USP, 50 mg polyethylene glycol 600 and 2 mg tartaric acid in Water for Injection, USP. pH 2.2-3.2; hydrochloric acid added for pH adjustment. Structural formula

Dipyridamole Injection is indicated as an alternative to exercise in thallium myocardial perfusion imaging for the evaluation of coronary artery disease in patients who cannot exercise adequately. In a study of about 1100 patients who underwent coronary arteriography and Dipyridamole Injection assisted thallium imaging, the results of both tests were interpreted blindly and the sensitivity and specificity of the dipyridamole thallium study in predicting the angiographic outcome were calculated. The sensitivity of the dipyridamole test (true positive dipyridamole divided by the total number of patients with positive angiography) was about 85%. The specificity (true negative divided by the number of patients with negative angiograms) was about 50%. In a subset of patients who had exercise thallium imaging as well as dipyridamole thallium imaging, sensitivity and specificity of the two tests were almost identical.

The dose of intravenous Dipyridamole Injection as an adjunct to thallium myocardial perfusion imaging should be adjusted according to the weight of the patient. The recommended dose is 0.142 mg/kg/min (0.57 mg/kg total) infused over 4 minutes. Although the maximum tolerated dose has not been determined, clinical experience suggests that a total dose beyond 60 mg is not needed for any patient. Prior to intravenous administration, Dipyridamole Injection should be diluted in at least a 1:2 ratio with sodium chloride injection 0.45%, sodium chloride injection 0.9% or dextrose injection 5% for a total volume of approximately 20 to 50 mL. Infusion of undiluted dipyridamole may cause local irritation. Thallium-201 should be injected within 5 minutes following the 4-minute infusion of dipyridamole. Do not mix Dipyridamole Injection with other drugs in the same syringe or infusion container. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Hypersensitivity to dipyridamole.

See WARNINGS . Oral maintenance theophylline and other xanthine derivatives such as caffeine may abolish the coronary vasodilatation induced by intravenous Dipyridamole Injection administration. This could lead to a false negative thallium imaging result (see  CLINICAL PHARMACOLOGY   –    Mechanism of Action ). Myasthenia gravis patients receiving therapy with cholinesterase inhibitors may experience worsening of their disease in the presence of dipyridamole. In studies in which dipyridamole was administered in the feed at doses of up to 75 mg/kg/day (9.4 times* the maximum recommended daily human oral dose) in mice (up to 128 weeks in males and up to 142 weeks in females) and rats (up to 111 weeks in males and females), there was no evidence of drug-related carcinogenesis. 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 (63 times* the maximum recommended daily human oral dose). A significant reduction in number of corpora lutea with consequent reduction in implantations and live fetuses was, however, observed at 1250 mg/kg/day.     * Calculation based on assumed body weight of 50 kg. Reproduction studies performed in mice and rats at daily oral doses of up to 125 mg/kg (15.6 times* the maximum recommended daily human oral dose) and in rabbits at daily oral doses of up to 20 mg/kg (2.5 times* the maximum recommended daily human oral dose) have revealed no evidence of impaired embryonic development 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 responses, this drug should be used during pregnancy only if clearly needed.     * Calculation based on assumed body weight of 50 kg. Dipyridamole is excreted in human milk. Safety and effectiveness in pediatric patients have not been established.

Adverse reaction information concerning intravenous Dipyridamole Injection is derived from a study of 3911 patients in which intravenous dipyridamole was used as an adjunct to thallium myocardial perfusion imaging and from spontaneous reports of adverse reactions and the published literature.

Oral maintenance theophylline and other xanthine derivatives such as caffeine may abolish the coronary vasodilatation induced by intravenous Dipyridamole Injection administration. This could lead to a false negative thallium imaging result (see  CLINICAL PHARMACOLOGY   –    Mechanism of Action ). Myasthenia gravis patients receiving therapy with cholinesterase inhibitors may experience worsening of their disease in the presence of dipyridamole.

Dipyridamole Injection, USP is available in :     10 mL (50 mg / 10 mL) SINGLE DOSE vial packaged in 5s (NDC 0641-2569-44) PROTECT FROM LIGHT: Keep covered in carton until time of use. Store between 15° to 25°C (59° to 77°F). Avoid freezing. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. For Product Inquiry call 1-877-845-0689. Manufactured by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 Revised December 2019 462-341-03

In a study of 10 patients with angiographically normal or minimally stenosed (less than 25% luminal diameter narrowing) coronary vessels, Dipyridamole Injection in a dose of 0.56 mg/kg infused over 4 minutes resulted in an average fivefold increase in coronary blood flow velocity compared to resting coronary flow velocity (range 3.8 to 7 times resting velocity). The mean time to peak flow velocity was 6.5 minutes from the start of the 4-minute infusion (range 2.5 to 8.7 minutes). Cardiovascular responses to the intravenous administration of Dipyridamole Injection when given to patients in the supine position include a mild but significant increase in heart rate of approximately 20% and mild but significant decreases in both systolic and diastolic blood pressure of approximately 2-8%, with vital signs returning to baseline values in approximately 30 minutes. Dipyridamole is a coronary vasodilator in man. The mechanism of vasodilation has not been fully elucidated, but may result from inhibition of uptake of adenosine, an important mediator of coronary vasodilation. The vasodilatory effects of dipyridamole are abolished by administration of the adenosine receptor antagonist theophylline. How dipyridamole-induced vasodilation leads to abnormalities in thallium distribution and ventricular function is also uncertain but presumably represents a “steal” phenomenon in which relatively intact vessels dilate and sustain enhanced flow, leaving reduced pressure and flow across areas of hemodynamically important coronary vascular constriction. Plasma dipyridamole concentrations decline in a triexponential fashion following intravenous infusion of dipyridamole, with half-lives averaging 3-12 minutes, 33-62 minutes and 11.6-15 hours. Two minutes following a 0.568 mg/kg dose of Dipyridamole Injection administered as a 4-minute infusion, the mean dipyridamole serum concentration is 4.6 ± 1.3 mcg/mL. The average plasma protein binding of dipyridamole is approximately 99%, primarily to α 1 -glycoprotein. Dipyridamole is metabolized in the liver to the glucuronic acid conjugate and excreted with the bile. The average total body clearance is 2.3-3.5 mL/min/kg, with an apparent volume of distribution at steady state of 1-2.5 L/kg and a central apparent volume of 3-5 liters.

NDC 0641- 2569 -41        Rx only Dipyridamole Injection, USP 50 mg per 10 mL (5 mg/mL) For Intravenous use in Myocardial Imaging ONLY DILUTE BEFORE USE 10 mL Single Dose Vial NDC 0641- 2569 -44        Rx only Dipyridamole Injection, USP 50 mg per 10 mL (5 mg/mL) For Intravenous use in Myocardial Imaging ONLY DILUTE BEFORE USE 5 x 10 mL Single Dose Vials vial sp