Dipyridamole Injection - Pharmaceutical Information, Clinical Trials, Detailed Pharmacology, Toxicology
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Dipyridamole Injection - Scientific Information

Manufacture: Fresenius Kabi USA, LLC
Country: Canada
Condition: Myocardial Infarction, Prophylaxis, Radionuclide Myocardial Perfusion Study
Class: Cardiac stressing agents, Platelet aggregation inhibitors, Vasodilators
Form: Liquid solution, Intravenous (IV)
Ingredients: Dipyridamole, polyethylene glycol, tartaric acid, hydrochloric acid, water for Injection

Pharmaceutical Information

Drug Substance

Non-proprietary Name: Dipyridamole
Chemical Name(s): 2,2',2'',2'''-[(4,8- Dipiperidinopyrimido[5,4-d] pyrimidine-2,6- diyl)dinitrilo]tetraethanol
Structural Formula:

Molecular Formula: C24H40N8O4
Molecular Weight: 504.6
Melting Range: 164 - 168°C
Description: A homogeneous yellow crystalline powder, odourless but with a bitter taste. It is soluble in dilute acids, methanol, ethanol and chloroform. In solutiipyridamole is yellow and shows a strong blue-green fluorescence.


Each mL contains: 5 mg dipyridamole, 50 mg polyethylene glycol 600, 2 mg tartaric acid, hydrochloric acid for pH adjustment, in Water for Injection.

Stability and Storage Recommendations

Dipyridamole Injection, USP should be stored at room temperature (15 to 30°C). Protect Dipyridamole Injection from direct light, and avoid freezing.

Parenteral Products

Diluted solutions should be used within 6 hours after mixing. For detailed information regarding dilution, see DOSAGE AND ADMINISTRATION.

As with all parenteral drug products, intravenous admixtures should be inspected visually for clarity, particulate matter, precipitate, discolouration and leakage prior to administration, whenever solution and container permit. Solutions showing haziness, particulate matter, precipitate, discolouration and leakage should not be used. Discard unused portions.

Availability of Dosage Forms

Dipyridamole Injection, USP is available as 5 mg/mL in 10 mL single-dose vials as follows:

C601310 10 mL single-dose vials in packages of 10 vials.



In animal studies, autoradiography in rats shows the liver with the highest concentrations of dipyridamole, with decreasing quantities in the following tissues: adrenal cortex, kidneys, myocardium, pituitary, skeletal muscle, lungs and blood. Twice as much drug is found in the myocardium as in skeletal muscle. Within the myocardium, the largest portion of dipyridamole is intracellular with the sarcolemma fraction containing up to 50%. On the basis of autoradiography, there are only small amounts of placental transfer. The drug does not cross the blood-brain barrier.

Conjugation of dipyridamole with glucuronic acid is the primary pathway of metabolism. In individuals with surgical drainage of the biliary tract, 95% of an intravenous 25 mg dose can be recovered from the bile within 2 hours. Enterohepatic circulation has been demonstrated in both animals and man.


Circulatory Effects

The effects, of endogenous adenosine are potentiated by dipyridamole inhibition of adenosine uptake in erythrocytes and platelets. Since adenosine is involved in physiological regulation of coronary blood flow, the coronary vasodilation induced by dipyridamole may be related to the adenosine-sparing effect of this drug.

Intravenous injection of dipyridamole in the dog causes coronary vasodilation. The threshold dose is 0.01 mg/kg with maximal effects reached by 0.2 mg/kg. A fall in systemic blood pressure, due to peripheral vasodilation, can be detected at a dose of 0.5 mg/kg with variable but not major effects on heart rate. The diastolic pressure decrease is larger than that for systolic pressure. The respiratory rate and depth are slightly increased, probably due to stimulation of carotid sinus chemoreceptors. An oral dose of 2.0 mg/kg in the dog increases coronary blood flow by 246% for 5 hours.

In the presence of aneroid ring constriction of coronary vessels, chronic administration of dipyridamole in dogs, rabbits and pigs increases the number and diameter of collateral coronary vessels. The rate of mortality in these animals is decreased compared to non-drug treated controls. Even in the absence of a chronic hypoxic stimulus, chronic dipyridamole treatment produces greater flow across intercoronary vessels in response to acute ligation of a coronary mainstem artery, compared to controls. When blood flow through ischemic areas was measured in experimentally produced infarctions, acute intravenous dipyridamole has produced both increases and decreases, as well as no change in flow. Intravenous dipyridamole, 10 mg/hr for 6 hours, decreased the size of experimental infarctions in dogs by 76% compared to saline-treated controls.


Acute Toxicity of Dipyridamole, ASA and their Combination
Substance Species Route of Administration LD50
dipyridamole rat
acetylsalicylic acid
dipyridamole/ASA* mouse (male)
mouse (female)
rat (male)
rat (female)
mouse (male)
mouse (female)
rat (male)
rat (female)
3,000 - 5,000
875 - 950

* dipyridamole/ASA mixed in a ratio of 1/5, weight/weight

After administration of dipyridamole, signs of toxicity among the survivors were ataxia and depression, while in those that died, prostration and tonic convulsions were also seen. After ASA, lethargy fluctuating with restlessness, bleeding through the nose and respiratory distress occurred. Some animals died in a prostrate position without any preceding agitation. Symptomatology following administration of the combination dipyridamole/ASA, (1/5), did not differ appreciably from the toxic signs observed with either substance alone.

Subacute intravenous administration of dipyridamole to dogs at levels of 1 and 10 mg/kg/day for 4 weeks did not produce significant signs of toxicity. Oral dipyridamole (20, 40, 60, 80 mg/kg/day) administered for 13 weeks to beagles produced no toxic effect at the low dose but resulted in kidney toxicity with increasing doses. This was manifested by weight loss, increased blood urea and serum creatinine and epithelial nephritis at the high dose. The abnormalities were rapidly reversible upon discontinuation of treatment. When dogs were treated orally for 26 weeks with dipyridamole at doses of 10, 20 and 40 mg/kg/day, only occasional emesis occurred at the high dose level. Hematological, biochemical and urinary analyses were within normal limits. Rats fed dipyridamole in the diet at levels of 25, 75 and 225 mg/kg/day over a period of 27 weeks showed no signs of toxicity.

Treatment of rats for 3 months with the combination dipyridamole/ASA (1/5) at oral doses of 25, 100 and 400 mg/kg resulted in no drug-related toxicity except for a delay in body weight development in the high dose group. In chronic toxicity studies of 6 months duration in rats and dogs, dipyridamole/ASA (1/4) had no toxic effect at doses of 25 and 100 mg/kg in either species. With increasing dose (200 and 400 mg/kg/day), renal and gastrointestinal lesions appeared along with associated biochemical changes. At the high dose in dogs, all animals were dead at 3 months. Control groups of dogs received ASA, 80 and 160 mg/kg/day. The lesions observed were similar to toxic signs in the combination treatment groups except for the nephritis and renal changes seen in the 200 and 400 mg/kg dose groups of dogs.

Two year carcinogenicity studies of dipyridamole in mouse and rat in doses up to 75 mg/kg demonstrated no tumorogenic effect of the drug. The dipyridamole/ASA combination (1/5) also produced no evidence of carcinogenicity in either rats or mice at oral doses up to 450 mg/kg. Mutagenicity assays (cytogenetic, microorganism, dominant lethal and micronucleus tests) of both dipyridamole alone and the dipyridamole/ASA combination (1/15) could not demonstrate any mutagenic potential of these compounds.