Dipyridamole

B01A - Antithrombotic agents ATC B01AC07 Small molecule approved 1961 Oral Parenteral Natural product

JFDA label: Antiplate-75 Tablets

Mechanism of Action

Inhibitor of Equilibrative nucleoside transporter 1 — Equilibrative nucleoside transporter 1 inhibitor; Inhibitor of 3',5'-cyclic phosphodiesterase — 3',5'-cyclic phosphodiesterase inhibitor

Target	Action	Gene / class
3',5'-cyclic phosphodiesterase efficacy	INHIBITOR
Equilibrative nucleoside transporter 1 efficacy	INHIBITOR	SLC29A1

Indications

Approved

IV
Oral

Off-label

Stroke (prevention, in combination with aspirin)

Contraindications

Source: Lexicomp

Hypersensitivity to dipyridamole or any component of the formulation According to the American Society of Nuclear Cardiology (ASNC) the following are additional contraindications for dipyridamole stress testing (ASNC [Henzlova 2016]): Bronchospastic lung disease with ongoing wheezing or history of significant reactive airway disease Absolute
ingestion of caffeinated foods or beverages within the last 12 hours Absolute
systolic BP 200 mm Hg or diastolic BP >110 mm Hg) Absolute
unstable angina, acute coronary syndrome, or myocardial infarction within 2 to 4 days. Relative contraindications include: Heart rate Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (6)

Very Common Exacerbation of angina pectoris

Common altered blood pressure · ECG abnormality · hypertension

Not Known Angina pectoris · flushing

Nervous system disorders (3)

Common Pain

Not Known Dizziness · headache

Hepatobiliary disorders (1)

Not Known Hepatic insufficiency

Gastrointestinal disorders (3)

Not Known Abdominal distress · diarrhea · vomiting

Skin and subcutaneous tissue disorders (2)

Not Known pruritus · Skin rash

Other (17)

Not Known Alopecia · arthritis · cholelithiasis · dyspepsia · fatigue · Frequency not always defined · hepatitis · hypersensitivity reaction · hypotension · laryngeal edema · malaise · myalgia · nausea · palpitations · paresthesia · tachycardia · thrombocytopenia

Respiratory, thoracic and mediastinal disorders (1)

Common Dyspnea

Dosing

Source: Lexicomp

Adjunctive therapy for prophylaxis of thromboembolism with cardiac valve replacement: Oral: 75 to 100 mg 4 times/day Evaluation of coronary artery disease: IV: 0.56 mg/kg over 4 minutes; maximum dose: 70 mg (ASNC [Henzlova 2016]) Following completion of dipyridamole infusion, inject radiotracer (eg, thallium-201) in 3 to 5 minutes (ASNC [Henzlova 2016]). Note: To reverse complications and side effects of dipyridamole, aminophylline (50 to 250 mg IV push over 30 to 60 seconds given at least 1 minute after the radiotracer injection) should be available for urgent/emergent use. Obesity: Dosing for patients who are obese or morbidly obese is not established; in these patients, it is customary to use doses up to the weight of 125 kg (ASNC [Henzlova 2016]).

(For additional information see "Dipyridamole: Pediatric drug information") Adjunctive therapy for prophylaxis of thromboembolism with cardiac valve replacement: Oral: Children ≥12 years: Refer to adult dosing.

Refer to adult dosing.

No dosage adjustment provided in manufacturer’s labeling. Hemodialysis: Not dialyzable (NCS/SCCM [Frontera 2016])

No dosage adjustment provided in manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

Cardiovascular disease

Use with caution in patients with hypotension, unstable angina, and/or recent MI; may enhance exercise induced myocardial ischemia in patients with chronic stable angina.

Hepatic impairment

Use with caution in patients with hepatic impairment. Concurrent drug therapy issues:

Antiplatelet agents/anticoagulants

Use with caution in patients on other antiplatelet agents or anticoagulation. Dosage form specific issues:

Injection

Severe adverse reactions have occurred rarely with IV administration. Use the IV form with caution in patients with bronchospastic disease or unstable angina. Have aminophylline ready in case of urgency or emergency with IV use.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies.

Lactation

Dipyridamole is excreted in breast milk. The manufacturer recommends that caution be exercised when administering dipyridamole to nursing women.

LactMed: monitor the infant.

Monitoring

Clinical pearl	IV: During stress perfusion imaging, monitor blood pressure, heart rate, ECG, respiration. Monitor for signs of poor perfusion (pallor, cyanosis, cold skin) (ASNC [Henzlova 2016])

Chemistry & Properties

Formula	C24H40N8O4
Molecular weight	504.64 g/mol
IUPAC name	2-[[2-[bis(2-hydroxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-6-yl]-(2-hydroxyethyl)amino]ethanol
CAS	58-32-2
PubChem CID	3108
InChIKey	`IZEKFCXSFNUWAM-UHFFFAOYSA-N`
logP	-0.02 (XLogP 0.7)
Polar surface area	145.44 Å²
H-bond acceptors / donors	12 / 4
Drug-likeness (QED)	0.31
Lipinski violations	2

SMILES

OCCN(CCO)c1nc(N2CCCCC2)c2nc(N(CCO)CCO)nc(N3CCCCC3)c2n1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes (logBB 0.0)

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Inhibitor	—

Receptor binding (top 3)

Target	Action	Affinity
Equilibrative nucleoside transporter 1 (SLC29A1)	Inhibitor	pKi 8.8
Plasma membrane monoamine transporter (SLC29A4)	Inhibitor	pKi 5.9
phosphodiesterase 8A (PDE8A)	Inhibitor	pIC50 5.1

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)ENT1 (Inhibitor)ENT2 (Inhibitor)MATE1 (Inhibitor)MATE2 (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)OCT2 (Inhibitor)OCTN1 (Inhibitor)P-gp (Inhibitor)BCRP (Substrate)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Abciximab	major
Acalabrutinib	major
Apixaban	major
Ardeparin	major
Argatroban	major
Avapritinib	major
Betrixaban	major
Cabozantinib	major
Cangrelor	major
Caplacizumab	major
Dalteparin	major
Danaparoid	major
Dasatinib	major
Deferasirox	major
Defibrotide	major
Desirudin	major
Drotrecogin alfa	major
Edoxaban	major
Enoxaparin	major
Eptifibatide	major
Fondaparinux	major
Ibritumomab tiuxetan	major
Ibrutinib	major
Inotersen	major
Lepirudin	major
Omacetaxine mepesuccinate	major
Panobinostat	major
Ponatinib	major
Prasugrel	major
Ramucirumab	major
Regorafenib	major
Riociguat	major
Rivaroxaban	major
Tinzaparin	major
Tipranavir	major
Tirofiban	major
Tositumomab	major
Tositumomab (I-131)	major
Trastuzumab emtansine	major
Vorapaxar	major

Showing 40 of 100+.

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
perazodin	Tablet 75 mg	30 tab	JAWEDA INT. DRUD STORE	2.410
Antiplate-75 Tablets	Tablet 75 mg	50 tab pack varies	The Arab Pharmaceutical Manufacturing PSC/Salt	3.500
Antiplate-75 Tablets	Tablet 75 mg	1000 tab pack varies	The Arab Pharmaceutical Manufacturing PSC/Salt	63.000