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Dipyridamole


General


Pronunciation

(dye peer ID a mole)


Brand Names: U.S.

  • Persantine [DSC]

Indications


Use: Labeled Indications

Oral: Used with warfarin to decrease thrombosis in patients after artificial heart valve replacement

IV: Diagnostic agent in CAD


Contraindications


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; systolic BP <90 mm Hg; uncontrolled hypertension (systolic BP >200 mm Hg or diastolic BP >110 mm Hg); ingestion of caffeinated foods or beverages within the last 12 hours


Dosing and Administration


Dosing: Adult

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]).


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Adjunctive therapy for prophylaxis of thromboembolism with cardiac valve replacement: Oral: Children ≥12 years: Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment provided in manufacturer 's labeling.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling.


Reconstitution

Prior to administration, dilute solution for injection to a ≥1:2 ratio in NS, 1/2NS, or D5W. Total volume should be ~20-50 mL.


Administration

IV: Infuse diluted solution over 4 minutes.

Tablet: Administer with water 1 hour before meals.


Dietary Considerations

Tablet: Should be taken with water 1 hour before meals.


Storage

IV: Store between 15 � �C to 25 � �C (59 � �F to 77 � �F); do not freeze. Protect from light.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 5 mg/mL (2 mL, 10 mL)

Tablet, Oral:

Persantine: 25 mg [DSC], 50 mg [DSC], 75 mg [DSC] [contains fd&c yellow #10 aluminum lake, methylparaben, propylparaben, sodium benzoate]

Generic: 25 mg, 50 mg, 75 mg


Extemporaneously Prepared

A 10 mg/mL oral suspension may be made with tablets and one of three different vehicles (cherry syrup, a 1:1 mixture of Ora-Sweet � � and Ora-Plus � �, or a 1:1 mixture of Ora-Sweet � � SF and Ora-Plus � �). Crush twenty-four 50 mg tablets in a mortar and reduce to a fine powder. Add 20 mL of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well " � and "protect from light " �. Stable for 60 days when stored in amber plastic prescription bottles in the dark at room temperature or refrigerated.

Allen LV and Erickson III MA, "Stability of Baclofen, Captopril, Diltiazem, Hydrochloride, Dipyridamole, and Flecainide Acetate in Extemporaneously Compounded Oral Liquids, " � Am J Health Syst Pharm, 1996, 53:2179-84. [PMID: 8879325]

Compatibility

Stable in 1/2NS, D5W, NS. Do not mix with other drugs in syringe or infusion container.


Drug Interactions

Acetylcholinesterase Inhibitors: Dipyridamole may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Adenosine: Dipyridamole may enhance the adverse/toxic effect of Adenosine. Specifically, cardiovascular effects of adenosine may be enhanced. Adenosine dose reduction may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Consider therapy modification

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

Beta-Blockers: Dipyridamole may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

Regadenoson: Dipyridamole may enhance the adverse/toxic effect of Regadenoson. Specifically, adenosine mediated effects may be enhanced. Consider therapy modification

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Riociguat: Dipyridamole may enhance the hypotensive effect of Riociguat. Avoid combination

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy


Monitoring Parameters

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])


Lab Test Interferences


Test Interactions

Concurrent caffeine or theophylline use may demonstrate a false-negative result with dipyridamole-thallium myocardial imaging.


Adverse Reactions


Oral: Frequency not always defined.

Cardiovascular: Angina pectoris, flushing

Central nervous system: Dizziness (14%), headache (2%)

Dermatologic: Skin rash (2%), pruritus

Gastrointestinal: Abdominal distress (6%), diarrhea, vomiting

Hepatic: Hepatic insufficiency

Postmarketing and/or case reports: Alopecia, arthritis, cholelithiasis, dyspepsia, fatigue, hepatitis, hypersensitivity reaction, hypotension, laryngeal edema, malaise, myalgia, nausea, palpitations, paresthesia, tachycardia, thrombocytopenia

IV:

>10%:

Cardiovascular: Exacerbation of angina pectoris (20%)

Central nervous system: Dizziness (12%), headache (12%)

1% to 10%:

Cardiovascular: ECG abnormality (5% to 8%; ST-T changes, extrasystoles), hypotension (5%), flushing (3%), tachycardia (3%), altered blood pressure (2%), hypertension (2%)

Central nervous system: Pain (3%), fatigue (1%), paresthesia (1%)

Gastrointestinal: Nausea (5%)

Respiratory: Dyspnea (3%)

<1%, postmarketing, and/or case reports (Limited to important or life-threatening): Abdominal pain, arthralgia, ataxia, back pain, bronchospasm, cardiac arrhythmia (ventricular tachycardia, bradycardia, AV block, SVT, atrial fibrillation, asystole), cardiomyopathy, cough, depersonalization, diaphoresis, dysgeusia, dyspepsia, dysphagia, ECG abnormality (unspecified), edema, eructation, flatulence, hypersensitivity reaction, hypertonia, hyperventilation, increased appetite, increased thirst, injection site reaction, leg cramps (intermittent claudication), malaise, mastalgia, muscle rigidity, myalgia, myocardial infarction, orthostatic hypotension, otalgia, palpitations, perineal pain, pharyngitis, pleuritic chest pain, pruritus, renal pain, rhinitis, skin rash, syncope, tenesmus, tinnitus, tremor, urticaria, vertigo, visual disturbance, vomiting, weakness, xerostomia


Warnings/Precautions


Disease-related concerns:

- 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 Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies.


Actions


Pharmacology

Inhibits the activity of adenosine deaminase and phosphodiesterase, which causes an accumulation of adenosine, adenine nucleotides, and cyclic AMP; these mediators then inhibit platelet aggregation and may cause vasodilation; may also stimulate release of prostacyclin or PGD2; causes coronary vasodilation


Absorption

Readily, but variable


Metabolism

Hepatic to glucuronide conjugate


Excretion

Feces (as glucuronide conjugates and unchanged drug)


Time to Peak

Serum: 2-2.5 hours


Half-Life Elimination

Terminal: 10-12 hours


Protein Binding

91% to 99%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, severe dizziness, passing out, arrhythmia, shortness of breath, or seizures (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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