Adenosine + Dipyridamole - Drug Interactions

Dipyridamole reduces bolus dose of adenosine necessary toconvert supraventricular tachycardia to sinus rhythm by aboutfourfold

Adenosine by rapid intravenous bolus (10 to 200 micrograms/kg in stepwise doses) was found to restore sinus rhythm in 10 of 14 episodes of tachycardia in 7 patients with supraventricular tachycardia (SVT). The mean dose was 8.8mg compared with only 1mg in two patients also taking oral dipyridamole (See reference number 1). Another study in 6 patients found that dipyridamole (560 microgram/kg intravenous bolus, followed by a continuous infusion of 5 micrograms/kg/minute) reduced minimum effective bolus dose of intravenous adenosine required to stop SVT from 68 to 17 micrograms/kg in 5 patients. In other patient, dipyridamole alone stopped SVT (See reference number 2).

Other studies in healthy subjects have clearly shown that dipyridamole reduces dose of adenosine required to produce an equivalent cardiovascular effect by fourfold(See reference number 3) or six- to sixteenfold (See reference number 4). A brief report describes a woman with paroxysmal SVT who lost ventricular activity for 18 seconds when given adenosine 6mg intravenously. She was also taking dipyridamole [dose unstated], which was considered to have contributed to loss of ventricular function (See reference number 5). Another report describes 3 of 4 patients who had heart block of 3,9 and 21-second duration respectively when given adenosine 3 to 6mg by central venous bolus. The patient with most profound heart block was also being treated with dipyridamole, which was thought to have contributed to reaction (See reference number 6).

A 79-year-old woman taking a combination of low-dose aspirin and extended-release dipyridamole (Aggrenox) became profoundly bradycardic (36 bpm), dizzy and almost fainted 2 minutes after start of an adenosine infusion for radionuclide myocardial imaging. Adenosine was stopped,and she recovered within 2 minutes. The last dose of Aggrenox had been taken 12 hrs previously (See reference number 7). However,note that bradycardia is a known adverse effect of adenosine (See reference number 8,9).

Part of explanation is that dipyridamole increases plasma levels of endogenous adenosine by inhibiting its uptake into cells

Patients will need much less adenosine to treat arrhythmias while taking dipyridamole. It has been suggested that initial dose of adenosine should be reduced by twofold(See reference number 5) or fourfold (See reference number 2). The UK manufacturers actually advise avoidance of adenosine in patients taking dipyridamole. If it must be used for supraventricular tachycardia in a patient taking dipyridamole, they recommend that adenosine dose should be reduced about fourfold (See reference number 8).

The UK manufacturers advise avoidance of adenosine in patients taking dipyridamole. If adenosine is considered necessary for myocardial imaging in a patient taking dipyridamole, they suggest that dipyridamole should be stopped 24 hrs before, or dose of adenosine should be greatly reduced (See reference number 9). This may be insufficient for extended-release dipyridamole preparations: authors of above report recommend several days (See reference number 7). Xanthines,such as intravenous aminophylline, have been used to terminate persistent adverse effects of adenosine infusion given for myocardial imaging (See reference number 9). Consider also Adenosine + Xanthines interaction,below.

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