Headache dipyridamole

Adverse reactions at therapeutic doses are usually minimal and transient. With long-term use, initial side effects usually disappear. The following reactions were reported in 2 heart valve replacement trials comparing dipyridamole and warfarin therapy to either warfarin alone or warfarin and placebo dizziness, abdominal distress, headache, and rash. 

A 74-year-old woman had a 3-year history of mild dysarthria, dizziness, and gait ataxia, accompanied by two transient ischemic attacks with involuntary ballistic movements of her left arm lasting several seconds each, and another transient ischemic attack with a right homonymous hemianopia lasting 30 minutes. About 45 minutes after her first-ever oral administration of dipyridamole plus aspirin she developed a transient cerebellar deficit that reproduced features of previous vertebrobasilar ischemic events, as well as severe headache, flushing, and diarrhea. 

The acute onset, the pattern of the cerebellar deficit, and the absence of features of epilepsy suggested that the episode was a transient ischemic attack. Aspirin is not known to cause transient ischemic attacks, and only rarely causes headache, flushing, and diarrhea. Since headache, flushing, and diarrhea, which can be caused by dipyridamole, occurred at the same time as the transient ischemic attacks and did not recur after withdrawal, dipjridamole may have caused the transient ischemic attacks. However, it was not clear whether the attacks occurred despite treatment rather than because of it. 

In the Second European Stroke Prevention Study, headaches associated with dipyridamole (in 8% of patients taking dipyridamole or dipyridamole + aspirin... 

The predictive factors for headaches were explored in a study of the bioequivalence of two formulations of dipyridamole 200 mg in a modified-release combination with aspirin 25 mg (17). The conclusion was that the rapid fall in the incidence of headaches over time implied that most patients quickly develop tolerance to dipjridamole-associated headaches. However, in the European Stroke Prevention Study 2, headache was the most common adverse event, and it occurred more often in dipyridamole-treated patients (18). 

Theis JG, Deichsel G, Marshall S. Rapid development of tolerance to dipyridamole-associated headaches. Br J Clin Pharmacol 1999 48(5) 750-5. 

Adverse effects with dipyridamole thallium testing are minimal, the main adverse effects being chest pain (with or without ischemic changes on the ECG), headache, dizziness, and nausea. Adverse effects are related to the increased adenosine activity and can be ameliorated by xanthine compounds because they are direct competitive antagonists of adenosine. Caffeine products must be avoided for about 24 hours prior to the test. Adenosine is associated with a higher incidence of adverse effects (80% versus 50%), but these are very transient, and some studies have shown that patients prefer it over dipyridamole. Both agents are relatively contraindicated in patients with a history of bronchospasm. 

In the ESPS-2, 25% of the patients who received combination dipyridamole and aspirin discontinued the therapy early, and the rate of discontinuation owing to headache was more than three times as common (10%) as in the aspirin-alone group (3%). Other reasons for discontinuation were GI problems. Slow initiation of ERDP -E ASA at one capsule at bedtime daily for 2 or 3 days can be tried in order to lessen headache symptoms. The headache due to ERDP + ASA is mostly self-limiting and decreases after several days. ... 

Nervous system The susceptibility factors for dip)Tidamole-induced headache have been studied in an analysis of data from the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) and the Second European Stroke Ifrevention Study (ESPS 2). In ESPRIT, dipyridamole-induced headache was significantly associated with female sex, absence of hypertension, and nonsmoking, and in ESPS 2 with female sex and absence of ischemic lesions on imaging [143 ]. 

Lokk J. Dipyridamole-associated headache in stroke patients—interindividual differences Eur Neurol 2009 62(2) 109-13. 

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