Rapid development of tolerance to dipyridamole‐associated headaches

Theis, Jochen G.W.; Deichsel, Guntram; Marshall, S

doi:10.1046/j.1365-2125.1999.00072.x

Cited by 44 publications

(28 citation statements)

References 12 publications

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“…In these studies, headache was also the main reason for discontinuation of the dual therapy. Yet another study with DP found 2 out of 3 patients with headache on the first day of treatment but only 3% on the fifth day of treatment [13]. The headache peaked 2–3 h after the administration coinciding with the peak of the plasma concentrations of DP with no relation to interindividual differences due to pharmacokinetic parameters.…”

Section: Discussionmentioning

confidence: 99%

Dipyridamole-Associated Headache in Stroke Patients – Interindividual Differences?

Lökk¹

2009

Eur Neurol

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Background: Secondary pharmacological prevention of ischemic stroke or transient ischemic attack (TIA) is often provided with acetylsalicylic acid (ASA), dipyridamole (DP) or a combination of the two. A problem with DP is the occurrence of headache, sometimes leading to medication cessation. By using a titration regime of DP the incidence of headache gets lower. However, there are no studies on interindividual differences in the incidence of headache with regard to age, gender, localization of stroke and the number of days since stroke onset. Method: 20 stroke units in Sweden recruited newly diagnosed stroke and TIA patients in need for thrombocyte antiaggregating therapy. They were offered a titration regime of the combination ASA 25 mg + DP 200 mg once daily for 5 days followed by twice daily. Baseline characteristics of the patients were recorded and headache symptoms were filled in by each patient in a diary for 10 consecutive days. Rescue medication with paracetamol was optional. Results: 174 ischemic stroke patients with a mean age of 70.3 years, 63% men and 37% women, were recruited. Headache of any kind was reported in 70 patients (40.2%) and 37 (21.3%) assessed the headache as moderate/severe. Six patients stopped medication due to headache. A subsiding character of the headache was found with a mean of 3.1 days. Patients with TIA had a significantly higher risk of getting headache compared to manifest stroke, regardless of localization. There was a trend towards higher risk in younger age groups and females. No effect was seen on the number of days since stroke onset. Conclusion: DP is often associated with subsiding headache, however, with only few patients stopping medication due to headache. Being a younger female with a TIA seems to increase the risk of getting headache when having DP medication. Careful and adequate information about the possibly occurring headache should be given to patients prescribed a DP medication in order to increase compliance and optimize the pharmacological secondary stroke prevention.

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Section: Discussionmentioning

confidence: 99%

Dipyridamole-Associated Headache in Stroke Patients – Interindividual Differences?

Lökk¹

2009

Eur Neurol

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“…Possibly tolerance for this side effect builds up, but the exact mechanism is unknown [3]. The duration of headache varies from 2 to 10 days [3,4,5,9].…”

Section: Introductionmentioning

confidence: 99%

“…The duration of headache varies from 2 to 10 days [3,4,5,9]. Although the appearance of headache is not linked to the pharmacokinetic profile of the drug, it may possibly be associated with plasma peak concentrations [3]. …”

Section: Introductionmentioning

confidence: 99%

The Effect of a Slower than Standard Dose Escalation Scheme for Dipyridamole on Headaches in Secondary Prevention Therapy of Strokes: A Randomized, Open-Label Trial (DOSE)

et al. 2014

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Background: Combination therapy with acetylsalicylic acid and dipyridamole is first-line treatment in secondary prevention of strokes. Approximately 40% of patients report headache as a side effect of dipyridamole. Dose escalation of dipyridamole reduces this side effect. In practice, different dose escalation schemes are used. In theory, slower dose escalation than a standard scheme reduces headaches even more. This study aimed to find the best dose escalation scheme for prevention of headaches as a side effect of dipyridamole in the secondary prevention of strokes. Methods: In this randomized, open-label, 4-week trial, 114 patients who had an ischemic stroke or transient ischemic attack were randomized to receive either a standard or slow dose escalation scheme of dipyridamole. Participants were asked to report the four most common side effects of dipyridamole in a study diary on study days 1, 3, 5, 7, 14, 21 and 28. They were asked to score headache intensity on a visual analog scale (VAS). Participants were unaware that the trial was focused on headaches. Primary end point was to determine if a slow dose escalation scheme reduces the percentage of patients with headaches. Secondary objective was to determine the number of patients who discontinued treatment with dipyridamole because of headaches. Results: Overall 37 patients (38%) of the final population reported headache, 19 (39%) in the standard dose escalation group and 18 (37%) in the slow dose escalation group (p = 1.0). In the standard dose escalation group patients scored headaches (VAS >4) on an average of 3.3 days and patients in the slow dose escalation group on 3.6 days (p = 0.82). Mean VAS scores on study days 1, 3, 5, 7, 14 and 21 ranged from 1.4 to 3.7 in both groups. These scores did not differ significantly. However, on day 28 patients scored a significantly lower mean VAS score in the standard dose escalation group than in the slow dose escalation group (2.5 vs. 4.8; p = 0.05). In the standard dose escalation group 6 patients (11%) discontinued treatment because of side effects of dipyridamole and 3 patients (6%) in the slow dose escalation group (p = 0.49, Fisher's exact test). Conclusion: We showed that slower than standard dose escalation of dipyridamole in combination therapy with acetylsalicylic acid does not reduce headaches as a side effect. The use of such schemes should be discontinued in clinical practice. Slow dose escalation might, however, reduce the number of patients who discontinue treatment, but further research is needed to confirm this.

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“…However, a substantial number of patients complain of headache shortly after starting treatment. The nature, frequency and severity of dipyridamole-induced headache have been characterized [2]. The headache occurs shortly after the first dose, tends to occur more frequently in healthy subjects, and wanes in frequency and severity over 3–5 days in the majority of subjects.…”

Section: Introductionmentioning

confidence: 99%

Dose Titration to Reduce Dipyridamole-Related Headache

Chang¹,

Ryu²,

Lee³

2006

Cerebrovasc Dis

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Background: Combination of low-dose aspirin and modified-release dipyridamole (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over aspirin alone. However, headaches were reported in more patients receiving dipyridamole-containing agents than in those receiving placebo. We undertook a randomized, double-blind, placebo-controlled trial to evaluate which dosing regimens of ASA+MR-DP have better tolerance. Methods: This trial randomized 146 patients with a history of ischemic cerebrovascular disease into three groups: placebo (days 1–28), reduced dose (placebo on days 1–4, ASA+MR-DP once daily before bed during days 5–14, and b.i.d. on days 15–28), and regular dose (placebo on days 1–4, and ASA+MR-DP b.i.d. on days 5–28). Using Chinese diary card, headache was assessed as mean cumulated headache (Σ frequency × intensity/occurrence days × study days) over the study period, and was graded 0–4 according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version 2.0. Results: Intent-to-treat patients after randomization was 46 in placebo group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse effects, headache of any grade occurred significantly more in the regular dose group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated headache was higher (p < 0.05) in the regular dose group than in the reduced group during days 5–14. Of 27 patients who dropped out, 15 (55.6%) were due to headache, which was substantially more in regular dose (8, 53.3%), though the difference was statistically insignificant. Conclusions: Initial reduced dose treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems better tolerated by those susceptible to phosphodiesterase inhibitor-induced headache.

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Rapid development of tolerance to dipyridamole‐associated headaches

Cited by 44 publications

References 12 publications

Dipyridamole-Associated Headache in Stroke Patients – Interindividual Differences?

Dipyridamole-Associated Headache in Stroke Patients – Interindividual Differences?

The Effect of a Slower than Standard Dose Escalation Scheme for Dipyridamole on Headaches in Secondary Prevention Therapy of Strokes: A Randomized, Open-Label Trial (DOSE)

Dose Titration to Reduce Dipyridamole-Related Headache

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