Published: March 2002
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Cerebrovascular Events with Sumatriptan

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Prescriber Update 23(1): 8-9
March 2002

Dr David Coulter, Director, Centre for Adverse Reactions Monitoring, Dunedin

Sumatriptan (Imigran™) was monitored in the Intensive Medicines Monitoring Programme for eight years in a cohort of almost 15,000 patients.  A number of cerebrovascular events were identified at a rate of 1 per 1,000 patients.  The nature of these events highlights the importance of accurate diagnosis in patients with first presentation of migraine in middle age or later, as well as observing age and dose restrictions.  Sumatriptan is contraindicated in patients with a history of transient ischaemic attacks or stroke.

Most cerebrovascular events identified for sumatriptan are potentially preventable

Sumatriptan succinate (Imigran™) is used for the acute treatment of migraine1,2 and cluster headache.1  It is administered either subcutaneously or orally at the onset of symptoms, and appears to act mainly by constricting the cranial blood vessels.1,2  From 1991 to 1999, adverse events associated with the use of sumatriptan were monitored in the Intensive Medicines Monitoring Programme (IMMP) in a cohort of 14,964 patients.

A total of 2,344 reports were received, describing 3,978 adverse events.  A review of these data identified a small but significant number of cerebrovascular events, at a rate of 1 per 1,000 patients.  There were 15 reports of cerebrovascular events; 13 patients were using the subcutaneous preparation and two taking sumatriptan orally.  There was one fatal outcome and other events ranged from severe stroke with permanent disability to temporary dysphasia.  Several of these events occurred in patients with known risk factors and therefore were potentially preventable.

Before prescribing sumatriptan, consider differential diagnosis, age and pre-existing conditions

Incorrect diagnosis

In two patients, conditions other than migraine were causing the headaches, namely parasagittal meningioma and subarachnoid haemorrhage.  They were aged 46 and 78 years, respectively.  In both, migraine appeared to be a new diagnosis and sumatriptan was administered for the first time.  This highlights the need for a careful differential diagnosis in patients presenting with apparent migraine for the first time in middle age or later.


Two patients were aged 78 and 85.  The data sheet states that 'the use of sumatriptan in patients over 65 years is not recommended'.1,2  However when the condition is disabling, it may be reasonable to decide to use sumatriptan above the recommended age after careful risk-benefit assessment and with informed consent of the patient.

History of cerebrovascular disorder

Two patients who experienced cerebrovascular events had a history of transient ischaemic attacks (TIAs).  Sumatriptan is contraindicated in patients with a history of stroke or TIA.1,2

Maximum recommended dose of sumatriptan should not be exceeded

One patient, who had used subcutaneous sumatriptan for a number of years, suffered a pontine infarct one week after using five doses in four days.  After exhaustive investigation, no cause was found, nor were there any risk factors for cerebrovascular disease.  A causal association seems unlikely in view of a two-hour plasma half-life for the subcutaneous route.  However, the possibility has been raised that multiple doses may cause prolonged binding to cerebral vascular receptors.3  This patient used sumatriptan within the recommended guidelines, but an IMMP report has also been received of spasm causing occlusion in a peripheral artery after the recommended dose was exceeded.  The maximum dose of sumatriptan in 24 hours is 12mg subcutaneously or 300mg orally.1,2

It is important to observe contraindications and precautions

Some of these cerebrovascular events might have been hemiplegic or aphasic migraine.  However, the majority of patients were known to have had a long history of migraine without hemiplegia or aphasia occurring.  In addition, the cerebrovascular events developed only after the use of sumatriptan, making hemiplegic or aphasic migraine unlikely diagnoses.  When the contraindications and precautions for dose, age and pre-existing conditions are observed, sumatriptan is unlikely to increase the risk of cerebrovascular events.

Competing interests (author): A grant to assist monitoring was received from GlaxoWellcome in 1998.

Correspondence to Dr David Coulter, CARM, PO Box 913, Dunedin. E-mail:

  1. GlaxoSmithKline. Imigran Injection data sheet 16 July 2001.
  2. GlaxoSmithKline. Imigran Tablets data sheet 16 July 2001.
  3. Luman W, Gray RS. Adverse reactions associated with sumatriptan [letter]. Lancet 1993;341:1091-1092.


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