Ergotamine, Dihydroergotamine: Current Uses and Problems

P. Tfelt-Hansen

Disclosures

Curr Med Res Opin. 2001;17(1s) 

In This Article

Therapeutic use of Ergotamine and Dihydroergotamine

Ergotamine is still widely used in some countries for the treatment of severe migraine attacks. It is generally regarded as a safe and useful drug when prescribed in the correct dose and in the absence of contraindications[7,18,19]. Among European headache experts, however, there is consensus that for most migraine patients requiring a specific antimigraine treatment, a triptan is generally a better option than ergotamine from both an efficacy and side-effect standpoint[8]. Headache recurrence is probably less likely with ergotamine than with triptans[8], and in patients with very long attacks (> 48 h), and patients with frequent headache recurrence, ergotamine is probably useful.

No similar consensus has been reached for dihydroergotamine which is generally held to result in fewer side-effects than ergotamine[2].

Routes of Administration and Dosages of Ergotamine
Although still used orally, ergotamine is generally better administered, provided it is acceptable to the patient, by rectal route because of improved absorption[8]. The extremely low oral and low rectal bioavailabilities of ergotamine (see above), result in marked inter-patient variability with regard to the amounts of the drug reaching the circulation. There should thus be no 'standard dose', but the dose should be tailored to the individual patient. The frequent occurrence of nausea as a side-effect (10-20% of patients) often limits the use of ergotamine. The drug has a direct effect on the chemoreceptor trigger zone in medulla[7], and patients vary considerably in their sensitivity to this effect. It is often useful to let patients try ergotamine during a headache-free interval to ensure that no nausea occurs. They should try the initial recommended dose of ergotamine (see below), e.g. 1mg rectally, and if this dose does not cause nausea it can be used in the treatment of an attack. Also, the next dose increment, if necessary, should be tested and found not to cause nausea. Ergotamine should be administered in the selected dose as soon as the patient is sure that a migraine attack is developing. The dose of ergotamine should not be divided, as is often recommended. The recommended starting dose for oral ergotamine is 2mg and the maximum dose is 6 mg. For rectal ergotamine the recommended starting dose is 1mg (half a suppository) and the recommended maximum dose is 4 mg (two suppositories).

Frequency of Dosing
A persistent (at least 24 hours) vasoconstrictor effect occurs after a single therapeutic dose of ergotamine[2,9]. Ergotamine should thus not be given daily as this will lead to chronic vasoconstriction and habituation - see later; ideally patients should not be allowed more than one dose per week or six per month[8].

Side-effects
The side-effects of ergotamine are listed in Table 2. After a single dose they include nausea and vomiting, abdominal discomfort, acroparaesthesia and leg cramps. In patients with ischaemic heart disease, ergotamine, given in therapeutic doses, has in a few cases caused variant angina, myocardial infarction and cardiac arrest[8,20]. After chronic daily intake, unwanted symptoms include those attributable to vasospasm (such as intermittent claudication) and ergotamine-induced headache.

Any medication used for the treatment of migraine attacks can probably be misused by being taken daily or almost daily. Migraine patients taking ergotamine daily suffer from several kinds of headaches: (1) a constant, diffuse, dull headache; (2) they may still experience migraine attacks; (3) if ergotamine is stopped the patient experiences a withdrawal headache resembling a severe and prolonged migraine attack. Treatment of ergotamine abuse is abrupt withdrawal. Patients often need to be hospitalized in the withdrawal phase (for details about ergotamine abuse, see reference 8). Ergotamine abuse can be prevented by limiting the frequency of dosing (see above).

Contraindications
As summarized in Table 2, ergotamine is contraindicated in cardiovascular disease, sepsis, liver and kidney disease, pregnancy (because of the prominent uterotonic action[21,22] and breast-feeding. Ergotamine should not be used concomitantly with certain drugs, including triacetyloleandomycin and erythromycin, which decrease metabolism of ergotamine.

Precautions
One-half the normally effective dose of ergotamine should be tried in patients on methysergide because of the vasoconstrictor action of methysergide[2]. Triptans have a minor peripheral vasoconstrictory effect[23] and should generally not be used together with ergotamine.

Parenteral dihydroergotamine (not available in all countries) can be used in the office and as an alternative to morphinometics in the emergency department[24]. In addition, it has been recommended for the treatment of status migrainosus[25].

Intranasal Dihydroergotamine
The recommended initial dose for intranasal dihydroergotamine is one 1mg (one puff in each nostril). If needed, the patient can repeat the dose of 1mg after 15 min. I would, however, recommend that the patient is instructed to titrate the effective dose of intranasal dihydroergotamine between 1 and 2 mg, which then should be administered as a single dose. In order to avoid drug-induced headache dihydroergotamine should not be used daily.

Side-effects
With parenteral dihydroergotamine the most common side-effect is nausea and concomitant administration of an anti-emetic is recommended for i.v. use[2]. Leg pain, paraesthesia and a few cases of angina and ergotism have been reported[2]. With intranasal dihydroergotamine the most common side-effects are transient nasal congestion, nausea, and throat discomfort[2].

Contraindications
Known hypersensitivity to ergot alkaloids, pregnancy, breast feeding, coronary arterial disease, inadequately controlled hypertension.

† With emphasis on properties relevant to the clinical use of ergot alkaloids

‡ See references 2, 7, 8, 9, 10

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