Ergot derivatives (various preparations)
Ergot derivatives (active ingredients: dihydroergocristin, dihydroergotamine, dihydroergotoxin, nicergoline, dihydroergocryptin) are approved in various European member states under different names. The indications include cardiovascular diseases, such as hypotension and circulatory problems, as well as neurological indications, such as dementia, Alzheimer's disease and migraine.
The Committee for Human Medicinal Products (CHMP) of the European Medicines Agency (EMA) recommended restricting the indication for these preparations.
Measures at EU level
Under an Article 31 procedure, the CHMP evaluated all available data in this regard, including clinical studies, data from the spontaneous reporting system, and published information. The main risks associated with the use of ergot derivatives were found to be the occurrence of fibrosis and ergotism.
Among these, fibrosis (including retroperitoneal, cardiac, pulmonary, and pleural forms) was most frequently reported in association with dihydroergotamine. However, because of their common mechanism of action, all members of this drug class have the potential to induce fibrosis, particularly of the heart valves. Any differences in the observed frequency can be explained by differences in binding capacity for serotonin receptors, but also by the difficulties of diagnosing fibrosis and the associated reduced frequency of reporting.
Furthermore, there is a risk for the occurrence of ergotisms, which in some observed cases could be classified as severe and potentially fatal. The affected patients were of younger age (mean 41 years), and the time from initiation of therapy to onset was less than two months (mean two days).
In comparison, the available data to demonstrate efficacy in some of the indications were limited. The CHMP therefore decided to restrict the indications accordingly (see recommendations for users below). The final decision of the European Commission is expected in the coming weeks.
Situation in Austria
In Austria, the following proprietary medicinal products are approved:
- DHE "ratiopharm" 2.5 mg capsules
- DHE "ratiopharm 5 mg capsules
- Dihydergot 2.5 mg tablets
- Ergomed drops
- Ergotop 20 mg film-coated tablets
- Ergotop 30 mg film-coated tablets
- Ergovasan 2 mg/ml drops
- Ergovasan 2.5 mg retard Capsules
- Ergovasan 5 mg retard Capsules
- Hydergin Fas 4.5 mg film-coated tablets
- Hydergin 1 mg/ml drops
- Hydergin 1 mg tablets
- Hydergin 2 mg tablets
- Hydergin SRO 6 mg capsules
- Migranal 4 mg/ml nasal spray
- Nicergin film-coated tablets
- Sermion 30 mg film-coated tablets
BASG has received a total of eight case reports for these preparations.
BASG recommendations for users:
Preparations containing the active ingredients dihydroergocristin, dihydroergotamine, dihydroergotoxin, nicergoline or the combination of dihydroergocryptin with caffeine should no longer be prescribed in the following indications:
- Symptomatic therapy of chronic pathological cognitive and neurosensory impairment in old age (excluding Alzheimer's disease or dementia!).
- Additional therapy of intermittent claudication in symptomatic peripheral occlusive disease (PAVK, stage II)
- Additional therapy for Raynaud's syndrome
- Additional therapy for visual acuity reduction and visual field defects with presumed vascular cause
- Acute retinopathy of vascular cause
- Migraine prophylaxis
- Orthostatic hypotension
- Symptomatic therapy of veno-lymphatic insufficiency
Therapeutic alternatives should be sought for patients currently being treated with the above agents for these indications Other approved indications other than those listed above remain in effect
BASG recommendations for patients:
- The use of medicines containing ergot derivatives is no longer recommended in some of the previous indications (such as circulatory problems or some neurological conditions) because the benefit of their use no longer outweighs the associated risk.
- If you are taking a preparation containing any of the active ingredients dihydroergocristin, dihydroergotamine, dihydroergotoxin, nicergoline, or the combination of dihydroergocryptin with caffeine, please contact your treating physician to determine if a change in therapy is necessary.
Further information:European Medicines Agency press release, June 28, 2013.