Clinically significant drug interactions with agents specific for migraine attacks

Eadie, MJ (2001) Clinically significant drug interactions with agents specific for migraine attacks. Cns Drugs, 15 2: 105-118. doi:10.2165/00023210-200115020-00003

Author Eadie, MJ
Title Clinically significant drug interactions with agents specific for migraine attacks
Journal name Cns Drugs   Check publisher's open access policy
ISSN 1172-7047
Publication date 2001
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2165/00023210-200115020-00003
Volume 15
Issue 2
Start page 105
End page 118
Total pages 14
Editor Katherine Palmer
Place of publication Auckland NZ
Publisher Adis International Ltd
Collection year 2001
Language eng
Subject CX
320503 Clinical Pharmacology and Therapeutics
730104 Nervous system and disorders
Abstract The drugs which provide specific relief from migraine attacks, the ergopeptides (ergotamine and dihydroergotamine) and the various 'triptans' (notably sumatriptan), are often prescribed for persons already taking various migraine preventative agents, and sometimes drugs for other indications. As a result, migraine-specific drugs may become involved in drug-drug interactions. The migraine-specific drugs all act as agonists at certain subclasses of serotonin (5-hydroxytryptamine; 5-MT) receptor, particularly those of the 5-HT1D subtype, and produce vasoconstriction through these receptor-mediated mechanisms. The oral bioavailabilities of these drugs, particularly those of the ergopeptides, are often incomplete, due to extensive presystemic metabolism. As a result, if migraine-specific agents are coadministered with drugs with vasoconstrictive properties, or with drugs which inhibit the metabolism of the migraine-specific agents, there is a risk of interactions occurring which produce manifestations of excessive vasoconstriction. This can also occur through pharmacodynamic mechanisms, as when ergopeptides or triptans are coadministered with methysergide or propranolol (although a pharmacokinetic element may apply in relation to the latter interaction), or if one migraine-specific agent is used shortly after another. When egopeptide metabolism is inhibited by the presence of macrolide antibacterials, particularly troleandomycin and erythromycin, the resultant interaction can produce ergotism, sometimes leading to gangrene. Similar pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably apply to combination of the ergopeptides with HIV protease inhibitors (indinavir and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise circulating triptan concentrations, although this does not yet seem to have led to reported clinical problems. Caffeine may cause increased plasma ergotamine concentrations through an as yet inadequately defined pharmacokinetic interaction. However, a direct antimigraine effect of caffeine may contribute to the claimed increased efficacy of ergotamine-caffeine combinations in relieving migraine attacks. Serotonin syndromes have been reported as probable pharmacodynamic consequences of the use of ergots or triptans in persons taking serotonin reuptake inhibitors. There have been two reports of involuntary movement disorders when sumatriptan has been used by patients already taking loxapine. Nearly all the clinically important interactions between the ergopeptide antimigraine agents and currently marketed drugs are likely to have already come to notice. In contrast, new interactions involving the triptans are likely to be recognised as additional members of this family of drugs, with their different patterns of metabolism and pharmacokinetics, are marketed.
Keyword Clinical Neurology
Pharmacology & Pharmacy
Antimigraine Compound Zolmitriptan
Macrolide Antibiotics
Serotonin Syndrome
Pharmacokinetic Interaction
Ergotamine Interaction
Cytochrome-p450 3a4
Concomitant Use
Q-Index Code CX

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 14 Aug 2007, 15:42:09 EST