Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig™, 311C90)

Abstract

Seven randomized studies in healthy volunteers have investigated interactions between zolmitriptan (Zomig, formerly 311C90), a 5HT1B/1D agonist for acute migraine therapy, and selected drugs with which there was a possibility of interaction or a likelihood of concurrent use. Co-administration of oral dihydroergotamine, ergotamine, pizotifen, fluoxetine, paracetamol (acetaminophen)/metoclopramide or selegiline had no clinically significant effects on the pharmacokinetics of zolmitriptan or its metabolites, although small changes were observed in some cases. Co-administration of propranolol resulted in a 56% increase in the area under the plasma concentration-time curve (AUC) of zolmitriptan and a 11% decrease in the AUC of the active metabolite 183C91. However, these pharmacokinetic changes are unlikely to be relevant at lower clinical doses. Moclobemide, a monoamine oxidase A (MAO-A) inhibitor, decreased the clearance of zolmitriptan and, in particular, 183C91. This suggests that MAO-A is involved in the metabolism of 183C91 and it may be prudent to limit the daily zolmitriptan dose in migraine patients maintained on a MAO-A inhibitor. The clinically insignificant blood pressure increases produced by zolmitriptan, and the tolerability profile of this agent, were unaffected by any of the concomitant medications. Clinically significant interactions between zolmitriptan and commonly co-prescribed antimigraine therapies are unlikely.

A Review of the Pharmacokinetics, Pharmacodynamics and Efficacy of Zolmitriptan in the Acute Abortive Treatment of Migraine

“…56 No clinically signifi cant interactions with other commonly prescribed medications in headache management such as metoclopramide, dihydroergotamine, fl uoxetine, and propranolol, or monoamine oxidase-B inhibitors such as selegiline, have been demonstrated. 56,57 However, it is contraindicated to give zolmitriptan to a patient on MAO-A inhibitor or within 24 hours of use of an ergot or another triptan. 59,60 In addition, it has been demonstrated that cimetidine inhibits the metabolism of zolmitriptan and its active metabolite, increasing the mean Cmax by 16 and 50% and the mean AUC by 48 and 105%, respectively.…”

The pharmacokinetics of the antimigraine compound zolmitriptan in Japanese and Caucasian subjects

“…183C91 has plasma concentrations on average around one-half to two-thirds of those of the parent compound [2]. Cytochrome P 450 (CYP) 1A2 is responsible for the biotransformation of zolmitriptan to 183C91 [3], which in turn is further metabolised to the inactive indole acetic acid metabolite by monoamine oxidase type A [4].…”

Clinical considerations preliminary to application of the Italian Society for the Study of Headache's guidelines regarding migraine prophylactic treatment

“…However, the main reported interaction between drugs assumed for symptomatic treatment and prophylactic drugs is that between propranolol and zolmitritpan. The drug-drug interaction is, however, not clinically significant when patients use a dose of 2.5 mg, as usually done in Italy [29]. From a pharmacodynamic point of view, the co-assumption of a triptan and a serotoninergic drug, like most antidepressant drugs used in headache prophylaxis, increases the risk of developing a serotoninergic syndrome [30].…”