Zolmitriptan pharmacokinetics

Nasal spray - Administer 1 dose of 5 mg for the treatment of acute migraine. If the headache returns, the dose may be repeated after 2 hours. Do not exceed a maximum daily dose of 10 mg in any 24-hour period. Individuals may vary in response to zolmitriptan. The pharmacokinetics of a 5 mg nasal spray dose is similar to the 5 mg oral formulations. Doses lower than 5 mg can only be achieved through the use of an oral formulation. Therefore, choose the dose and route of administration on an individual basis. The efficacy of a second dose has not been established in placebo-controlled trials. 

Some of the triptans are metabolized by monoamine oxidase and they should not be used with monoamine oxidase inhibitors. This includes almotriptan (34), rizatriptan (35), sumatriptan (36), and zolmitriptan (28). The effect of moclobemide on the pharmacokinetics of almotriptan was less than with other triptans (34). 

CYP1A2 and may therefore be expeeted to have additional interaetions. The picture with zolmitriptan beeomes more eomplieated sinee it is also metabolised by monoamine oxidase A. Naratriptan appears unlikely to undergo significant pharmacokinetic interactions since half the dose is excreted unchanged and the rest metabolised by a variety of isoenzymes. A summary of the metabolic pathways of the triptans can be found in Table 16.2 , (below). 

Selegiline on the other hand had no effect on the pharmacokinetics of zolmitriptan or its metabolites, apart from a small (7%) reduction in its renal clearance. This finding was expected, since selegiline is specific for monoamine oxidase B (but note that this specificity is lost at higher doses). No special precautions would therefore seem to be necessary if selegiline is given with sumatriptan. 

Pizotifen did not alter the pharmacokinetics or pharmacodynamics of sumatriptan or zolmitriptan, and did not alter the efficacy of acute sumatriptan for migraine. It seems unlikely that any of the other triptans will interact. 

A two-period crossover, double-blind study in 20 subjects given fluoxetine 20 mg or a placebo daily for 28 days, with zolmitriptan 10 mg on day 28, found that the pharmacokinetics of zolmitriptan were unaffected by fluoxetine. Only very slight changes were seen in the pharmacokinetics of its active metabolite. Sertraline, paroxetine, and citalopram are also not expected to alter the pharmacokinetics of zolmitriptan. However, fluvoxamine, a CYP1A2 inhibitor, is predicted to increase levels of zolmitriptan, based on the known interaction with cimetidine (see Triptans Zolmitriptan + Cimetidine , p.608). 

In a randomised, crossover study, 15 healthy subjects were given single 10-mg doses of zolmitriptan alone or with metoclopramide 10 mg. Metoclopramide had no effect on the pharmacokinetics of zolmitriptan, so there would appear to be no reason for avoiding concurrent use of these two drugs. ... 

Oral contraceptives appear to modestly raise the levels of frov-atriptan, naratriptan and zolmitriptan, and slightly increase those of sumatriptan. These changes are not considered clinically significant HRT did not appear to affect the pharmacokinetics of naratriptan. 

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