Rizatriptan pharmacokinetics

Drugs used in the treatment of acute migraine, such as sumatriptan and rizatriptan, are 5-HTiB/iD-receptor agonists and could theoretically interact pharmacodynami-cally with SSRIs to cause serotonin toxicity. Triptans are metabolized mainly by monoamine oxidase, which makes pharmacokinetic interactions with SSRIs unlikely. Although case series have suggested that sumatriptan can be safely combined with SSRIs (SEDA-22, 14), there are occasional reports of toxicity. 

Treatment of 12 healthy volunteers with paroxetine (20 mg/day for 14 days) did not alter the pharmacokinetics or pharmacodynamic effects of an acute dose of rizatriptan (10 mg orally) (29). These data are reassuring, but (as with sumatriptan) it is possible that sporadic cases of 5-HT neurotoxicity could still occur when rizatriptan is combined with an SSRI. 

Goldberg MR, Lowry RC, Musson DG, Birk KL, Fisher A, De Puy ME, Shadle CR. Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine. J Clin Pharmacol 1999 39(2) 192-9. 

Van Haarst AD, Van Gerven JM, Cohen AF, De Smet M, Sterrett A, Birk KL, Fisher AL, De Puy ME, Goldberg MR, Musson DG. The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers. Br J Clin Pharmacol 1999 48(2) 190-6. 

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). 

Goldberg MR, Sciberras D, De Smet M, Lowry R, Tomasko L, Lee Y, Olah TV, Zhao J, Vyas KP, Halpin R, Kari PH, James I. Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HTib id agonist differential effects of propranolol, nadolol and metoprolol. Br J Qin Pharmacol 2001 52(l) 69-76. 

Barrish, A. et al.. The use of stable isotope labehng and liquid chromatography/tandem mass spectrometry techniques to study the pharmacokinetics and bioavadability of the antimigraine drug, MK-0462 (rizatriptan) in dogs. Rapid Commun. Mass Spectrum., 10 1033-1037, 1996. 

A placebo-controlled study in 20 healthy young women taking a combined oral eontraceptive (ethinylestradiol/norethisterone 35 micrograms/1 mg) found that the concurrent use of rizatriptan (6 days of 10 mg daily followed by 2 days of 10 mg every 4 hours to a total of 3 doses daily) did not affect the pharmacokinetics of either contraceptive steroid. Blood pressure, heart rate and temperature were unaffected and adverse effects were similar to those seen with placebo. ... 

Although data are limited, the minor to modest possible ineieases in frov-atriptan, naratriptan, sumatriptan and zoimitriptan pharmacokinetics described are not likely to produce clinically relevant adverse effects. Almotriptan, rizatriptan and sumatriptan do not appear to have any clinically important effect on levels of contraceptive steroids. The significance of the single case report of ischaemic colitis associated with concurrent use of naratriptan and a combined oral contraceptive is unclear. Note that ischaemic colitis has, rarely, been reported with naratriptan itself The manufacturers have found no cases of ischaemic colitis in approximately 450 women on oral contraceptives and taking naratriptan for prophylaxis for 5 to 6 days. However, caution may be needed with concurrent use in those patients with risk factors for ischaemic colitis, such as those with a history of abdominal surgery, low blood pressure, diabetes, cardiovascular disease or stroke. 

Shadle CR, Liu G, Goldberg MR. A double-blind, pl ebo-controlled evaluation of the effect of oral doses of rizatriptan 10 mg on oral contraceptive pharmacokinetics in healthy female vohmteers. J Clin Pharmacol (2000) 40, 309-15. 

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