Pharmacy & Therapeutics- July 2008 - (Page 409) CONTINUING EDUCATION CREDIT Triptans: 5-Hydroxytriptamine (Serotonin Receptor Agonists) The triptans have emerged as drugs of choice in the abortive management of migraine, especially in patients who have not responded to or who cannot tolerate simple analgesics or NSAIDs.35,36,91 With seven agents on the market (Table 2), they are available in various dosage forms that offer numerous delivery options.148–154 The mechanism of action of the triptans, although similar to that of ergots, has a more selective serotonin agonist receptor profile, acting on 5-HT1b,1d receptors and lacking interactions with adrenergic and dopaminergic receptors. Actions at these receptors result in their proposed migraine mechanism, including vasoconstriction of intracranial blood vessels; inhibition of vasoactive neuropeptide release; blocking transmission of pain signals; and influencing the plasma vasodilation, extravasation, and inflammation that occur in migraine.155–162 The pharmacokinetic properties of the triptans include differences in their bioavailability, onset of action, metabolism pathways, half-lives, and mode of excretion (see Table 2). Bioavailability ranges from 15% with sumatriptan to 70% with naratriptan (Amerge, GlaxoSmithKline), even though these differences do not appear to correlate with clinical Table 2 Serotonin Receptor Agonists (Triptans) Drug Sumatriptan (Imitrex) Cost considerations with the SQ form Formulation/Dosage • SQ 6 mg; may repeat in 1 hour, max. 12 mg q 24 hours (autoinjector) • Intranasal 5–20 mg, 1 spray in 1 nostril per dose; may repeat MR in 2 hours, max. 40 mg/day • Oral 25–50 mg; may repeat q 2 hours, max. 200–300 mg/24 hours • Oral 5–10 mg; may repeat in in 2 hours, max. 20–30 mg daily, 15 mg if taking propranolol; MLT product dissolves on tongue; no need for water • Oral 2.5–5 mg; may repeat in 1–2 hours, max. 10 mg daily; ZMT product dissolves on tongue; no need for water • Intranasal 5 mg; may repeat q 2 hours, max. 10 mg • Oral 1–2.5 mg; may repeat in 4 hours, max. 5 mg daily Pharmacokinetics • SQ onset: 10–15 minutes Bioavailability: 97% • Intranasal onset: 15–20 minutes Bioavailability: 17% • Oral onset: 0.5 to 1.5 hours High first-pass metabolism Bioavailability: oral 15% Half-life (all dosage forms): about 2 hours Onset: 30–120 minutes Half-life 2–3 hours Bioavailability: 45% MLT: perceived as faster onset Onset: 45 minutes to 1 hour Half-life: 3 hours Bioavailability: 40% ZMT: perceived as faster onset Intranasal onset: 15–20 minutes Onset: 1–3 hours Half-life: 6 hours Bioavailability: 60%–70% Onset: 30 minutes – 2 hours Half-life: 3–4 hours Bioavailability: 70% Onset: 2–4 hours Half-life: 26 hours Bioavailability: about 30% Onset: 1–2 hours Half-life: 4–6 hours Bioavailability: 50% Comment* Metabolism (MAO-A) • Fast onset, especially SQ • A new combination product with naproxen (Treximet) is now available. Rizatriptan (Maxalt) Maxalt-MLT (dissolving form) Metabolism (MAO-A) • Fast onset Zolmitriptan (Zomig) Zomig-ZMT (dissolving form) Metabolism (CYP 450, 1A2 MAO-A), active metabolite • Two to six times more potent vs. parent drug • Fast onset Metabolism (CYP 450) • 50% excreted unchanged by kidneys • Slow onset, long duration Metabolism (CYP 450, 3A4, 2D6 MAO-A) • 40% excreted unchanged by kidneys Metabolism (CYP 1A2) • Slow onset, longer duration Metabolism (CYP 450, 3A4) • Fast onset Naratriptan (Amerge) Almotriptan (Axert) • Oral 6.25–12.5 mg; may repeat in 2 hours, max. 25 mg daily • Oral 2.5 mg; may repeat in 2 hours, max. 7.5 mg daily • Oral 20–40 mg; may repeat one time, max. 80 mg daily Frovatriptan (Frova) Eletriptan (Relpax) CYP = cytochrome; MAO = monoamine oxidase; max. = maximum; SQ = subcutaneous. * Monitor usage and side effects of all agents. Adapted from references 121, 148–154, 159, 164, and 169. Vol. 33 No. 7 • July 2008 • P&T® 409
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