DRUG INTERACTIONS

Almotriptan has a lower incidence of drug interactions than the other trip-tans. Approximately 12% of the drug is metabolized by the CYP450-3A isoenzyme, with alternative pathways, including monoamine oxidase (MAO-A) oxidative deamination. Almotriptan’s plasma concentrations were shown to increase by 37% when coadministered with the monoamine oxidase inhibitor moclobemide. However, dosage adjustments are not warranted with this combination. Naratriptan (Amerge, GlaxoWellcome) is the only other triptan not con-traindicated with the MAO-inhibitors.

Coadministration of almotriptan with drugs such as propranolol, vera-pamil and selective serotonin reup-take inhibitors (SSRIs) showed no significant differences in plasma concentrations. However, patients taking any of the SSRIs (i.e., fluoxetine generic, or sertraline canadian), should be counseled on the potential risk of d syndrome (i.e., weakness, hyperreflexia, incoordination). In addition, almotriptan should not be taken within 24 hours of any other 5HT1B/1D agonist because of this potential syndrome. Coadminis-tra-tion of ketoconazole resulted in a 60% increase in almotriptan plasma concentrations and therefore the use of the two medications should be avoided. Other potent CYP 3A4 inhibitors (i.e., canadian erythromycin) should be used with caution in patients taking almotriptan or any of the 5-HT1B/1D agonists.

Table 2 Summary of Contraindications and Warnings

Patients with uncontrolled hypertensionPatients with ischemic heart disease (angina pectoris, history of myocardial infarction or documented silent ischemia)

Patients with coronary artery vasospasm (Prinzmetal’s angina)

Not to be administered within 24 hours of another 5-HT|g/|D agonist or ergotamine-containing or ergotamine-like medication (i.e., dihydroergotamine, methysergide)

Patients diagnosed with hemiplegic or basilar migraine

The constrictive effects of the triptans are predominately on the meningeal vessels; however, there is still concern with coronary vaso-constriction, although to a lesser extent. Therefore, almotriptan as well as the other agents in its class, should not be given to patients with various forms of cardiovascular disease (Table 2). Patients taking almotriptan on a long-term basis who have documented cardiovascular disease (i.e., myocardial infarction or angina) or risk factors for coronary artery disease (i.e., hypertension, diabetes, obesity, dyslipidemia) should have their cardiovascular status monitored regularly and closely.
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Well-controlled studies of almotrip-tan with pregnant women are not available, therefore it should be used only when the potential benefits outweigh the potential risks to the fetus.

PHARMACOKINETICS

Bioavailability

Although all of the triptans possess the same pharmacological actions, each has slightly different pharma-cokinetic characteristics, resulting in differences in onset and duration of action. This variation allows the prescriber to choose the most appropriate drug to optimize a patient’s therapy (Table 3). Compared to the other triptans, almotriptan has the highest oral bioavailability with a comparable onset and duration of action.

Table 3 Pharmacokinetic Parameters of the 5-HT|B/|D Agonists

5-ht|b/|d Agonist Onset of Action Tmax (hrs) TI/2 (hrs) Bioavailability (%)
Almotriptan 30 min-2 hrs 1.4-3 3 70-80
Frovatriptan 2-3 hrs 2-4 26 20-30
Sumatriptan canadian (oral) 30 min-| hr 2-2.5 2 14
Naratriptan |-3 hrs 3-4 6 63(men); 74 (women)
  30 min-2 hrs 1-1.5 2-3 45
Zolmitriptan 45 min 2 3 40-48

Side Effects

There are limited studies comparing almotriptan to the newer trip-tans. Many of the head-to-head trials use sumatriptan as the standard comparison drug. Overall, fewer side effects have been reported in patients taking almotriptan than sumatriptan (GlaxoSmith-Kline). Spierings and colleagues evaluated almotriptan compared to oral sumatriptan in the abortive treatment of migraine. The authors observed a significant difference between the reported adverse effects, specifically chest pain, of the two groups in favor of the almotrip-tan-treated group (0.3 vs. 2.2; P=0.004). Other treatment-related adverse events (i.e., diarrhea, nausea, dizziness, and somnolence) occurred one-third less often in the almotriptan-treated group than in patients receiving (P=0.001). There were no significant differences between the two groups with respect to cardiovascular adverse events (i.e., palpitations, syncope, tachycardia, and abnormal cardiac rhythm) (P=0.06).