QT time prolongation
Adverse drug events
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Almotriptan is used to treat migraine headaches with or without aura. It is taken orally as a tablet. Almotriptan is a representative of the second generation of triptans. They have an agonistic (reinforcing) effect on the serotonin 5HT-1B and -1D receptors. The reduction in migraine headaches is explained by the narrowing of cerebral blood vessels and reduced pain transmission in the brain. In addition, the production of inflammatory substances is reduced. Almotriptan has a short half-life of 3-4 hours and has the highest bioavailability among the triptans. Like all triptans, it cannot be used preventively. Almotriptan is very well tolerated.
Since only almotriptan was entered without any further substances, no pharmacokinetic interactions can be detected.
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
Almotriptan has a mean oral bioavailability [ F ] of 70%, which is why the maximum plasma levels [Cmax] tend to change with an interaction. The terminal half-life [ t12 ] is rather short at 3.5 hours and constant plasma levels [ Css ] are reached quickly. The protein binding [ Pb ] is rather weak at 35% and the volume of distribution [ Vd ] is very large at 195 liters. Since the substance has a low hepatic extraction rate of 0.14, displacement from protein binding [Pb] in the context of an interaction can increase exposure. About 50.0% of an administered dose is excreted unchanged via the kidneys and this proportion is seldom changed by interactions. The metabolism takes place via CYP2D6 and CYP3A4, among others.
|Serotonergic Effects a||1||+|
Recommendation: As a precautionary measure, symptoms of serotonergic overstimulation should be taken into account, especially after increasing the dose and at doses in the upper therapeutic range.
Rating: Almotriptan has a mild effect on the serotonergic system. The risk of a serotonergic syndrome can be classified as low with this medication if the dosage is in the usual range.
Rating: According to our findings, almotriptan does not increase anticholinergic activity.
QT time prolongation
We do not know of any QT-prolonging potential for almotriptan.
General adverse effects
|Side effects||∑ frequency||alm|
|Chest pain||0.0 %||0.1|
|Coronary artery spasm||0.0 %||0.0|
Based on your
Abstract: This study was designed to assess the pharmacokinetics of almotriptan, a 5HT1B/1D agonist used to treat migraine attacks, when administered in the presence and absence of fluoxetine. Healthy male (n = 3) and female (n = 11) volunteers received (1) 60 mg fluoxetine daily for 8 days and 12.5 mg almotriptan on Day 8 and (2) 12.5 mg almotriptan on Day 8, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by HPLC methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance. Mean almotriptan Cmax was significantly higher following combination treatment with fluoxetine (52.5 +/- 11.9 ng/ml vs. 44.3 +/- 10.9 ng/ml, p = 0.023). Mean AUC0-infinity was not significantly affected by fluoxetine coadministration (353 +/- 55.7 ng.h/ml vs. 333 +/- 33.6 ng.h/ml, p = 0.059). Confidence interval analysis (90%) of log-transformed pharmacokinetic parameters showed that the confidence interval for AUC0-infinity was within the 80% to 125% limit for equivalence, but Cmax was not (90% CI 106%-134% of the reference mean). Adverse events were mild to moderate in intensity, and no clinically significant treatment effects on vital signs or ECGs were observed. The results show that fluoxetine has only a modest effect on almotriptan Cmax. Concomitant administration of the two drugs is well tolerated, and no adjustment of the almotriptan dose is warranted.
Abstract: AIMS: To assess the effect of a reversible MAO-A inhibitor, moclobemide, on the single-dose pharmacokinetics of almotriptan and assess the clinical consequences of any interaction. METHODS: Twelve healthy volunteers received the following treatments in a randomized, open-label, two-way crossover design (with a 1 week washout between treatments): (A) one 150 mg moclobemide tablet every 12 h for 8 days and one 12.5 mg almotriptan tablet on the morning of day 8; and (B) one 12.5 mg almotriptan tablet on day 8. Plasma almotriptan was quantified by h.p.l.c.-MS-MS, while urinary concentrations were measured by h.p.l.c.-u.v. Vital signs, ECGs, and adverse events were evaluated after almotriptan administration. Treatment effects on pharmacokinetics and vital signs were assessed by analysis of variance. RESULTS: Mean almotriptan AUC was higher (483 +/- 99.9 vs 352 +/- 75.4 ng ml-1 h, P = 0.0001) and oral clearance was lower (26.6 +/- 4.00 vs 36.6 +/- 5.89 l h-1, P = 0.0001) when almotriptan was administered with moclobemide. Mean half-life was longer (4.22 +/- 0.78 vs 3.41 +/- 0.45 h, P = 0.0002) after coadministration with moclobemide. Renal clearance of almotriptan was unaffected by moclobemide. No serious adverse events occurred and no clinically significant vital sign changes were observed. CONCLUSIONS: Moclobemide increased plasma concentrations of almotriptan on average by 37%, but the combined administration of these two compounds was well tolerated. The degree of interaction was much less than that seen previously for sumatriptan or zolmitriptan given with moclobemide.
Abstract: The interaction between almotriptan, a 5-HT1B/1D agonist, and the potent CYP3A4 inhibitor ketoconazole was examined in 16 healthy volunteers. Subjects received (A) 12.5 mg almotriptan orally on Day 2 of a 3-day regimen of 400 mg ketoconazole once daily and (B) 12.5 mg almotriptan in a crossover design. Plasma and urine concentrations of almotriptan were measured by HPLC. Treatment effects on almotriptan pharmacokinetics were assessed by analysis of variance. Ketoconazole coadministration increased mean almotriptan AUC and Cmax from 312 to 490 ng h/mL and 52.6 to 84.5 ng/mL, respectively. Mean oral clearance was decreased from 40.7 to 26.2 L/h by ketoconazole, with an accompanying increase in the fraction of almotriptan excreted unchanged in the urine (40.6% to 53.3%) and a decrease in renal clearance (16.4 to 13.8 L/h). These effects were statistically significant. The effects of ketoconazole on almotriptan clearance were consistent with inhibition of the CYP3A4-mediated metabolism and a slight effect on the active tubular secretion of almotriptan.
Abstract: The pharmacokinetics of almotriptan are linear over a range of oral doses up to 200mg in healthy volunteers. The compound has a half-life of approximately 3 hours. Almotriptan is well absorbed after oral administration and the mean absolute bioavailability is 69.1%. Maximal plasma concentrations are achieved between 1.5 and 4 hours after dose administration; however, within 1 hour after administration, plasma concentrations are approximately 68% of the value at 3 hours after administration. Food does not significantly affect almotriptan absorption. Almotriptan is not highly protein bound and is extensively distributed in the body. Approximately 50% of an almotriptan dose is excreted unchanged in the urine; this is the predominant single mechanism of elimination. Renal clearance is mediated, in part, through active tubular secretion, while the balance of the almotriptan dose is metabolised to inactive compounds. The predominant route of metabolism is via monoamine oxidase-A, and cytochrome P450 (CYP) mediated oxidation (via CYP3A4 and CYP2D6) occurs to a minor extent. Almotriptan clearance is moderately reduced in elderly subjects, but the magnitude of this effect does not warrant a dose reduction. Sex has no significant effect on almotriptan pharmacokinetics. Almotriptan pharmacokinetic parameters do not differ between adolescents and adults, and absorption is not affected during a migraine attack. As expected, renal dysfunction results in reduced clearance of almotriptan. Patients with moderate-to-severe renal dysfunction should use the lowest dose of almotriptan and the total daily dose should not exceed 12.5 mg. Similar dosage recommendations are valid for patients with hepatic impairment, based on the clearance mechanisms for almotriptan. Drug-drug interaction studies were conducted between almotriptan and the following compounds: fluoxetine, moclobemide, propranolol, verapamil and ketoconazole. No significant pharmacokinetic or pharmacodynamic interactions with almotriptan were observed for fluoxetine or propranolol. Almotriptan clearance was reduced, to a modest degree, by moclobemide and verapamil, which was consistent with the contribution of monoamine oxidase-A and CYP3A4 to the metabolic clearance of almotriptan. Although ketoconazole has a greater effect on almotriptan clearance than verapamil, no dosage adjustment is required when almotriptan is given with these drugs.