Almotriptan: a review of 20 years’ clinical experience

Figures & data

Table 1. Pharmacokinetic properties of almotriptan.

Parameter	Value/Description
Oral bioavailability	70%
Cmax	45 ng/mL for a single oral dose of 12.5 mg ≥75% of Cmax is achieved within 1 hour
Tmax	1.5–4.0 hours
AUC0∞	250–300 ng/mL∙hour (12.5 mg single oral dose)
Volume of distribution	195 L
Protein binding	<40%
Lipophilicity	logD(pH)7.4: −2.1
t1/2	3.0–3.6 hours
Elimination	45–50% excreted unchanged in urine within 24 hours (partly via active tubular secretion) <5% excreted unchanged in feces Remainder metabolized into inactive metabolites (by monoamine oxidase, cytochrome P450 isozymes 3A4 and 2D6, and flavin mono-oxygenase)
Pharmacokinetic drug interactions	No clinically relevant interactions with verapamil, propranolol, ketoconazole, fluoxetine, moclobemide or alcohol

AUC_0∞ = area under the plasma concentration–time curve from time zero to infinity; C_max = peak plasma concentration; T_max = time to C_max; t_1/2: elimination half-life.

Data taken from [15,18–22].

Table 2. Randomized, double-blind, controlled trials of almotriptan for the treatment of patients with moderate/severe migraine with or without aura: 2-h pain relief and 2-h pain free rates.

Trial	N	Treatment^a	2-h pain relief	2-h pain free	Tolerability
Pascual et al. (2000) [30]	722	A 6.25 or 12.5 mg or placebo	A 6.25: 60%* A 12.5: 70%* P: 38%	A 6.25: 29.9%* A 12.5: 38.8%* P: 15.5%	Well-tolerated, similar rate of AEs vs placebo
Dahlöf et al. (2001) [31]	742	A 2, 6.25, 12.5, or 25 mg or placebo	A 2: 30% A 6.25: 56.3%* A 12.5: 58.5%* A 25: 66.5%* P: 32.5%		Well-tolerated; doses of 2, 6.25 and 12.5 mg similar rate of AEs vs placebo
Dowson et al. (2002) [32]	668	A 12.5 or 25 mg or sumatriptan 100 mg or placebo	Overall: A 12.5: 56.8%* A 25: 56.5%* S 100: 63.7%* P: 42.4% Moderate baseline pain: A 12.5: 72.0%* A 25: 66.7%* S 100: 73.9%* P: 46.3% Severe baseline pain: A 12.5: 41.1%* A 25: 44.2%* S 100: 50.0%* P: 34.4%	Moderate baseline pain: A 12.5: 38.7%* A 25: 46.7%* S 100: 36.9%* P: 16.4% Severe baseline pain: A 12.5: 16.7%* A 25: 19.8%* S 100: 29.3%* P: 12.5%	A well-tolerated and associated with significantly fewer AEs vs sumatriptan (8.7% vs 22.2%, p < 0.001)
Spierings et al. (2001) [33]	1173	A 12.5 mg or sumatriptan 50 mg	A 12.5: 58.0% S 50: 57.3% (NS)	17.9 versus 24.6% (p = 0.005)	Treatment-emergent AEs in 9.1% vs 15.5% (p = 0.001)
Goadsby et al. (2007) [34]	1061	A 12.5 mg or zolmitriptan 2.5 mg	A 12.5: 65.4% Z 2.5: 70.2% (NS)	A 12.5: 43.5% Z 2.5: 48.3% (NS)	Similar rate of treatment-emergent AEs vs zolmitriptan
Láinez et al. (2007) [35]		A 12.5 mg or ergotamine 2 mg/caffeine 200 mg	A 12.5: 57.7% E/C: 44.5% (p < 0.01)	A 12.5: 20.9% E/C: 13.7% (p < 0.05)	AEs reported by 16 almotriptan recipients vs 27 ergotamine/caffeine recipients

a Single oral doses unless indicated otherwise.

* p < 0.05 vs placebo.

A = almotriptan; AE = adverse event; P = placebo; N = number of patients; NS = not significant; S = sumatriptan; Z = zolmitriptan.

Table 3. Randomized controlled trials of early treatment of acute migraine (with or without aura) with almotriptan 12.5 mg.

Trial/Study design	N	Treatment	Results
AIMS [47] M, CR, OL	1450	Early (<1 h from pain onset) vs standard (moderate/ severe pain)	Early vs standard Median headache duration: 3.18 vs 5.53 h (p < 0.001). 2-h pain free (according to pain intensity at onset and time since onset): <1 h from onset: mild/mod 54% vs severe 18% (p < 0.001); >1 h from onset: mild/mod 37% vs severe 23% (NS). Sustained pain free (according to pain intensity at onset and time since onset): <1 h from onset: mild/mod 24% vs severe 8% (p < 0.076); >1 h from onset: mild/mod 13% vs severe 7% (NS).
AEGIS [48,51] M, R, DB	378	ALT vs placebo; both taken <1 h of onset	ALT vs placebo 2-h pain relief: 72.3% vs 48.4% (p < 0.001); 2-h pain free: 37.0% vs 23.9% (p = 0.01); Sustained pain free: 24.7% vs 16.1% (p = 0.04).
AwM [49,52] M, R, DB	403	ALT early (mild and <1 h) vs ALT standard (moderate/severe pain) vs placebo early vs placebo standard	ALT early/mild vs ALT standard 2-h pain free: 53% vs 37.5% (p = 0.02); Sustained pain free: 45.6% vs 30.5% (p = 0.02); Placebo early/mild vs placebo standard: 24.7% vs 17.5% (p ≤ 0.01 vs respective ALT arms).
Bartolini et al. [50] M, R, DB, CO	133	ALT 12.5 mg vs frovatriptan 2.5 mg	ALT vs frovatriptan 2-h pain relief: 56% vs 54% (NS); 2-h pain free: 32% vs 30% (NS); Sustained pain free: 18% vs 21% (NS).

ALT = almotriptan; CO = crossover; CR = cluster randomized; DB = double-blind; M = multicenter; OL = open = label; N = number of patients; NS = not statistically significant; R = randomized.

Figure 1. Efficacy of almotriptan 12.5 mg in the treatment of menstrual migraine: 2 h pain free rate (primary endpoint) and 24 h pain free rate from a randomized double-blind, placebo-controlled study [77].

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