関: almotriptan malate

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/04/13 21:20:34」(JST)

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Almotriptan (trade names Axert (US, Canada), Almogran (Belgium, Denmark, Finland, France, Germany, Italy, Ireland Portugal, Spain, the United Kingdom, the Netherlands, Sweden, Switzerland, South Korea… ), Almotrex (Italy) and Amignul (Spain)) is a triptan drug discovered and developed by Almirall for the treatment of heavy migraine headache. It is available in 12.5 mg in most countries and also 6.25 mg in US and Canada.

Indications

Almotriptan is prescribed to treat the acute headache phase of migraine attacks with or without aura.^[1]
Almotriptan is the only oral triptan approved in the USA for the treatment of migraine in adolescent from 12 to 17 years of age.

Mechanism of action

Almotriptan has a high and specific affinity for serotonin 5-HT_1B/1D receptors. Binding of the drug to the receptor leads to vasoconstriction of the cranial blood vessels and thus affects the redistribution of cranial blood flow. Almotriptan significantly increases cerebral blood flow and reduces blood flow through extracerebral cranial vessels. Even though it affects cranial blood vessels a single dose of almotriptan (12.5 mg) has no clinically significant effect on blood pressure or heart rate in both young and elderly healthy volunteers. However larger doses seem to slightly increase blood pressure but not beyond clinical relevance.^[2]

Pharmacokinetics

Almotriptan has a linear pharmacokinetic up to 200 mg dose. Its half life is 3 hours and nearly 70% bioavailability.
C_max is observed 1.5–4 hours after oral administration and approximately 50% of the drug is excreted unchanged in the urine. Metabolism is mediated through MAO-A and CYP3A4 and CYP2D6 oxidation. Almotriptan clearance is moderately reduced in the elderly but does not require dose adjustment. Sex does not alter the pharmacokinetics of the drug. However, patients with moderate-to-severe renal dysfunction should limit their total daily dose to 12.5 mg. ^[3]

Drug interactions

As mentioned previously almotriptan is metabolized mainly by MAO-A and to lesser extent by CYP3A4 and CYP2D6. Studies of drugs used as preventive against migraine (propranolol and verapamil), anti-depressants (moclobemide and fluoxetine) yielded results that showed significant altering of the pharmacokinetics of almotriptan though they were deemed not clinically relevant.^[2]

Efficacy

The efficacy and tolerability of almotriptan has been studied in numerous randomised, control-led trials totaling more than 4800 adults with either moderate or severe attacks of migraine. Its efficacy is significantly more effective than placebo and alleviates nausea, photophobia and phonophobia linked to migraine attacks. Compared to other triptan drug, 12.5 mg of almotriptan has similar efficacy as 50 mg of sumatriptan and fewer adverse effects.^[2]

Contraindications

(see SmPC) Hypersensitivity to the active substance or to any of the excipients.
As with other 5-HT1B/1D receptor agonists, almotriptan should not be used in patients with a history, symptoms or signs of ischaemic heart disease (myocardial infarction, angina pectoris, documented silent ischaemia, Prinzmetal’s angina) or severe hypertension and uncontrolled mild or moderate hypertension.
Patients with a previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA). Peripheral vascular disease.
Concomitant administration with ergotamine, ergotamine derivatives (including methysergide) and other 5-HT1B/1D agonists is contraindicated.
Patients with severe hepatic impairment.

Side effects

(see SmPC) Almotriptan has proved to have an adverse effects profile similar to placebo when used following the Summary of Product Characteristics instructions (see references).

"For rare adverse events, please refer to the manufacturer´s webpage"

References

Early vs. non-early intervention in acute migraine-'Act when Mild (AwM)'. A double-blind, placebo-controlled trial of almotriptan. Goadsby PJ et al., Cephalalgia. 2008 Apr;28(4):383-91
Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. MD Ferrari et al., (Cephalalgia 2002; 22:633-658)
Almotriptan is effective and well tolerated in migraine patients who respond poorly to oral sumatriptan: A double-blind, randomized trial, Diener HC (Headache. 2005 Jul-Aug;45(7):874-82)
Triptans and CNS side effects: pharmacokinetic and metabolic mechanisms. DW Dodick et al. Cephalalgia. 2004 Jun;24(6):417-24
Triptans and chest symptoms: the role of pulmonary vasoconstriction. DW Dodick (Cephalalgia, 2004,24, 298–304)
Almotriptan improves response rates when treatment is within 1 hour of migraine onset. AJ Dowson et al., (Headache 2004; 44: 318-322)
A long-term open-label study of oral almotriptan 12.5 mg for the treatment of acute migraine. NT. Mathew; for the Oral Almotriptan Study Group (Headache. 2002;42:32-40)
Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial. AJ Dowson et al. (Cephalalgia 2002; 22, 453-461)
Tolerability and efficacy of almotriptan in the long-term treatment of migraine, J. Pascual et al. (Eur Neurol 2001;45:206-213)
Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study. J. Pascual et al. Cephalalgia. 2000;20:588-596
Almotriptan in the treatment of migraine attacks in clinical practice: results of the TEA 2000 observational study, Pascual J et al., Neurologia. 2003 Jan-Feb;18(1):7-17.
Early intervention with almotriptan: results of the AEGIS trial (AXERT Early Migraine Intervention Study). Mathew et al., Headache. 2007 Feb;47(2):189-98
Evaluation of efficacy, tolerability, and treatment satisfaction with almotriptan in 3 consecutive migraine attacks. The migraine—satisfaction with treatment: reality with Almogran study. Massiouu H et al., Eur Neurol. 2006;55(4):198-203
Triptans in the treatment of migraine: drug selection by means of the SOJA method Expert Opin Pharmacother. Janknegt J,2007 Oct;8 Suppl 1:S15-30
Patient preference in migraine therapy. A randomized, open-label, crossover clinical trial of acute treatment of migraine with oral almotriptan and rizatriptan Díez FI et al., J Neurol. 2007 Feb;254(2):242-9
Use of the sustained pain-free plus no adverse events endpoint in clinical trials of triptans in acute migraine. Dodick DW et al. CNS Drugs. 2007;21(1):73-82
A pharmacoeconomic evaluation of oral triptans in the treatment of migraine in Italy. Gori S. et al. Minerva Med. 2006 Dec;97(6):467-77
Management costs of chest and CNS-related adverse events associated with the treatment of acute migraine attacks with oral triptans. Slof J et al., Neurologia. 2005 Jul-Aug;20(6):290-8
Efficacy, speed of action and tolerability of almotriptan in the acute treatment of migraine: pooled individual patient data from four randomized, double-blind, placebo-controlled clinical trials. Dahlöf CG et al. Cephalalgia 2006;26:400–408
Characteristics of migraine attacks and responses to almotriptan treatment: a comparison of menstrually related and nonmenstrually related migraines. Diamond ML et al., Headache 2008;48:248–258

External links

R&D page by Almirall Prodesfarma
Axert Official homepage by Ortho-McNeil
Axert prescribing information

References

^ "Almotriptan Facts and Comparisons". Drugs.com. Retrieved 7 October 2012.
^ ^a ^b ^c Keam, SJ; Goa, KL; Figgitt, DP (2002). "Almotriptan: a review of its use in migraine.". Drugs 62 (2): 387–414. doi:10.2165/00003495-200262020-00010. PMID 11817980.
^ McEnroe, JD; Fleishaker, JC (2005). "Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor agonist for the treatment of migraine.". Clinical pharmacokinetics 44 (3): 237–46. doi:10.2165/00003088-200544030-00002. PMID 15762767. |accessdate= requires |url= (help)

UpToDate Contents

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1. 成人における片頭痛の急性期治療 acute treatment of migraine in adults
2. 小児における片頭痛の急性期治療 acute treatment of migraine in children
3. 性行為に伴う一次性頭痛 primary headache associated with sexual activity
4. 患者情報：成人における片頭痛（詳細） migraine headaches in adults beyond the basics
5. 患者情報：小児における頭痛（詳細） headache in children beyond the basics

English Journal

Efficacy of frovatriptan as compared to other triptans in migraine with aura.

Evers S1, Savi L, Omboni S, Lisotto C, Zanchin G, Pinessi L.
The journal of headache and pain.J Headache Pain.2015 Dec;16:514. doi: 10.1186/s10194-015-0514-8. Epub 2015 Apr 1.
BACKGROUND: The treatment of migraine attacks with aura by triptans is difficult since triptans most probably are not efficacious when taken during the aura phase. Moreover, there are insufficient data from randomised studies whether triptans are efficacious in migraine attacks with aura when taken
PMID 25916333

Acute Migraine Treatment.

Becker WJ.
Continuum (Minneapolis, Minn.).Continuum (Minneap Minn).2015 Aug;21(4 Headache):953-72. doi: 10.1212/CON.0000000000000192.
PURPOSE OF REVIEW: This article provides a systematic, evidence-based approach to acute medication choices for the patient with migraine.RECENT FINDINGS: Recent clinical trials, meta-analyses, and practice guidelines have confirmed that four nonsteroidal anti-inflammatory drugs (NSAIDs) with randomi
PMID 26252584

Acute Migraine Treatment in Adults.

Becker WJ1,2.
Headache.Headache.2015 Jun;55(6):778-93. doi: 10.1111/head.12550. Epub 2015 Apr 15.
There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office-based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature
PMID 25877672

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リンク元	「アルモトリプタン」
拡張検索	「almotriptan malate」

「アルモトリプタン」

Almotriptan
Systematic (IUPAC) name
	N,N-dimethyl-2- [5-(pyrrolidin-1-ylsulfonylmethyl)- 1H-indol-3-yl]-ethanamine
Clinical data
Trade names	Axert
AHFS/Drugs.com	monograph
MedlinePlus	a603028
Pregnancy; category	US: C (Risk not ruled out);
Legal status	Prescription only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	70%
Protein binding	35%
Metabolism	Hepatic
Half-life	3–4 hours
Identifiers
CAS Registry Number	154323-57-6
ATC code	N02CC05
PubChem	CID 123606
DrugBank	DB00918
ChemSpider	110198
UNII	1O4XL5SN61
KEGG	D02824
ChEBI	CHEBI:520985
ChEMBL	CHEMBL1505
Chemical data
Formula	C17H25N3O2S
Molecular mass	335.465 g/mol
	SMILES O=S(=O)(N1CCCC1)Cc3cc2c(cnc2cc3)CCN(C)C;
	InChI InChI=1S/C17H25N3O2S/c1-19(2)10-7-15-12-18-17-6-5-14(11-16(15)17)13-23(21,22)20-8-3-4-9-20/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3 ; Key:WKEMJKQOLOHJLZ-UHFFFAOYSA-N ;
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