Almotriptan

Almotriptan (trade name Axert and others) is a triptan medication discovered and developed by Almirall for the treatment of heavy migraine headache.

Almotriptan
Clinical data
Trade namesAxert
AHFS/Drugs.comMonograph
MedlinePlusa603028
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
  • US: ℞-only [1][2]
  • EU: Rx-only [3]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability70%
Protein binding35%
MetabolismLiver
Elimination half-life3–4 hours
Identifiers
IUPAC name
  • N,N-dimethyl-2- [5-(pyrrolidin-1-ylsulfonylmethyl)- 1H-indol-3-yl]-ethanamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H25N3O2S
Molar mass335.47 g·mol−1
3D model (JSmol)
SMILES
  • CN(C)CCc2c[nH]c3ccc(CS(=O)(=O)N1CCCC1)cc23
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 Y
  • Key:WKEMJKQOLOHJLZ-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

It was patented in 1992 and approved for medical use in 2000.[4]

Medical uses

Almotriptan is prescribed to treat the acute headache phase of migraine attacks with or without aura.[5] Almotriptan is the only oral triptan approved in the US for the treatment of migraine in adolescent from 12 to 17 years of age.

Efficacy

The efficacy and tolerability of almotriptan has been studied in numerous randomised, controlled 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. Almotriptan has similar efficacy as a standard dose of sumatriptan, another triptan drug, and fewer adverse effects.[6]

Contraindications

As with other triptans, 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. Other contraindications are previous cerebrovascular accident (CVA) or transient ischaemic attack (TIA), peripheral vascular disease, severe hepatic impairment, concomitant administration of ergotamine, ergotamine derivatives (including methysergide) and other 5-HT1B/D agonists.

Side effects

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

Pharmacology

Mechanism of action
Further information: Serotonin receptor agonist and Triptan § Mechanism_of_action

Like all triptans, almotriptan has a high and specific affinity for serotonin 5-HT1B/1D receptors. Binding of the drug to the receptor leads to vasoconstriction of the cranial (brain) blood vessels and thus affects the redistribution of 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 standard dose of almotriptan has no clinically significant effect on blood pressure or heart rate in both young and elderly healthy volunteers. Larger doses seem to slightly increase blood pressure but not beyond clinical relevance.[6]

Pharmacokinetics

Almotriptan has linear pharmacokinetics up to the 16-fold standard dose. Its biological half-life is 3 hours, and its bioavailability 70%. Cmax 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 the enzymes 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. People with moderate-to-severe renal dysfunction are recommended to use only half the dose.[7]

Interactions

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.[6]

Society and culture

Brand names

Brand names include Axert (US, Canada), Almogran (Belgium, Denmark, Finland, France, Germany, Italy, Ireland Portugal, Spain, the United Kingdom, the Netherlands, Sweden, Switzerland, South Korea...), Almotrex (Italy), Almozen (Bulgaria and Poland) and Amignul (Spain).

References
  1. "Almotriptan tablet, film coated". DailyMed. Retrieved 17 February 2021.
  2. "Axert- almotriptan malate tablet, coated". DailyMed. Retrieved 17 February 2021.
  3. "Active substance: almotriptan" (PDF). List of nationally authorised medicinal products. Europeans Medicines Agency. 11 February 2021.
  4. Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 531. ISBN 9783527607495.
  5. "Almotriptan Facts and Comparisons". Drugs.com. Retrieved 7 October 2012.
  6. 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. S2CID 242752549.
  7. 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): 237–246. doi:10.2165/00003088-200544030-00002. PMID 15762767. S2CID 23136754.
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