Formoterol

Formoterol
	Formoterol (top),; (R,R)-(−)-formoterol (center) and; (S,S)-(+)-formoterol (bottom)
Clinical data
Trade names	Oxeze, Foradil, Symbicort, others
AHFS/Drugs.com	Monograph
License data	EU EMA: by formoterol fumarate dihydrate;
Pregnancy; category	AU: B3; ;
Routes of; administration	Inhalation (capsules for oral inhalation, DPI, MDI)
ATC code	R03AC13 (WHO) R03CC15 (WHO);
Legal status
Legal status	AU: S4 (Prescription only); NZ: Prescription only; UK: POM (Prescription only); US: ℞-only; EU: Rx-only; In general: ℞ (Prescription only);
Pharmacokinetic data
Protein binding	61% to 64%
Metabolism	Liver demethylation and glucuronidation (CYP2D6, CYP2C19, CYP2C9 and CYP2A6 involved)
Elimination half-life	10 h
Excretion	Kidney and fecal
Identifiers
	IUPAC name (RR,SS)-N-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl) propan-2-ylamino]ethyl] phenyl]formamide;
CAS Number	73573-87-2 ;
PubChem CID	3083544; 3034756;
IUPHAR/BPS	3465;
DrugBank	DB00983 ;
ChemSpider	2340731 ;
UNII	5ZZ84GCW8B;
KEGG	D07990 ;
ChEBI	CHEBI:408174 ;
ChEMBL	ChEMBL1363 ;
CompTox Dashboard (EPA)	DTXSID20860603 DTXSID1023077, DTXSID20860603 ;
ECHA InfoCard	100.131.654
Chemical and physical data
Formula	C19H24N2O4
Molar mass	344.411 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES O=CNc1cc(ccc1O)[C@@H](O)CN[C@H](C)Cc2ccc(OC)cc2;
	InChI InChI=1S/C19H24N2O4/c1-13(9-14-3-6-16(25-2)7-4-14)20-11-19(24)15-5-8-18(23)17(10-15)21-12-22/h3-8,10,12-13,19-20,23-24H,9,11H2,1-2H3,(H,21,22)/t13-,19+/m1/s1 ; Key:BPZSYCZIITTYBL-YJYMSZOUSA-N ;
	(verify)

Formoterol, also known as eformoterol, is a long-acting β₂ agonist (LABA) used as a bronchodilator in the management of asthma and chronic obstructive pulmonary disease (COPD). Formoterol has an extended duration of action (up to 12 h) compared to short-acting β₂ agonists such as salbutamol (albuterol), which are effective for 4 h to 6 h. Formoterol has a relatively rapid onset of action compared to other LABAs, and is effective within 2-3 minutes.^[2] The 2022 Global Initiative for Asthma report ^[3] recommends a combination formoterol/inhaled corticosteroid inhaler as both a preventer and reliever treatment for asthma in adults. In children, a short-acting β₂ adrenergic agonist (e.g., salbutamol) is still recommended.

It was patented in 1972 and came into medical use in 1998.^[4] It is available as a generic medication.^[5] It is also marketed in the combination formulations budesonide/formoterol and mometasone/formoterol.

Side effects

In November 2005, the US Food and Drug Administration (FDA) released a health advisory alerting the public to findings that show the use of long-acting β₂ agonists could lead to a worsening of wheezing symptoms in some patients.^[6]

Nowadays, available long-acting β₂ agonists include salmeterol, formoterol, bambuterol, and sustained-release oral salbutamol.

Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread – combination preparations include fluticasone/salmeterol and budesonide/formoterol.

Mechanism of action

Inhaled formoterol works like other β₂ agonists, causing bronchodilation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma.

Society and culture

Brand names

Formoterol is marketed in three forms: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI) and an inhalation solution, under various brand names including Atock, Atimos/Atimos Modulite, Foradil/Foradile, Fostair, Oxeze/Oxis, Perforomist and Symbicort.

Foradil/Foradile capsules for oral inhalation (Schering-Plough in the U.S., Novartis rest of world)
Oxeze/Oxis Turbuhaler dry-powder inhaler (DPI) (AstraZeneca)
Atock (Astellas)
Atimos/Atimos Modulite metered-dose inhaler (MDI) (Chiesi)
Perforomist inhalation solution (Mylan N.V.)
Symbicort Turbuhaler dry-powder inhaler (DPI) (AstraZeneca)

In some countries, Perforomist is marketed by Viatris after Upjohn merged with Mylan to create Viatris.^[7]^[8]

Uses and combinations

Arformoterol ((R,R)-(−)-formoterol) — an enantiopure compound used in the management of COPD
Combination drugs:

References

^ "List of nationally authorised medicinal products" (PDF). ema.europa.eu. Retrieved 17 June 2023.
^ Anderson GP (1993). "Formoterol: pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective beta 2-adrenoceptor agonist bronchodilator". Life Sci. 52 (26): 2145–60. doi:10.1016/0024-3205(93)90729-m. PMID 8099696.
^ Global Initiative for Asthma (2022). Global Strategy for Asthma Prevention and Management (Updated 2022) (PDF) (Report).
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 543. ISBN 9783527607495.
^ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.
^ "Advair Diskus, Advair HFA, Brovana, Foradil, Perforomist, Serevent Diskus, and Symbicort Information (Long Acting Beta Agonists)". U.S. Food and Drug Administration (FDA). Archived from the original on 1 November 2017. Retrieved 16 December 2019.
^ "Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan". Pfizer. 16 November 2020. Retrieved 17 June 2024 – via Business Wire.
^ "Brands". Viatris. 16 November 2020. Retrieved 17 June 2024.

[1] "List of nationally authorised medicinal products" (PDF). ema.europa.eu. Retrieved 17 June 2023.

[pmid8099696-2] Anderson GP (1993). "Formoterol: pharmacology, molecular basis of agonism, and mechanism of long duration of a highly potent and selective beta 2-adrenoceptor agonist bronchodilator". Life Sci. 52 (26): 2145–60. doi:10.1016/0024-3205(93)90729-m. PMID 8099696.

[3] Global Initiative for Asthma (2022). Global Strategy for Asthma Prevention and Management (Updated 2022) (PDF) (Report).

[Fis2006-4] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 543. ISBN 9783527607495.

[5] "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.

[6] "Advair Diskus, Advair HFA, Brovana, Foradil, Perforomist, Serevent Diskus, and Symbicort Information (Long Acting Beta Agonists)". U.S. Food and Drug Administration (FDA). Archived from the original on 1 November 2017. Retrieved 16 December 2019.

[7] "Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan". Pfizer. 16 November 2020. Retrieved 17 June 2024 – via Business Wire.

[8] "Brands". Viatris. 16 November 2020. Retrieved 17 June 2024.

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