Formoterol

Not to be confused with Fenoterol.

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.

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[1] 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 Y
PubChem CID	3083544 3034756
IUPHAR/BPS	3465
DrugBank	DB00983 Y
ChemSpider	2340731 Y
UNII	5ZZ84GCW8B
KEGG	D07990 Y
ChEBI	CHEBI:408174 Y
ChEMBL	ChEMBL1363 Y
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 Y Key:BPZSYCZIITTYBL-YJYMSZOUSA-N Y
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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

Inhaler for a powder based in budesonide and formoterol

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:
  • Aclidinium bromide/formoterol
  • Budesonide/formoterol
  • Mometasone furoate/formoterol