TABLE 6

Products, inhalers, and characteristics of muscarinic acetylcholine receptor antagonists

Table compiled based on reviews: Eglen, 2012, Cazzola et al., 2012, Matera and Cazzola, 2016, Williams and Rubin, 2018, Chabicovsky et al., 2019, Prescribing information USA and EU countries.

Active IngredientIndication (Brand)aInhalerDelivered DosePharmacological ProfileClinical Summary
Ipratropium (bromide-mono-hydrate)Maintenance treatment of COPD (USA,
EU), 2nd line in asthma (age ≥ 6 y) (EU)
Atrovent HFA and generics
pMDI20 µg/puff (ipr.br-hydr.) 1–2 puffs, 3–4 ×/dayFast M3 receptor dissociation
(t1/2=0.22h)b, low lipid solubilityc
SAMA
Duration of action <6 hours, in chronic treatment less effective than LABA or LAMA, maintenance treatment of symptoms in COPD
Additional bronchodilator in asthma
Indication as above Atrovent UDV and genericsUDV/Nebulizer250 µg/ml (ipr.br.-hydr.) 500 µg/2 ml
One inhalation, 3–4 ×/day
As above, for patients preferring nebulizer
Tiotropium (bromide)Maintenance treatment of COPD
Spiriva HandiHaler and generics
Single dose DPI10 µg (tio), 1 inhalation QDHighly potent, kinetic receptor subtype selective M3 > M1 >> M2, slow M3-receptor dissociation (t1/2= 27h)b, low lipid solubilityc,
predominantly eliminated via renal excretiond, LAMA
Airflow, symptoms, dyspneag and HRQoLh improved, reduction in exacerbationsi, extensive safety and efficacy database up to 4 years
Indication COPD as above and severe asthma (age ≥ 6 y)
Spiriva Respimat
Multidose SMI1.25µg or 2.5µg (tio)/actuation, 2 actuations QD
(lower dose = asthma in USA)
Equivalent to Spiriva HandiHaler in COPD. Severe asthma: add-on treatment of patients symptomatic on LABA-ICS (reduced exacerbations)
Glycopyrronium (bromide)Maintenance treatment of COPD
Seebri Neohaler (USA)
discontinued component of BID
combinations
Single dose DPI15.6µg (gly-br) 1 inhalation BIDHighly potent, kinetic receptor subtype selective M3 > M1 >> M2, modestly slow M3 receptor dissociation (t1/2=6.1h)b o.d. posology with higher daily dose, low lipid solubilityc, predominantly cleared renally, LAMAAirflow and symptoms improved, HRQoLh improved in one of two Ph III studies
Indication as above Seebri Breezhaler (EU)Single dose DPI55µg (gly-br), 1 inhalation QDFull bronchodilator effect with 1st dose, airflow, symptoms and HRQoLh improved, reduction of exacerbationsi
Indication as above Lonhala Magnair (USA)UDV/Nebulizer25µg (gly-br)/ ml,
1 inhalation BID
As above, for patients preferring nebulizer
Aclidinuim (bromide)Maintenance treatment of COPD
Tudorza Pressair (USA)
Eklira / Bretaris Genuair (EU)
Multidose DPI322µg (acl)
1 inhalation BID
Highly potent, kinetic receptor subtype selective M3 >∼ M1 >M2, modestly slow M3- receptor dissociation (t1/2=10.7 h)b, low lipid solubilityc, rapid hydrolytic inactivation, LAMAFull bronchodilator effect with 1st dose, airflow, symptoms, dyspneag and HRQoLh improved, reduction in exacerbationsi, long-term safety study up to 3 years in cardio-/cerebro-vascular risk population
Ume-clidinium (bromide)Maintenance treatment of COPD
Incruse Ellipta (USA, EU)
Rolufta Ellipta (EU)
Multidose DPI55µg (ume)
1 inhalation QD
Highly potent, kinetic receptor subtype selec- tive M3 >> M2, (M1 not published), slow M3 receptor dissociation (t1/2=1.37 h, tiotropium 4.55 h)e, low lipid solubilityc, hepatic metabolism and clearance, LAMAAirflow, symptoms, and HRQoLh improved, reduction in exacerbationsi indirectly shown by superiority of umeclidinium/vilanterol/fluticasone vs. vilanterol/fluticasone
RevefenacinMaintenance treatment of COPD
Yulperi (USA)
UDV/PARI
Nebulizer (recommended)
175µg/3ml
1 inhalation QD
Highly potent, kinetic receptor subtype selective M3>>M2 (M1 not published), slow receptor dissociation (t1/2= 1.35 h [tiotropium 3.83h, glycopyrronium 0.42h]f, LAMAAirflow and symptoms improved, HRQoLh improved in one of two Ph III studies. For patients preferring nebulizer
  • aThe brand names are not meant to be an exhaustive list; they are provided for illustrative purposes, as different products containing the same drugs may have different quantitative compositions, formulations, devices, and overall characteristics.

  • bCasarosa et al., 2010.

  • cLow lipid solubility = low and slow intestinal and mucosal absorption as well as penetration of blood-brain barrier.

  • dPrice et al, 2009.

  • eSalmon et al., 2013, Babu and Morjaria, 2017.

  • fHedge et al., 2018.

  • gAssessed by transition dyspnea index (TDI).

  • hBy St. Georges Respiratory Questionnaire (SGRQ).

  • iModerate–severe exacerbations.