. 2021 Dec 15;103:108412. doi: 10.1016/j.intimp.2021.108412

Table 1.

Summary of key characteristics of levocetirizine and montelukast.

Levocetirizine	Montelukast
• A leading H1 receptor antagonist in the world among more than 40 antihistamines • Considered an ideal, H1 receptor antagonist, ‘insurmountable’ by pharmacologists with a Vd 0.4 L/kg; ideal molecule Vd < 0.6 L/kg [23] • FDA approved for allergic rhinitis, chronic idiopathic urticaria (CIU) [41] • Pregnancy Category B [41] • Titratable with increasing efficacy demonstrated in CIU from 5 to 20 mg/day [42] • Only antihistamine in the world to independently improve quality of life across all domains (global health status SF-36; P < 0.001 for all scales) as well as decrease overall health-care costs in a series of 421 patients with allergy/asthma treated for six months [39] • More potent and safer than astemizole, the latter, a second-generation antihistamine with antiviral activity); astemizole was active against both SARS-CoV and MERS-CoV. Astemizole; however, was withdrawn from the US market in 1999 due to cardiac toxicity - prolongation of the QTc interval [43], [44], [45] • Cell and clinical science – antiviral activity against human rhinovirus-16 (HRV-16) [11]	• FDA approved for allergy, asthma, and exercise induced bronchospasm [46] • A leading leukotriene modulator in the world • Pregnancy Category B [46] • Titratable from 4 to 40 mg with linear pharmacokinetics to 50 mg/day [46] • Safety studies at 200 mg/day for 22 weeks; 900 mg/day for approximately one week [46], [47] • Ideal in COVID-19 acute care medicine where the lung is the target organ [48] • Given orally/nasogastric tube – improves FEV1: 15% in one to three hours [46] • Efficiently attenuates ARDS in a mouse model [28] • Antiviral activity (disrupting viral integrity) against Zika virus, Dengue virus, and yellow fever virus (like COVID-19 and Human rhinovirus (HRV), all are ssRNA viruses) [49] • Potential dual COVID-19 activity - main protease enzyme inhibition and virus entry into the host cell (Spike/ACE2) [34]

Levocetirizine

Montelukast

•
A leading H1 receptor antagonist in the world among more than 40 antihistamines
•
Considered an ideal, H1 receptor antagonist, ‘insurmountable’ by pharmacologists with a Vd 0.4 L/kg; ideal molecule Vd < 0.6 L/kg [23]
•
FDA approved for allergic rhinitis, chronic idiopathic urticaria (CIU) [41]
•
Pregnancy Category B [41]
•
Titratable with increasing efficacy demonstrated in CIU from 5 to 20 mg/day [42]
•
Only antihistamine in the world to independently improve quality of life across all domains (global health status SF-36; P < 0.001 for all scales) as well as decrease overall health-care costs in a series of 421 patients with allergy/asthma treated for six months [39]
•
More potent and safer than astemizole, the latter, a second-generation antihistamine with antiviral activity); astemizole was active against both SARS-CoV and MERS-CoV. Astemizole; however, was withdrawn from the US market in 1999 due to cardiac toxicity - prolongation of the QTc interval [43], [44], [45]
•
Cell and clinical science – antiviral activity against human rhinovirus-16 (HRV-16) [11]

•
FDA approved for allergy, asthma, and exercise induced bronchospasm [46]
•
A leading leukotriene modulator in the world
•
Pregnancy Category B [46]
•
Titratable from 4 to 40 mg with linear pharmacokinetics to 50 mg/day [46]
•
Safety studies at 200 mg/day for 22 weeks; 900 mg/day for approximately one week [46], [47]
•
Ideal in COVID-19 acute care medicine where the lung is the target organ [48]
•
Given orally/nasogastric tube – improves FEV1: 15% in one to three hours [46]
•
Efficiently attenuates ARDS in a mouse model [28]
•
Antiviral activity (disrupting viral integrity) against Zika virus, Dengue virus, and yellow fever virus (like COVID-19 and Human rhinovirus (HRV), all are ssRNA viruses) [49]
•
Potential dual COVID-19 activity - main protease enzyme inhibition and virus entry into the host cell (Spike/ACE2) [34]

Combination: Anti-inflammatory synergy between levocetirizine and montelukast in the downregulation of IL-4, IL-6, IL-8, TNF-alpha, GM-CSF, NF-kB, ICAM-1/sICAM-1, VCAM-1, and neutrophil/eosinophil quantity and migration[7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18].