key: cord-0887046-me4tdzvl
authors: Shabani, Minoosh; Shokouhi, Shervin; Moradi, Omid; Saffaei, Ali; Sahraei, Zahra
title: Tocilizumab Administration in Patients with SARS‐CoV‐2 Infection: Subcutaneous Injection versus Intravenous Infusion
date: 2020-06-03
journal: J Med Virol
DOI: 10.1002/jmv.26124
sha: 61081eec2ce7b17fd83fa6b418d3e9dbfe4a03e8
doc_id: 887046
cord_uid: me4tdzvl

Recent studies have revealed that cytokine storm syndrome, which is caused by the activation of inflammatory cytokines, is a likely underlying pathophysiology in patients with severe COVID‐19 that has been associated with a high mortality rate(1). This article is protected by copyright. All rights reserved.

Xiaoping Zhang et al. conducted a study in 2010 in which they evaluated the pharmacokinetics of subcutaneous administration of tocilizumab, following a single dose injection in healthy volunteers. They found that the area under the concentrationtime curve in volunteers who received tocilizumab at a dose of 162 mg through the intravenous route was 4340 ± 1360 µg×h/mL and that in volunteers who received tocilizumab at a dose of 162 mg through the subcutaneous route was 2370 ± 1240 µg×h/mL (mean ± SD). The time to maximum observed plasma concentration was 1.5 and 72 hour (median) in the intravenous and subcutaneous groups, respectively.

Hence, a coefficient of 1.8 may be acceptable for converting the intravenous dose to subcutaneous dose. However, they found that the pharmacodynamic properties of tocilizumab, which is responsible for its clinical effects, at a dose of 162 mg in both routes are similar. This suggests that there may be no need for dose conversion 4 .

Considering the abovementioned parameters, it can be concluded that administration of tocilizumab at a dose of 400 mg through the intravenous route (desired dose) may be equivalent to 400 mg tocilizumab through the subcutaneous route, despite the pharmacokinetic differences. This suggested dosing should be interpreted with caution due to individual pharmacokinetic variation 5 . Mentioned study also was done in healthy people. For example, in critically ill patients, the absorption process may be alter due to edema, shock state, etc.

Also, Mazzitelli et al., reported three patients with COVID-19 pneumonia who were treated with tocilizumab through subcutaneous route. In their study, tocilizumab was administered at a single dose of 162 mg through subcutaneous route. They found that the efficacy and safety of subcutaneous tocilizumab at single dose of 162 mg is comparable to intravenous route (8 mg/kg with a second dose 12 hours after the first

COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet

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Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA)

Pharmacokinetics and pharmacodynamics of tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, following single-dose administration by subcutaneous and intravenous routes to healthy subjects

Drug absorption, distribution, metabolism and excretion considerations in critically ill adults

Use of subcutaneous tocilizumab in patients with COVID-19 pneumonia

This article is protected by copyright. All rights reserved.