NAC in COVID Dosing

Inpatient protocol = 150 mg/kg/day divided q4hrs (25 mg/kg q4hrs rounded up to nearest 600 mg)

Why 150 mg/kg/day:

  • NAC dosing calculations based on replacing glutathione (GSH) turnover in patients with acetaminophen (APAP) toxicity = 6 mg/kg/hr = NAC 144 mg/kg/day (Rumack & Bateman 2012)

      • FDA "safety factor" wanting NAC to increase PO protocol for APAP toxicity to PO NAC 420 mg/kg/day x 3 days (Rumack & Bateman 2012); IV protocol 300 mg/kg/day x 1 day

  • case report of adjuvant treatment of H1N1 pneumonia with NAC 100 mg/kg/day (Lai et al 2010)

Why rounded up to nearest 600 mg

  • ready availability of 600 mg capsules of acetylcysteine

Why q4hrs:

  • half-life of NAC ~5.5 hrs

70 kg patient receives 1800 mg q4hr = 10,800 mg/day


Outpatient protocol = 2400 mg x 1; then 1200 mg PO BID x 2 weeks

Reasoning

  • Dosing for attenuation of influenza symptoms = NAC 600 mg BID given prophylactically/longterm prior to contracting illness (De Flora et al 1997)

  • Dosing for longterm management of COPD/exacerbations = NAC 600 mg BID (Sanguetti 2016)

  • Increased dose to account for patients already being symptomatic; adjusted for inpatient calculations above

  • ready availability of 600 mg capsules of acetylcysteine

Outpatients take 1200 mg BID = 2400 mg/day



NAC Pharmacokinetics I: How Much (Dose)?

221 - Rumack Bateman 2012 02 APAP & NAC dose duration Past Present Future.pdf
Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: Past, present and future. Clin Tox. 2012. 50:91-98.
Lai et al - High-dose NAC for H1N1 - Ann Int Med May 2020 vol153(10).pdf
Lai KY, Ng WY, Osburga Chan PK, Wong KT, Cheng F. High-Dose N-Acetylcysteine Therapy for Novel H1N1 Influenza Pneumonia. Annals of Int Med. 2010. 152: 687.
De Flora et al 1997 Attenuation of influenza sxs with longterm NAC.pdf
De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J. 1997. 10: 1535-1541.
Sanguinetti NAC in COPD 2016.pdf
Sanguinetti C. N-acetylcysteine in COPD: why, how, and when? Multidisciplinary Respiratory Medicine. 2016. 11: 8.

NAC Pharmacokinetics II: How Often, How Long (Frequency/Duration)?

Borgstrom Kagedal 1990 - DOSE DEPENDENT PHARMACOKINETICS OF N-ACETYLCYSTEINE AFTER ORAL DOSING - 1990.pdf
Olsson B, Johansson M, Gabrielsson J, Bolme P. Pharmacokinetics and Bioavailability of Reduced and Oxidized N-Acetylcysteine. Eur J Clin Pharmacol. 1988. 34:77-82.
Holdness 1991 Clinical Pharmacokinetics of N-Acetylcysteine - holdiness MR 1991.pdf
Holdiness M. Clinical Pharmacokinetics of N-Acetylcysteine. Clin Pharmacokinet. 1991. 20:1 23-134.
Olsson et al 1988 Pharmacokinetics and Bioavailability of Reduced and Oxidized N-Acetylcysteine - olsson1988.pdf
Borgstrom L, Kagedal B. Dose Dependent Pharmacokinetics of N-Acetylcysteine After Oral Dosing to Man. Biopharmaceutics & Drug Disposition. 1990. 11: 131-136.