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(Updated March 31, 2020)
Mechanism of Action: Bacteriostatic activity through inhibition of dependent protein synthesis by reversibly binding to the 50S subunit of ribosomes; this blocks the transpeptidation/translocation step of protein synthesis.(1) Proposed immunomodulatory effects against Zika and Ebola virus. In vitro, azithromycin suppresses Zika virus by upregulating host type I and III interferons and downstream interferon-stimulated genes. Azithromycin upregulates expression of innate immune receptors, MDA5 and RIG-I, and upregulates phosphorylation of TBK1 and IRF3.(2) The 50% effective concentrations (EC50) of azithromycin in vitro for Ebola is 2.79M.(3) The EC50 of azithromycin in vitro for Zika virus ranges from 2.1-5.1M.(4) As of March 25 2020, no in vitro data is available for SARS-CoV-1 or SARS-CoV-2.
Small, open-label non-randomized study evaluated synergistic effect of azithromycin used in combination with hydroxychloroquine for SARS-CoV-2 measured virological clearance (negative nasopharyngeal PCR) at day 6 (not a clinical endpoint such as mortality or ICU admission). Six out of six patients (100%) treated with hydroxychloroquine and azithromycin were virologically cured compared with hydroxychloroquine monotherapy (57.1%) and control (12.5%) p<0.001.(5) Given the limited data with azithromycin in the treatment of COVID-19, more studies are needed to determine clinical effectiveness.
Experimental and off-label use in SARS-CoV-2 (COVID-19)
Clinically Significant Drug Interactions
Adverse Effects: Loose stools, vomiting, diarrhea, nausea. Elevated LFTs less common. QT prolongation, hepatotoxicity, SJS/TENS, DRESS are rare(7)
Monitoring Parameters: Baseline EKG (QTc prolongation), liver function tests, CBC with differential(7)
Pharmacokinetics: Parameters were similar in healthy older adults (65 – 85 years) compared to young adults, although in older women, Cmax was increased by 30-50%. Significant accumulation was not observed(6)
Absorption: Oral bioavailability 37%, Tmax: 2-3 hours(7),(10)
Distribution: Vd: 31-33L/kg (lipophilic).(7) Extensive tissue, distributes well into skin, lungs, sputum, tonsils, and cervix, compared to significantly lower serum concentrations.(11) Poor penetration into CSF.(7) High and persistent concentrations in bronchial secretions.(11) Protein binding: 7-50% (concentration dependent).(11)
A small study of steady-state pulmonary disposition of azithromycin in older adults recorded average concentrations of 1.14M in extracellular tissue and 261.4M in intracellular tissue, over a 24-hr dosing interval.(14)
Metabolism: minimally metabolized by CYP3A4 (does not inhibit or induce)(7)
Excretion: 6% -14% unchanged in urine, mostly excreted unchanged in the bile mainly by ABCB1 and MRP2 (encoded by the gene ABCC2)(11)
COVID-19 is an emerging, rapidly evolving situation. Get the latest from CDC: https://www.coronavirus.gov and NIH: https://www.nih.gov/coronavirus and the Liverpool drug interaction group: http://www.covid19-druginteractions.org
This document is for informational purposes only and is not intended as, and should not be interpreted as, medical advice or other professional advice. Clinical judgement is still required. GeriMedRisk does not endorse the use of any of these therapies for COVID, but offers this information in the hopes of decreasing the risk of harmful drug-drug interactions or adverse drug events. We will do our best to update this information.
|Last updated: March. 31, 2020 - 12:06 PM||Back to COVID-19 Resources|