Safety, tolerability, and pharmacokinetics of a 2 g subcutaneous dose of ceftriaxone as an alternative to intravenous delivery

Sep 30, 2026

Subcutaneous delivery of antibiotics is a practical alternative to intravenous administration. Ceftriaxone is widely used for multiple infections, but evidence on safety and pharmacokinetics for a 2 g subcutaneous dose is limited. A prospective, self-controlled cross-over study enrolled 20 stable inpatients receiving ceftriaxone; participants received an IV dose then a single 2 g SC dose. Pain, infusion-site reactions, and ceftriaxone concentrations were assessed over 24 hours, with pharmacokinetic modeling using nonlinear mixed-effects methods. Results show good tolerability, high estimated bioavailability, and lower peak with comparable trough levels versus IV, with similar target attainment for common hospitalized infections.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Importance

Clinical trial registration

Background and rationale

Materials and methods

Study design

| Antimicrobial Chemotherapy | Full-Length Text Safety, tolerability, and pharmacokinetics of a 2 g subcutaneous dose of ceftriaxone as an alternative to intravenous delivery Henco Nel,1 Fionnuala Murray,1 Okhee Yoo,2,3,4,5 Matthew Rawlins,6 Edward Raby,1,7 Madhu Page-Sharp,8 Brioni Moore,8 Sam Salman,2,8,9,10 Laurens Manning1,2,10 AUTHOR AFFILIATIONS See affiliation list on p. 9. ABSTRACT Subcutaneous delivery of antibiotics is a practical alternative to intravenous administration. Ceftriaxone is commonly used for a variety of infections with limited data on the safety and pharmacokinetics of a 2 g subcutaneous dose. This was a prospective, self-controlled cross-over study in 20 stable inpatients receiving ceftriaxone for their infection. Following an intravenous dose, participants received a single dose of 2 g subcutaneous ceftriaxone, in 50 mL normal saline via gravity feed. Capillary dried blood spots were collected at baseline, 1, 2, 4, 8, and 24 hours following the subcutaneous and intravenous doses. Pain scores and infusion site reactions (edema/erythema) were assessed. Ceftriaxone concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay. A population pharmacokinetic model was developed using nonlinear mixed-effects modeling. The highest median (interquartile range) pain score within the first 2 hours following infusion of a subcutaneous dose of 2 g ceftriaxone was 2.5 (1–4) . All participants were pain-free 4 hours after the infusion. The estimated bioavailability was 95.7%(95% bootstrap interval 90.3–99.5) . Compared with intravenous, subcutaneous administration resulted in lower peak and comparable trough concentrations. The probability of target attainment for free drug concentrations was similar to intravenous administration for most common infections in hospitalized patients. Subcutaneous administration of 2 g ceftriaxone is well tolerated and has a comparable pharmacokinetic profile relative to intravenous dosing in non-critically ill patients with severe infections. IMPORTANCE This prospective, self-controlled cross-over design study demonstrates that subcutaneous administration of 2 g ceftriaxone appears safe and well tolerated with a comparable pharmacokinetic profile relative to intravenous dosing in non-critically ill patients with severe infections. CLINICAL TRIALS This study was registered at ACTRN12624000692538 . KEYWORDS subcutaneous antibiotics, ceftriaxone, pharmacokinetics, safety, tolerability C eftriaxone is a third-generation parenteral cephalosporin used for treatment of hospitalized patients with a variety of infections including severe communityacquired pneumonia, urinary tract infections, intra-abdominal infections, and meningitis (1–3) . It is also commonly used in outpatient parenteral antimicrobial therapy (OPAT) settings due to its safety profile and once-daily dosing for most indications (4, 5) . Ceftriaxone is typically administered intravenously (IV) . Data supporting intramuscular (IM) administration are provided in the product information sheet, but due to injection-related pain, this route is infrequently used (6) . By contrast, subcutaneous (SC) Editor James E. Leggett, Providence Portland Medical Center, Portland, Oregon, USA Address correspondence to Laurens Manning, [laurens.manning@uwa.edu.au](laurens.manning@uwa.edu.au). authors declare conflict of interest administration is not currently recommended in clinical guidelines or by the manufacturers but may be better tolerated and have favorable pharmacokinetics. Administration of SC antibiotics has been practiced in Europe, particularly in France, for many years (4, 7, 8). The SC route has garnered increasing attention in recent years asa practical alternative to IV delivery, with increasing evidence in the literature supporting its safety and efficacy for various antibiotics (4, 9–13) . This route of administration offers an attractive alternative where IV a

FAQs

What was the study design and primary objective?

The study used a prospective, self-controlled cross-over design with pharmacokinetic data for both SC and IV administration for each participant. The primary objective was to establish tolerability of 2 g ceftriaxone SC using a numerical rating score for pain and local reactions.

How were pain and infusion-site reactions assessed?

Pain scores and infusion site reactions, including edema and erythema, were assessed after administration. Measurements were taken at baseline and at multiple timepoints following SC and IV dosing.

How did subcutaneous dosing compare with intravenous dosing pharmacokinetically?

Compared with intravenous administration, subcutaneous administration produced lower peak concentrations with comparable trough concentrations. The estimated bioavailability was reported as 95.7%, and target attainment probabilities for free drug concentrations were similar for most common infections in hospitalized patients.

Sep 30, 2026

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