Original research Given the limitation of our study in storing the filled devices at room temperature, we would advise that clinicians wishing to use aciclovir in elastomeric devices in clinical practice should store these at a temperature below 20°C prior to use. Bearing in mind the good chemical stability shown by the drug, indi- vidual units may consider appropriate extrapolation of aciclovir stability to NHS YCD room temperature storage (up to 25°C) while assuring that the aciclovir concentration will remain above the 95% limit. CONCLUSIONS At the low concentration of 200 mg/240 mL and intermediate concentration of 2400 mg/240 mL (and other concentrations within that range) aciclovir saline solution is stable in Accu- fuser and Easypump II elastomeric infusion pumps for 14 days at room temperature and 24 hours of 32°C in-use temperature exposure. The data from this study provide critical support for increased use of aciclovir in OPAT in line with the wide clin- ical interest, particularly in the paediatric patient population. However, precipitation of aciclovir at the highest concentration tested (4500 mg/240 mL) at 32°C would preclude this high dose in any clinical setting. Author affiliations 1 University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia 2 NHS England, Birmingham, UK 3 Pharmacy Department, Nottingham University Hospitals, Nottingham, UK 4 Department of Pharmacy/Infection, Imperial College Healthcare NHS Trust, London, UK 5 University Hospitals Plymouth NHS Trust, Plymouth, UK 6 University Hospitals Bristol and Weston NHS Trust, Bristol, UK 7 Department of Infectious Diseases, Queen Elizabeth University Hospital, Glasgow, UK 8 British Society for Antimicrobial Chemotherapy, Birmingham, UK 9 Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Queensland, Australia 10 Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia 11 Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France Correction notice The licence for this paper has been changed to Open Access since it was first published. Acknowledgements The authors thank B Braun Medical Ltd and Vygon (UK) Ltd for funding and in-kind provision of elastomeric devices. FBS acknowledges support from an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (APP1197866). JR acknowledges funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP2007007) and an Investigator Grant (APP2009736) as well as an Advancing Queensland Clinical Fellowship. Contributors Study design (FBS, FD, CJ, TH, MG, MS, RAS, JR), experiment (FBS), sample assay (SW), data analysis (FBS, FD, CJ), draft manuscript (FBS), critical review (FBS, CJ, TH, MG, MS, RAS, FD, JR). FBS is guarantor. Funding This study was funded by BSAC and unrestricted grant contributions from B Braun Medical Ltd and Vygon (UK) Ltd. Competing interests None declared. Patient consent for publication Not applicable. Ethics approval Not applicable. Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non- commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. ORCID iD Fekade Bruck Sime http://orcid.org/0000-0003-4061-2063 REFERENCES 1 Baltimore RS. Acyclovir therapy for herpesvirus infections. Yale J Biol Med 1990;63:261–2. 2 Scheifele D. Acyclovir for intravenous use. Can Med Assoc J 1984;131:1045–6. 3 van der Meer JW, Versteeg J. Acyclovir in severe herpes-virus infections. Am J Med 1982;73:271–4. 4 Wei Y-P, Yao L-Y, Wu Y-Y, et al . Critical review of synthesis, toxicology and detection of acyclovir. Molecules 2021;26:6566. 5 Steingrimsdottir H, Gruber A, Palm C, et al . Bioavailability of aciclovir after oral administration of aciclovir and its prodrug valaciclovir to patients with leukopenia after chemotherapy. Antimicrob Agents Chemother 2000;44:207–9. 6 Solomon T, Michael BD, Smith PE, et al . Management of suspected viral encephalitis in adults--Association of British Neurologists and British Infection Association national guidelines. J Infect 2012;64:347–73. 7 Harris JB, Holmes AP. Neonatal herpes simplex viral infections and acyclovir: an update. J Pediatr Pharmacol Ther 2017;22:88–93. 8 Touzard Romo F, Resnick B, Perez-Cioe M, et al . Outpatient parenteral antibiotic therapy in an academic practice in Rhode Island. R I Med J (2013 ) 2014;98:38–42. 9 Tice AD, Rehm SJ, Dalovisio JR, et al . Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis 2004;38:1651–72. 10 Gupta VD, Pramar Y, Bethea C. Stability of acyclovir sodium in dextrose and sodium- chloride injections. J Clin Pharm Ther 1989;14:451–6. 11 Zhang Y, Trissel LA, Martinez JF, et al . Stability of acyclovir sodium 1, 7, and 10 mg/mL in 5% dextrose injection and 0.9% sodium chloride injection. Am J Health Syst Pharm 1998;55:574–7. 12 Dewulf J, Galanti L, Godet M, et al . Long-term stability of acyclovir in 0.9% NaCl infusion polyolefin bags at 5±3°C after freeze-thaw treatment: a generic product versus the brand name. Ann Pharm Fr 2015;73:108–13. 13 Legeron R, Bougueon G, Berroneau A, et al . Long-term physicochemical stability of acyclovir 5 mg/mL solution stored in polypropylene bags as a simulated hospital stock preparation. Am J Health Syst Pharm 2021;78:806–12. 14 Perks SJ, Robinson N, Pain T, et al . Extended duration infusion temperatures in the tropics: 2 (EDITT2). Pharmacy Practice Res 2018;48:423–30. 10.1002/jppr.1422 Available: https://onlinelibrary.wiley.com/toc/20552335/48/5 15 NHS. A Standard Protocol for Deriving and Assessment of Stability Part 1- Aseptic Preparations (Small Molecules) . NHS Pharmaceutical Research and Development Working Group, 2019. Available: chrome-extension:// efaidnbmnnnibpcajpcglclefindmkaj/https://www.sps.nhs.uk/wp-content/uploads/ 2013/12/Stability-part-1-small-molecules-5th-Ed-Sept-19.pdf 16 Mulabagal V, Annaji M, Kurapati S, et al . Stability-indicating HPLC method for acyclovir and lidocaine in topical formulations. Biomed Chromatogr 2020;34:e4751. 17 Huidobro AL, Rupérez FJ, Barbas C. LC methods for acyclovir and related impurities determination. J Pharm Biomed Anal 2005;37:687–94. 18 USP. Particulate matter in injections 2016. 2023. Available: https://www.usp.org/sites/ default/files/usp/document/harmonization/gen-method/q09_pf_ira_33_2_2007.pdf [Accessed 20 Feb 2023]. 19 Mason WJ, Nickols HH. Crystalluria from acyclovir use. N Engl J Med 2008;358:e14. 20 FDA. ZOVIRAX (Acyclovir sodium) for injection; 2023. Available: https://www. accessdata.fda.gov/drugsatfda_docs/label/2019/018603s030lbl.pdf 21 Yildiz C, Ozsurekci Y, Gucer S, et al . Acute kidney injury due to acyclovir. CEN Case Rep 2013;2:38–40. 22 Perazella MA. Crystal-induced acute renal failure. Am J Med 1999;106:459–65. 23 EMC. Aciclovir 25 mg/ml concentrate for solution for infusion. 2020. Available: https:// www.medicines.org.uk/emc/product/11531/smpc 24 Infusion Nurses Society. Infusion nursing standards of practice. J Infus Nurs 2006;29:S1–92.
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