Original research
Evaluation of the stability of aciclovir in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy Fekade Bruck Sime , 1 Steven Wallis, 1 Conor Jamieson, 2 Tim Hills, 3 Mark Gilchrist, 4 Mark Santillo, 5,6 R Andrew Seaton, 7 Felicity Drummond, 8 Jason Roberts, 1,9,10,11 on behalf of the BSAC OPAT Drug Stability Testing Programme
ABSTRACT Objectives To investigate the stability of aciclovir solutions in elastomeric devices used for outpatient parenteral antimicrobial therapy (OPAT). Methods Triplicates of two elastomeric devices, Accufuser and Easypump II, were filled with a solution of 200 mg, 2400 mg, and 4500 mg aciclovir in 240 mL 0.9% w/v saline. Devices were stored at room temperature for 14 days, followed by 24 hours storage at 32°C. Assessment using a stability indicating assay, pH and subvisible particle analysis was undertaken at 11 time points throughout the study. Results Aciclovir solution at 200 mg and 2400 mg in 240 mL was stable for 14 days at room temperature (<20°C) and 24 hours of 32°C ’in-use’ temperature exposure, remaining above the 95% limit for NHS stability protocols. The high dose was also stable for 14 days at room temperature, but when stored at 32°C there was precipitation of aciclovir within 4 hours in both devices. The precipitate was confirmed as aciclovir and precipitation was not a sign of chemical degradation. Conclusions Aciclovir concentrations above 2400 mg/240 mL are liable to precipitation and cannot be recommended for OPAT services because of heightened risks of nephrotoxicity. Aciclovir solution can be given as a continuous 24-hour infusion for OPAT services at a concentration range of 200–2400 mg in 240 mL in Accufuser and Easypump II elastomeric devices following 14 days storage at room temperature, protected from light. INTRODUCTION Aciclovir is an antiviral drug introduced in 1982 as a topical agent and later in 1983 for intravenous (IV) treatment of herpes virus infections. 1 It can be used to treat infections caused by herpes simplex virus (HSV), varicella-zoster virus and Epstein- Barr virus. 2 3 Structurally, it is a guanine nucleoside analogue and therefore serves as a false substrate in the synthesis of viral DNA, effectively blocking the synthesis of viral DNA and the proliferation of the virus. 4 Aciclovir is available in various dosage forms including topical preparation, oral formulations and IV solution or powder for injection. Oral aciclovir has a limited use and efficacy due to poor bioavail- ability. 5 Currently, IV aciclovir remains the gold standard for the treatment of HSV encephalitis,
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where treatment duration is at least 2 weeks, 6 and for congenital HSV infections in neonates. 7 Outpatient parenteral antimicrobial therapy (OPAT) programmes are designed to support early hospital discharge for patients requiring parenteral therapy, which extends beyond the patient’s need to otherwise remain in hospital. As such, OPAT has been used to effectively complete IV aciclovir therapy in clinically improving patients with HSV encephalitis. 8 9 However, there are limited data on aciclovir stability in the OPAT setting. Despite this, continuous infusion of IV aciclovir is currently being used in OPAT. 8 Data from non-OPAT condition stability studies suggest aciclovir is stable without any significant loss of potency when reconstituted in 5% dextrose or 0.9% sodium chloride solution at a concen- tration of 5 mg/mL at 5°C and 25°C for up to 37 days. 10 However, an icy white precipitation of aciclovir was observed at 5°C which re-dissolved when the temperature was brought to 25°C. A later study 11 tested aciclovir stability at low (1 mg/ mL), intermediate (7 mg/mL) and high (10 mg/mL) concentrations using 5% dextrose or 0.9% sodium WHAT IS ALREADY KNOWN ON THIS TOPIC ⇒ There are limited data on aciclovir stability in the outpatient parenteral antimicrobial therapy (OPAT) setting. Despite this, continuous infusion of IV aciclovir is currently being used in OPAT. WHAT THIS STUDY ADDS ⇒ Aciclovir solution at 200 mg and 2400 mg in 240 mL was stable for 14 days at room temperature (<20°C) and 24 hours of 32°C ‘in- use’ temperature exposure. ⇒ High concentration of aciclovir (4500 mg/240 mL) massively precipitates when exposed to OPAT ‘in-use’ temperature of 32°C. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY ⇒ In the concentration range of 200 mg/240 mL to 2400 mg/240 mL, aciclovir solution in saline is stable, allowing the use of continuous aciclovir infusion in OPAT services. ⇒ Precipitation of aciclovir at the highest concentration tested (4500 mg/240 mL) at 32°C would preclude its use in any clinical setting.
Correspondence to Dr Fekade Bruck Sime, The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia; f.sime@uq.edu.au Received 29 March 2023 Accepted 7 November 2023 EAHP Statement 3: Production and
Compounding. EAHP Statement 4: Clinical Pharmacy Services.
To cite: Sime FB, Wallis S, Jamieson C, et al . Eur J Hosp Pharm Epub ahead of print: [ please include Day Month Year]. doi:10.1136/ ejhpharm-2023-003784 © European Association of Hospital Pharmacists 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.
Sime FB, et al . Eur J Hosp Pharm 2023; 0 :1–6. doi:10.1136/ejhpharm-2023-003784
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