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Investigations into the physical and chemical stability of concentrated co-trimoxazole intravenous infusions

journal contribution
posted on 2023-05-19, 08:21 authored by Khaleel, I, Syed Razi ZaidiSyed Razi Zaidi, Madhur ShastriMadhur Shastri, Mathew Eapen, Ming, LC, Stephanus WanandyStephanus Wanandy, Rahul PatelRahul Patel

Objectives: High dose of intravenous sulfamethoxazole and trimethoprim (co-trimoxazole) is often used in immunocompromised patients for the treatment of Pneumocystis jiroveci pneumonia. Current manufacturer’s dilution recommendation for intravenous co-trimoxazole (1:25 v/v) requires the administration of 2 L of additional fluid per day causing serious complications including pulmonary oedema. Intravenous administration of concentrated solution of co-trimoxazole may minimise the risk of fluid overload associated side effects. Therefore, the objective of the study was to investigate the physicochemical stability of concentrated intravenous co-trimoxazole solutions.

Methods: Four ampoules of intravenous co-trimoxazole were injected into an infusion bag containing either 480 (1:25 v/v), 380 (1:20 v/v), 280 (1:15 v/v) or 180 (1:10 v/v) mL of glucose 5% solution. Three bags for each dilution (total 12 bags) were prepared and stored at room temperature. An aliquot was withdrawn immediately (at 0 hour) and after 0.5, 1, 2 and 4 hours of storage for high-performance liquid-chromatography (HPLC) analysis, and additional samples were withdrawn every half an hour for microscopic examination. Each sample was analysed for the concentration of trimethoprim and sulfamethoxazole using a stability indicating HPLC method. Samples were assessed for pH, change in colour (visually) and for particle content (microscopically) immediately after preparation and on each time of analysis.

Results: Intravenous co-trimoxazole at 1:25, 1:20, 1:15 and 1:10 v/v retained more than 98% of the initial concentration of trimethoprim and sulfamethoxazole for 4 hours. There was no major change in pH at time zero and at various time points. Microscopically, no particles were detected for at least 4 hours and 2 hours when intravenous co-trimoxazole was diluted at 1:25 or 1:20 and 1:15 v/v, respectively. More than 1200 particles/ mL were detected after 2.5 hours of storage when intravenous co-trimoxazole was diluted at 1:15 v/v.

Conclusions: Intravenous co-trimoxazole is stable over a period of 4 hours when diluted with 380mL of glucose 5% solution (1:20 v/v) and for 2 hours when diluted with 280mL glucose 5% solution (1:15 v/v).


Publication title

European Journal of Hospital Pharmacy






School of Pharmacy and Pharmacology


BMJ Publishing Group

Place of publication

United Kingdom

Rights statement

Copyright 2017 European Association of Hospital Pharmacists (unless otherwise stated in the text of the article)

Repository Status

  • Restricted

Socio-economic Objectives

Public health (excl. specific population health) not elsewhere classified

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