Article Text

PDF
Investigations into the physical and chemical stability of concentrated co-trimoxazole intravenous infusions
  1. Israa Khaleel1,
  2. Syed Tabish R Zaidi1,2,
  3. Madhur D Shastri3,
  4. Mathew Suji Eapen1,
  5. Long Chiau Ming1,4,
  6. Troy Wanandy1,2,
  7. Rahul P Patel1
  1. 1 School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
  2. 2 Pharmacy, Royal Hobart Hospital, Hobart, Tasmania, Australia
  3. 3 School of Health Sciences, University of Tasmania, Hobart, Tasmania, Australia
  4. 4 School of Pharmacy, KPJ Healthcare University College, Nilai, Negeri Sembilan, Malaysia
  1. Correspondence to Dr Rahul P Patel, Division of Pharmacy, School of Medicine, University of Tasmania, Hobart, Tasmania 7005, Australia; Rahul.Patel{at}utas.edu.au

Abstract

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 An aliquot was withdrawn immediately (at 0 hour) and after 0.5, 1, 2 and 4 hours of storage for high-performance liquid-chromatography (HPLC) analysis, and additional samples were withdrawn every half an hour for microscopic examination.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 380 mL of glucose 5% solution (1:20 v/v) and for 2 hours when diluted with 280 mL glucose 5% solution (1:15 v/v).

  • Trimethoprim
  • Sulfamethoxazole
  • Stability And Incompatibility
  • High Performance Liquid Chromatography
  • Pneumocystis Jiroveci Pneumonia

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.