Emergency preparation of sodium sulfadiazinate injection: case report

Objective
Generally harmless in immunocompetent patients, toxoplasmosis can have serious consequences in immunocompromised patients. If not treated promptly, mortality in HSC allograft patients can range from 60 to 100%. Our Production department was asked by a hematologist-transplanter to prepare an emergency parenteral formulation of sulfadiazine for a patient presenting with acute GVH, making the oral route totally unavailable. A parenteral formulation of sulfadiazinate had been developed in-house as a lyophilisate around 1990, but had not been used since. To manage this patient, we prepared an extemporaneous injectable formulation of sodium sulfadiazinate 100 mg/ml, adapting the manufacturing process to the emergency situation.

Method
Preparation is carried out in a controlled atmosphere, using a validated method to dissolve sulfadiazine with a solution of NaOH 10N ad pH 9.9. The final solution contains 0.02% sodium metabisulfite and is packaged in sterile 10 ml vials. It is produced by sterilizing filtration after 5 µm pre-filtration. The final solution was checked for pH and osmolality. Given the urgency of the request, it was not possible to freeze-dry the preparation, nor to quarantine it. Visual inspection of the injectable solution was carried out, and the endotoxin content was analyzed on both the raw material and the finished product (ʎ = 0.1 EU/mg). A double sample was taken for bacteriological testing in accordance with the Pharmacopoeia and for early detection of microbiological contamination by the Microbiology Department. Vials were issued as and when clinically required, and always after verification of the absence of contamination in the samples taken.

Results
At the end of the incubation periods, no contamination was detected. The patient received 1.5 g sulfadiazinate 4 times a day for 16 days, and tolerated the treatment well. Once the acute GVH was under control, the patient was switched to the oral form.

Discussion
The aim of the Production department is to meet the needs of the medical profession by making available safe and effective preparations that do not exist on the Belgian market. This experience is just one of many, but it still bears witness to the indispensable role played by pharmacists in developing medicines for their patients, and to their interaction with the hospital’s various specialists. Furthermore, for the pharmacist in charge of production, it is imperative to consider the possibility of stepping outside the strict regulatory framework when clinical requirements precipitate the usual course of his or her practice. In all cases, this can only be done by doing everything possible to guarantee optimal results for the patient.

See the poster