Stability of drug additives to peritoneal dialysate

OBJECTIVE: The primary literature was reviewed to determine the stability of drug additives in peritoneal dialysis solutions. DATA SOURCES: A MEDLINE search and retrieval, covering the period 1981 to 1994, was undertaken to identify relevant original literature. Additional references were identified from citations within the original literature. Non-English literature was excluded unless an English abstract was provided. STUDY SELECTION: Forty-nine studies were identified. Of these, 24 were directly related to drug stability, 13 were related to the clinical use of the drug additives but included no stability data, and 12 examined other, nonstability aspects of in vitro activity of antibiotics, additives, or drug adsorption in peritoneal dialysis bags and tubing. DATA EXTRACTION: Data included concentrations of drug additives and dialysate solutions, duration and temperatures of storage conditions, types of assay, and whether they were stability-indicating. RESULTS: Stability was defined as the duration of time that the drug concentration remained at 90% or more of the original concentration. Stability was examined under a large variety of conditions. Thirty-one drugs were identified from 20 manuscripts as single-drug additives. Most beta-lactams were stable for 1-2 weeks in a refrigerator and for several days at room temperature. Aminoglycosides were stable for 1-2 days at room temperature. Glycopeptides were stable for several weeks refrigerated or at room temperature. Prolonged storage at room temperature resulted in instability of cefotaxime, ceftazidime, ceftriaxone, and miconazole. Eleven drugs were identified from seven manuscripts as drug combination studies and showed similar stability as single agents. Dialysate concentration appeared to have minimal effect on stability. CONCLUSIONS: Drug additives in peritoneal dialysate, singly or combined, should be avoided unless data are available to support their stability. Additives should be made as close as possible to the time of the exchange. Alternatively, additives should be stored refrigerated, then warmed prior to use. The practice of preparing numerous bags at one time should be avoided. Finally, stability data do not indicate sterile integrity of the dialysate.